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Incidence
rates for esophageal adenocarcinoma (EA) have risen steeply in the
United States and other Western countries during the past 30 years.
Among white men in the United States, the increases have outpaced
those for any other cancer, although rates have risen substantially
in other groups as well.
Investigators have been able to identify a few moderately strong
risk factors for EA and its precursor—Barrett’s esophagus—including
tobacco use, obesity, and gastroesophageal reflux. However, progress
in research on this cancer has been limited. “Because this cancer
has been relatively uncommon, many of the studies, at east the first-generation
investigations, involved small numbers of subjects and an even smaller
subset of subjects who provided biospecimens,” said Wong-Ho
Chow, Ph.D., of the Occupational and Environmental Epidemiology
Branch. One approach to surmounting the problem of small numbers is
the formation of a consortium—a voluntary network of scientists
who have agreed to cooperative research efforts to enable the sharing
of ideas, data, tools, and specimens across population-based studies.
One approach to surmounting the
problem of small numbers is the formation of a consortium—a
voluntary network of scientists who have agreed to cooperative research
efforts to enable the sharing of ideas, data, tools, and specimens
across population-based studies.
Building a foundation for the new Barrett’s Esophagus and Adenocarcinoma
Consortium (BEACON) was the topic of a workshop held at the NCI on
May 9 and 10, 2005, with support provided by the NIH Office of Rare
Diseases. Planned by Dr. Chow, Dr. Olof Nyrén of the Karolinska
Institutet in Stockholm, and Dr. Thomas Vaughan of the Fred Hutchinson
Cancer Research Center in Seattle, the workshop was attended by more
than three dozen scientists from the United States, Europe, and Australia.
It represented the start of collaborative efforts among researchers
dedicated to the study of Barrett’s esophagus and EA.
During the workshop, principal investigators from 14 separately funded
case-control studies outlined the types of data and biospecimens available,
described the status of ongoing and completed research, and identified
possible avenues for collaborative work. Several laboratory and clinical
investigators gave presentations on state-of-science research approaches
that may be applied to these tumors. Dr. Daniela Seminara (Division
of Cancer Control and Population Sciences) and Dr. Ernest Hawk (Division
of Cancer Prevention) of NCI, as well as Dr. Frank Hamilton and Dr.
Jay Everhart of the National Institute of Diabetes and Digestive and
Kidney Diseases, provided information about possible sources of support
for the consortium’s activities. Some participants spoke about
their experiences with other consortia. Stephen Chanock, M.D.,
described the resources available through NCI’s Core Genotyping
Facility for high-throughput genotyping in support of BEACON’s
efforts.
The second day of the workshop was devoted to developing an organizational
framework for BEACON, which will consist of four working groups and
a steering committee. Plans were made to develop short-term, intermediate,
and long-term projects. Consortium members agreed to communicate regularly
by teleconference and other means before meeting again in the spring
of 2006.
—Wong-Ho Chow, Ph.D., and Karen Eddleman
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In May, DCEG held its fifth
annual Careers in Epidemiology Seminar. This annual event is offered
to help the approximately 75% of DCEG fellows who take positions outside
of the Division at the end of their fellowships. Organized by Shelia
Hoar Zahm, Sc.D., DCEG Deputy Director, the series of seminars
involves DCEG alumni, who inform fellows of opportunities in other
settings and offer practical advice on how to find and negotiate for
these jobs. This year’s speakers were Dr. Allen E. Bale, Associate
Professor of Genetics and Director of the DNA Diagnostic Laboratory
and the Cancer Genetics Program at Yale University School of Medicine;
Dr. Ahmedin Jemal, Department of Epidemiology and Surveillance Research,
American Cancer Society (ACS); and Dr. Deborah M. Winn, Chief of the
Clinical and Genetic Epidemiology Research Branch, NCI Division of
Cancer Control and Population Sciences (DCCPS).
During
his years at NCI, Dr. Bale received training in genetics and epidemiology
in DCEG as well as in the Laboratory of Biochemistry in the Center
for Cancer Research. He spoke to the fellows on the challenges and
rewards of shaping an interdisciplinary research program. He encouraged
them to establish a research area that they could develop further
as a junior faculty member and to identify and pursue the type of
job they want. When considering a position, he advised them to ensure
that the institution has the type of core facilities they would need,
to compare graduate and medical schools in terms of tenure requirements
and access to students, and to evaluate all aspects of start-up packages
including salary; benefits; number of years of “protected time”
for research; and funds for supplies, equipment, and personnel. He
stressed the importance of keeping focused on the work needed to be
successful.
Dr. Jemal has continued the descriptive epidemiology research in
which he trained at DCEG in his work on cancer surveillance activities
at ACS. The ACS tracks cancer incidence, mortality, and survival,
as well as trends in cancer risk factors and use of screening tests.
Dr. Jemal’s annual reports on U.S. cancer statistics are among
the most frequently cited papers in biomedical journals. He described
the power of descriptive epidemiology to generate interesting clues
to cancer etiology and the development of new statistical methods
to increase the accuracy of projections.
After Dr. Winn’s postdoctoral fellowship in DCEG, she worked
at the National Center for Health Statistics and the National Institute
of Dental and Craniofacial Research before returning to NCI as Program
Director and Branch Chief in DCCPS. Each of these positions enhanced
her scientific, technical, and practical skills. She described the
satisfaction a program director can enjoy from working with extramural
investigators to foster their research, helping to move cancer epidemiology
forward by contributing to the scientific agenda in cancer epidemiology,
identifying priorities for the Institute, developing infrastructure,
and participating in team science and research consortia. She emphasized
that leading and participating in scientific teams is a key and growing
part of cancer epidemiology. She encouraged the fellows to take full
advantage of the various types of training opportunities available
to them, including topics such as media training.
Fellows can also find many useful references on career development,
interviewing, negotiating, scientific management, and mentoring in
the DCEG Office of Education library, located outside EPS 3048 and
organized by Kristin Kiser, M.H.A.
—Shelia Hoar Zahm, Sc.D.
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To
provide more competitive funding opportunities for fellows and tenure-track
scientists and to encourage innovative, interdisciplinary research,
DCEG recently expanded its Intramural Research Award (IRA) program
to include a spring and fall cycle. In each cycle, up to three proposals
will be funded.
The winners of the spring 2005 competition are James Lacey,
Ph.D., of the Hormonal and Reproductive Epidemiology Branch
(HREB), for his proposal on “PTEN tumor suppressor gene
alterations in the progression from endometrial hyperplasia to carcinoma”;
Ola Landgren, M.D., Ph.D., of the Genetic Epidemiology
Branch, for his project on “Familial, epidemiologic, and biologic
features of monoclonal gammopathy of underdetermined significance”;
and Lindsay Morton, Ph.D. (HREB), for her proposal
entitled “Defining molecular subtypes of lymphoma for relevance
to etiology, diagnosis, and survival.”
The IRA proposals were reviewed by members of the NCI Board of Scientific
Counselors or other extramural scientists with appropriate expertise,
along with senior DCEG scientists. The proposals were judged with
respect to their potential for significant scientific or public health
impact, innovative aspects of approach or methodology, interdisciplinary
or collaborative nature, ability to achieve the objectives within
the proposed time frame and resources, and programmatic relevance
to Division and Institute priorities.
—Sandy Rothschild
ANNUAL SURVEY OF BRANCH AND DIVISON
MANAGEMENT
The DCEG Committee of
Scientists (COS) conducts an annual survey of Branch and Division
management that is critical to maintaining an optimal research
environment. COS was created in 1995 to identify and promote
practices that enhance scientific life in the Division and to
advise the DCEG Director on issues such as communication, removing
administrative obstacles to productive research, and career
development. Following its inception, COS immediately recognized
a need for a bidirectional approach to performance review, since
the success of DCEG’s mission depends not only on the
productivity of the scientific staff but also on the management
skills and practices at the Branch and Division levels. The
DCEG Annual Survey of Branch and Division Management was the
product of that early COS vision.
The survey has
become an essential component of the ongoing dialogue between
Division leadership and staff, who are devoted to achieving
the DCEG vision of scientific excellence.
The annual survey is designed to allow staff an opportunity
to provide candid assessment of issues that affect Branch and
Division management and to suggest constructive approaches to
enhance the scientific environment in DCEG. Many of the issues
raised in a recent survey (e.g., how to attract and retain a
scientific staff of distinction, how to improve management of
shared Division resources during times of budget constraints)
formed the agenda for extended discussion at a Senior Advisory
Group Retreat, while several other issues were targeted for
action in ensuing months. Survey results are an important part
of the Division Director’s annual human resource planning
meetings with Branch Chiefs.
COS employs several strategies to protect the confidentiality
of staff members, such as delinking responses from each participant’s
e-mail address and position. Only the Division Director and
Deputy Director view verbatim comments pertaining to Branch
management, while the COS chair also reviews responses that
address Division-wide issues. Because the survey is essentially
a management tool, not a typical epidemiologic data collection
instrument, COS has increasingly used open-ended questions designed
to elicit narrative comments. COS representatives welcome content
and formatting suggestions as well as questions about any facet
of the survey (http://intranet.dceg.cancer.gov/committees/cos/cosmembers).
The survey has become an essential component of the ongoing
dialogue between Division leadership and staff, who are devoted
to achieving the DCEG vision of scientific excellence.
—Mary Lou McMaster, M.D.
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Non-participation
appears to be a growing problem in the field of epidemiology, threatening
confidence in research results. At the recent Joint Meeting of the
Society for Epidemiologic Research (SER) and the Canadian Society
for Epidemiology and Biostatistics in Toronto, Patricia Hartge,
Sc.D., Deputy Director of the Epidemiology and Biostatistics
Program, organized and spoke at a scientific session dedicated to
the issue. In her talk, “How big is the problem and what is
the solution?” she said, “Epidemiologists must consider
the effect of non-participation on self-selection and misclassification
bias in our studies, not only during analysis and publication, but
also at the earliest stages of study design and implementation.”
Meeting attendees learned about the related work of two DCEG fellows,
Lindsay Morton, Ph.D., of the Hormonal and Reproductive
Epidemiology Branch, and Jinbo Chen, Ph.D., of the
Biostatistics Branch. Dr. Morton submitted a poster on her survey
of current reporting practices for epidemiologic studies begun between
1970 and 2003. She found that a surprising proportion of published
studies in epidemiology journals did not report any information about
subject participation rates, making it difficult for scientists to
assess and address the extent of the phenomenon across the field,
especially at a time when biospecimen collections are more frequently
a component of participation.“More troubling,” according
to Dr. Morton, “is our discovery that in those studies reporting
sufficient or any response information, participation rates have been
declining for all study designs (see Figure 1). The sharpest declines
occurred within the last decade, especially in case-control studies
and particularly in population control subjects.”
Meeting attendees learned about the related work of two DCEG fellows,
Lindsay Morton, Ph.D., of the Hormonal and Reproductive
Epidemiology Branch, and Jinbo Chen, Ph.D., of the
Biostatistics Branch. Dr. Morton submitted a poster on her survey
of current reporting practices for epidemiologic studies begun between
1970 and 2003. She found that a surprising proportion of published
studies in epidemiology journals did not report any information about
subject participation rates, making it difficult for scientists to
assess and address the extent of the phenomenon across the field,
especially at a time when biospecimen collections are more frequently
a component of participation.“More troubling,” according
to Dr. Morton, “is our discovery that in those studies reporting
sufficient or any response information, participation rates have been
declining for all study designs (see Figure 1). The sharpest declines
occurred within the last decade, especially in case-control studies
and particularly in population control subjects.”
In a session on “Bias: Methodological and practical considerations,”
Dr. Chen presented her biostatistical analysis entitled, “Quantifying
selection bias in epidemiologic studies,” which showed that
in case-control studies, the ratio of exposed and non-exposed cases
and controls who are non-responsive, rather than simply the overall
level of non-response, determines the extent of bias.
In related work, the first study to look at the relationship between
genetics and non-response was conducted by Parveen Bhatti,
M.S., of the Radiation Epidemiology Branch (REB). Mr. Bhatti
analyzed single nucleotide polymorphism genotypes, haplotypes, and
short tandem repeats (STRs) among control groups rom three DCEG studies.
Among 2,955 individuals, he compared 108 genotypes, 8 haplotypes,
and 9 to 15 STRs by respondent type. He concluded that “there
was little evidence to suggest that genetic characteristics relate
to willingness to respond,” adding, “This was just the
first set of genes examined.”
The summary of Dr. Hartge’s session will appear as a commentary
in an upcoming issue of Epidemiology. Dr. Morton’s
study will appear in the American Journal of Epidemiology;
Dr. Chen’s will be submitted later this year; and Mr. Bhatti’s
research will appear in Cancer Epidemiology, Biomarkers & Prevention.
In addition, Cecile Ronckers, Ph.D. (REB), identified
factors affecting questionnaire response in a cohort study published
in the Annals of Epidemiology in 2004.
—Alyssa Voss Minutillo, M.P.H.
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NCI hosted a workshop from
July 18 to 20 on “Best practices for establishing and maintaining
biorepositories that support cancer research.” The workshop
was the second in a series organized by the NCI Biospecimen Coordinating
Committee (BCC). The first meeting, which concerned ethical, legal,
and policy issues relevant to NCI biorepositories, was held from June
23 to 24. The workshops shared an overall mission of identifying and
recommending best practices for the establishment and maintenance
of human biospecimen repositories designed to broadly support cancer
research and development.
The July workshop was chaired by Dr. Anna Barker, NCI Deputy Director
for Advanced Technologies and Strategic Partnerships, and Dr. Mark
Rubin of the Dana-Farber Cancer Institute. Jim Vaught, Ph.D.,
DCEG Office of the Director (OD), and Dr. Julie Schneider, NCI OD,
co-chaired the BCC subcommittee that developed the workshop agenda.
Marianne Henderson, M.S., Chief of the DCEG Office
of Division Operations and Analysis, also served on the BCC subcommittee.
Neil Caporaso, M.D., of the Genetic Epidemiology
Branch, Montserrat Garcia-Closas, M.D., Dr.P.H.,
of the Hormonal and Reproductive Epidemiology Branch, Patricia
Hartge, Sc.D., Deputy Director of the Epidemiology and Biostatistics
Program (EBP), and Robert Hoover, M.D., Sc.D., Director
of EBP, were among the more than 100 workshop participants.
In her opening remarks, Dr. Barker noted that biospecimens represent
the future of personalized medicine. NCI’s biorepositories support
not only individual investigators, but also many of the NCI’s
strategic initiatives, including:
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The NCI cancer Biomedical Informatics Grid (caBIG);
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A national clinical proteomics technology initiative
to provide common infrastructure and standardization;
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A forthcoming collaborative pilot program with the
National Human Genome Research Institute to lay the groundwork for
sequencing cancer genomes;
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The Alliance for Nanotechnology in Cancer to catalyze
development of technologies and products that can interact with
and interrogate cells for diagnosis and treatment.
The workshop agenda addressed biorepository practices from several
perspectives, including basic, population, and clinical sciences,
as well as the patient’s perspective. Plenary sessions addressed
cross-cutting issues, such as quality control and bioinformatics,
as well as the variety of analytical methods applied to biorepository
specimens.
The first of two working group sessions addressed best practices
according to specimen type (blood, tissue, and other) as well as bioinformatics
and quality control/quality assurance practices. The second working
group session addressed a new proposal for evaluating and monitoring
the quality of NCI biorepositories. The working group reports highlighted
many areas of agreement on best biorepository practices and called
for additional research into unresolved issues, such as optimal specimen
collection methods that maximize stability for different types of
laboratory analyses.
Recommendations
developed by the workshop discussions were presented in September
to the National Cancer Advisory Board and will be made available for
public comment later in the year. In June, Dr. Carolyn Compton joined
NCI as the Director of Biorepositories and Biospecimen Research. She
will establish a biorepository science research program to follow
up on these recommendations.
—Marianne Henderson, M.S., and Jim Vaught, Ph.D.
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Computerized
study management systems are an integral part of conducting clinical
research protocols in the Clinical Genetics Branch (CGB) and the Genetic
Epidemiology Branch (GEB). The Family and Individual Registry Event
Management (FAIR-EM) System provides a secure Web interface that allows
users to track the status of study subjects’ day-to-day study-related
events and information as they move through the pre-clinic, clinic,
post-clinic, and follow-up phases of a study. Investigators from CGB
and GEB, working with contractors from Information Management Services,
Inc., and Westat, Inc., designed a tool that can be inexpensively
and quickly adapted to the data collection and clinic scheduling requirements
of any new study. Although FAIR-EM was designed with the needs of
family studies research in mind, the system template is adaptable
to other types of studies as well.
Each study within the current system has its own set of participant
and event data fields and system-enforced rules for determining participant
enrollment and event eligibility. Users may add, update, and view
the status of each subject’s completion of study events. When
a defined event status is modified, the system generates and/or modifies
other events for that participant as specified for the study. FAIR-EM
users may search for participants and events through an interface
that includes all database fields within a study. The interface allows
users to choose which fields they want displayed in the search results.
One of the most important features of this system is interactive
data entry, which provides an efficient and accurate means to monitor
all aspects of data collection. The resulting computer files generated
from the study management system facilitate rapid, up-to-date report
generation. Study events and their outcomes are scheduled and recorded
in accordance with each study’s standard operating procedures.
The events that are typically monitored using FAIR-EM include:
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Recruitment phone calls and letters;
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Status of informed consent;
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Scheduling of clinic visits;
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Acquisition of biological specimens;
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Performance of study-related tests and procedures;
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Completion of questionnaires and other data collection
instruments;
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Requests for medical records and pathology;
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Mailing of participant “thank you”
letters.
Reports can include the number of participants who are active, completed,
or withdrawn from a study; the number of participants who have been
evaluated; the number of follow-up studies required; and the number
of adverse events that have occurred to participants in a study.
Each study schedule records interim and final disposition for each
individual participant. Triggers and rules that are specific to a
study schedule help determine the individuals who are eligible for
each study step. This process identifies patients who need to be scheduled
for future encounters and helps users keep track of each protocol-related
component as it is completed.
Administrative reports provide information on events that are outstanding
and stages that are anticipated in the near future. Summary reports
allow the study team to monitor the progress of the study by viewing
event statistics across the cohort or in cohort sub-groups. These
reports also provide information required by study monitoring agencies
and institutional review boards (IRBs).
FAIR-EM was initially implemented to support CGB’s Breast Imaging
study and then modified for use in the Familial Testicular Cancer
project. This conversion was accomplished at a fraction of the time
and cost that would have been required to build a new study management
tool de novo. FAIR-EM can be adapted to meet changing study
requirements and for new studies quickly, efficiently, and at a relatively
low cost. For further details, see the DCEG Tools section.
—Jennifer Loud, M.S.N., C.R.N.P., and Mark Greene,
M.D.
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A
problem solver by nature, tenure-track investigator Ruth Pfeiffer,
Ph.D., of the Biostatistics Branch (BB), works closely with
other researchers at DCEG, the Karolinska Institute in Stockholm,
George Washington University, Mulago Hospital in Kampala, Uganda,
and elsewhere.
“I like to work with people to find solutions to challenging
scientific problems,” she said. “My passion for problem
solving probably comes from my engineering background.” The
results of her collaborations and innovative statistical approaches
have led to important findings—some of which have run counter
to widely accepted thinking.
Dr. Pfeiffer earned a master’s degree in applied mathematics
(computer science) in her native country of Austria. She came to the
United States when she received a Fulbright Fellowship to study applied
statistics in 1992–1993, and she subsequently earned a doctorate
in mathematical statistics from the University of Maryland in 1998.
She recalled, “When I took a summer course on statistical genetics
at the University of North Carolina, I really became interested in
biological applications. The genome project was starting to yield
a tremendous amount of genetic information. I wanted to work with
genetic data, because I knew it would open up a world of research
opportunities.” She joined the NCI as a fellow in 1999 and became
a tenure-track investigator in 2001.
One major focus of Dr. Pfeiffer’s research is genetic epidemiology.
Jointly with Mitchell Gail, M.D., Ph.D., Chief of
BB, she developed a random effects model to analyze family-based studies
of cancer and assess associations with environmental and genetic factors
while accounting for data ascertainment and different familial correlations.
After showing that the model was reasonably robust, she applied it
to a wide variety of datasets.
One example is a family study of nasopharyngeal cancer in Taiwan
with Allan Hildesheim, Ph.D., of the Hormonal and
Reproductive Epidemiology Branch (HREB). The study is investigating
associations with consumption of salted fish during childhood and
other exposures as well as genetic factors. Dr. Pfeiffer has also
teamed up with Maria Teresa Landi, M.D., Ph.D., of
the Genetic Epidemiology Branch (GEB), and extended the random effects
model, combining family and case-control data to analyze the effects
of variants in the melanocortin 1 receptor (MC1R) gene on
melanoma risk.
“It was a challenge to combine these two types of data,”
Dr. Pfeiffer said. “But this approach greatly increased the
power of the study.” In a study with Dr. Bert Zbar of the Center
for Cancer Research (CCR), she is currently assessing risk factors
in families with renal cancer.
The random effects model can be used for a surprisingly wide range
of problems. Working with Dr. Louise Ryan of Harvard University, Dr.
Pfeiffer devised a longitudinal case-cohort design utilizing the same
type of model. Currently, she is comparing the random ways of analyzing
family data.
Dr. Pfeiffer has devised survival methods to detect familial aggregations
of cancer using record-linkage data from Sweden and Denmark. Databases
describing familial relationships are linked to national cancer registries
and are often performed as a preliminary step to case-control or family-based
studies. As Dr. Pfeiffer observed, “Aggregation of cancer in
families provides an important clue that a genetic or environmental
factor is at work.” In a collaborative effort with Lynn
Goldin, Ph.D. (GEB), and researchers at the Karolinska Institute,
she demonstrated significant familial aggregation of Hodgkin lymphoma
and chronic lymphocytic leukemia, and she is examining the familial
risks of other cancers associated with these cancers.
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Dr. Pfeiffer and Sarah Daugherty, M.P.H., a predoctoral
fellow in the Occupational and Environmental Epidemiology Branch,
made a startling discovery attempting to detect “anticipation”
of non-Hodgkin lymphoma. “Anticipation means that a disease
with a genetic component has successively younger ages of onset as
it gets passed from generation to generation.” According to
Dr. Pfeiffer, anticipation “only has a proven molecular mechanism
in Huntington’s disease,” but the phenomenon had been
reported for non-Hodgkin lymphoma in some studies. “By applying
survival methods and correcting for secular trends, such as increasing
incidence in the population, the anticipation effects disappeared.”
Those findings led to a paper published in Cancer Epidemiology,
Biomakers & Prevention. “The take-home lesson is that
if the incidence of a condition changes in the population, then one
must control carefully for those changes before interpreting effects
based on age-of-onset data.”
Dr. Pfeiffer is particularly proud of a finding that arose from another
major reserach focus—models for studying viral disease. She
works closely with Sam Mbulaiteye, M.D., of the Viral
Epidemiology Branch, whose interest is human herpesvirus 8 (HHV-8),
the causative agent of Kaposi sarcoma. “This virus is very interesting,”
Dr. Pfeiffer said. “Its prevalence in Western countries is low
except in patients with acquired immunodeficiency syndrome, but in
Sub-Saharan Africa, it is endemic. However, exact modes of transmission
are not well understood.”
There is some evidence that HHV-8 is blood-borne, which would help
spread the disease to children with sickle cell anemia because they
receive many transfusions. Using Dr. Mbulaiteye’s cross-sectional
data on the transfusion histories of those children, Dr. Pfeiffer
built a Markov model and was able to estimate the probability per
transfusion of becoming infected with HHV-8, even though the serology
data were collected at a single point in time. The model, which allows
for interchild heterogeneity in susceptibility to infection, indicated
that the risk of HHV-8 infection was about 2.6% per transfusion.
What lies ahead for Dr. Pfeiffer? Her newest challenge lies in the
field of high-dimensional molecular data, such as proteomics data
that may be useful in the early detection of cancer. However, no standard
statistical approaches to analyzing these data exist. She has analyzing
these data exist. She has been collaborating with Dr. Efstathia Bura
of George Washington University on applying and extending dimension
reduction and inverse regression techniques to analyze these data.
When she looks to the future, Dr. Pfeiffer foresees even greater reliance
on molecular data to address epidemiologic problems. “We will
also have to learn more about causal pathways to discern interactions
between the environment and genetic factors in the development of
cancer.”
One thing is clear: DCEG is where she wants to continue her work:
“This is a fantastic research environment! I’m extremely
lucky to be here.”
—Karen Eddleman
MIA GAUDET RECEIVES SALLIE ROSEN KAPLAN
FELLOWSHIP
Mia
Gaudet, Ph.D., joined the Hormonal and Reproductive
Epidemiology Branch (HREB) in July as DCEG’s first recipient
of the Sallie Rosen Kaplan (SRK) Fellowship for Women Scientists
in Cancer Research, a competitive program for new women postdoctoral
fellows applying to train in NCI’s Intramural Research
Program. The Foundation for the National Institutes of Health
provides the endowment for the fellowship based on a bequest
from Ms. Kaplan, who was committed to the education and the
professional enhancement of women. The fellowship is awarded
annually to encourage talented young women scientists to pursue
advanced training in cancer research and reward them for demonstrated
excellence in their chosen field. SRK fellows receive augmented
stipends.
Dr. Gaudet, who holds a doctoral degree in epidemiology from
the University of North Carolina at Chapel Hill, is collaborating
with Louise Brinton, Ph.D. (Chief of HREB),
Montserrat Garcia-Closas, M.D., Dr.P.H. (HREB),
and James Lacey, Ph.D. (HREB). Dr. Gaudet was
first exposed to DCEG while serving as a summer research intern
with the Nutritional Epidemiology Branch four years ago. "As
I became more familiar with the work and accomplishments of
DCEG scientists, it strengthened my conviction to come here
when I finished my doctorate," she said.
Dr. Gaudet is investigating a variety of biochemical and molecular
markers in breast and other hormonally related cancers and their
relationships to body mass index and physical activity. Studying
these types of cancers is particularly compelling, according
to Dr. Gaudet: "From a public health standpoint, although we
understand some of the risk factors, as yet there is no ‘smoking
gun’ like there is for tobacco smoking and lung cancer.
That’s why I am intrigued with hormonally related cancers."
Because she holds a bachelor’s degree in nutrition and
has investigated the role of nutrition in health and disease,
Dr. Gaudet hopes to draw upon her background as she investigates
the dietary and nutritional determinants of cancer. "One of
my goals as a postdoctoral fellow," she said, "is to bring together
all these etiologic components: genetics, hormones, and diet."
Specifically, she is interested in gene-nutrient interactions
and the interplay between nutrition and endogenic hormones in
cancer prevention and control.
More information about the fellowship is available from the
Foundation for NIH through its web site (www.fnih.org).
—Karen Eddleman
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Every summer brings the prospect
of introducing cancer epidemiology, genetics, and biostatistics research
to a new cadre of bright and energetic students. This summer 20 students
at academic levels ranging from high school through graduate school
conducted research under the guidance of DCEG mentors.
“I am always impressed with
the knowledge, enthusiasm, and energy the summer fellows bring to
our research program. The posters clearly document the scientific
contributions made by the fellows.”
The Fifth Annual DCEG Summer Poster Session was held on August 5
with 13 students presenting posters to a standing-room-only crowd
of DCEG staff. The students enjoyed discussing their projects with
DCEG scientists, who offered relevant critiques and comments. A senior
investigator in the Occupational and Environmental Epidemiology Branch
(OEEB) and summer mentor, Aaron Blair, Ph.D., said,
“I am always impressed with the knowledge, enthusiasm, and energy
the summer fellows bring to our research program. The posters clearly
document the scientific contributions made by the fellows.”
Many of the students had presented to a large audience at the NIH-wide
Summer Poster Session the day before. Several noted that getting recognition
and feedback from those with experience and authority in their specific
research area made the DCEG event both more challenging and more rewarding.
The poster session was preceded by an awards ceremony and discussion
with Joseph F. Fraumeni, Jr., M.D., DCEG Director,
Shelia Hoar Zahm, Sc.D., DCEG Deputy Director, and
Demetrius Albanes, M.D., Chief of the Office of Education
and Senior Investigator in the Nutritional Epidemiology Branch. Reflecting
on her experience, University of Maryland graduate student Lindsay
Hoskins said, "Working in the Clinical Genetics Branch (CGB)
over the past several months has solidified my interest in continued
work in the medical and biobehavioral field, specifically with regard
to familial cancers. My summer experience has made me more aware of
the challenges and opportunities that exist within this exciting new
field."
This
year DCEG hosted two participants in the highly competitive NCI Introduction
to Cancer Research Careers (ICRC) program, Sheila Thomas,
a master’s student in nursing education at Clemson University,
and Alexis Lebron, a junior majoring in cell biology and genetics at
the University of Maryland. ICRC offers students from diverse and/or
disadvantaged backgrounds an opportunity to work at NCI for a summer;
the awards also include support for summer housing and travel. ICRC
participants are carefully selected by a committee of NCI principal
investigators. For further details, see the ICRC web site ( http://icrc.nci.nih.gov).
Summer student Regan Howard observed, "I thought
the summer experience was a great chance to apply some of the principles
that I’ve learned in school towards a specific project in a
great research environment." Ms. Howard is in her second year in the
M.P.H. program at George Washington University School of Public Health
and Health Services.
Summer applications begin trickling in during the month of November
and become a deluge of interested students from February through the
end of May. Students interested in applying for the summer program
are encouraged to view the DCEG Summer Web page (http://www.dceg.cancer.gov/summer.html),
complete the summary application, and submit a full application to
the NIH Summer Application site (http://www.training.nih.gov/student/index.asp),
indicating their interest in epidemiology at NCI. DCEG received nearly
250 applications this year and accepted 20 students, a proportion
similar to the NIH average.
—Kristin Kiser, M.H.A.
Research Projects by the 2005 Summer
Fellows
Hereditary leiomyomatosis and renal cancer in relation
to mutations in the fumarate hydratase gene.
Eitan Bernstein, Charles E. Smith Jewish Day
School. Mentors: Jorge Toro, M.D., and Ousmane
Toure, Ph.D. (both in GEB)
Elevated risk of lung cancer in people with HIV/AIDS in
the United States. Leonard Chang,
Montclair State University. Mentor: Eric Engels, M.D.,
M.P.H. (VEB)
HHV-8 viral and antibody profiles in patients with Kaposi’s
sarcoma in Uganda. Susan Combs, Oxford
University. Mentor: Sam Mbulaiteye, M.D. (VEB)
Differential gene expression in gastric cardia cancer:
Comparison of two methods. Erica Dawsey,
University of Michigan. Mentors: Philip Taylor, M.D.,
and Nan Hu, M.D., M.P.H. (both in GEB)
Using a geographic information system to evaluate environmental
exposures to solvent releases and risk of non-Hodgkin lymphoma.
Hozefa Divan, University of California, Los
Angeles. Mentor: Mary Ward, Ph.D. (OEEB)
Tobacco use and health behaviors among a cohort of adult
survivors of retinoblastoma. Meredith Foster,
Wellesley College. Mentor: Ruth Kleinerman, M.P.H.
(REB)
Immunophenotypic and clinical protein features of monoclonal
B-cell lymphocytosis in unaffected relatives from B-CLL kindreds.
Shannon Gnall, University of North Carolina
at Chapel Hill. Mentor: Neil Caporaso, M.D.
(GEB)
Changes in serum DDT/DDE levels between 1976 and 1998 among
women from Triana, Alabama in relation to body mass index, parity,
breastfeeding, and other factors. Julia Gray,
University of Michigan. Mentor: Aaron Blair, Ph.D. (OEEB)
Utility of the colored eco-genetic relationship map for
assessing social functioning of women in HBOC families.
Lindsey Hoskins, University of Maryland. Mentor:
June Peters, M.S., C.G.C. (CGB)
Merkel cell carcinoma and multiple primary cancers.
Regan Howard, George Washington University.
Mentor: Lois Travis, M.D., Sc.D. (REB)
Analysis of 1-carbon metabolism in the Spanish Bladder
Cancer study. Sara Karami, George Washington
University. Mentor: Lee Moore, Ph.D. (OEEB)
The NCI dyskeratosis congenita cohort. Sara
Khaghani, University of California, Los Angeles. Mentors:
Blanche Alter, M.D., M.P.H., and Neelam
Giri, M.D. (both in CGB)
Increased non-Hodgkin lymphoma risk in association with
family history of hematopoietic malig- nancies. Zhao
Elizabeth Lan, Churchill High School. Mentor: Sophia
Wang, Ph.D. (HREB)
Association of the CYP17 MspA1 gene polymorphism with prostate
cancer in the ATBC study. Alexis Lebron,
University of Maryland. Mentors: Demetrius Albanes,
M.D., and Margaret Wright, Ph.D. (both
in NEB)
Association of smoking and oral lesions with HHV-8 in
the U.S. population. Luis Lee, Ponce School
of Medicine. Mentor: James Goedert, M.D. (VEB)
Physical activity in relation to all-cause mortality in
the U.S. Radiologic Technologists study. Sharifa
Love-Schnur, Yale University. Mentor: Michal
Freedman, Ph.D. (REB)
MBL2 haplotypes and clearance of hepatitis C among injection
drug users. Rebecca Pass, Stanford University.
Mentors: Thomas O’Brien, M.D., M.P.H.
(HREB), and Beth Brown, Ph.D. (VEB)
Human papillomavirus research from the laboratory to the
clinic to population studies. Jo Pretorius,
University of San Diego. Mentor: Mark Schiffman, M.D.,
M.P.H. (HREB)
Patient and health care provider education materials related
to the management of menopausal symptoms in women who have undergone
risk-reducing salpingo-oophorectomy. Sheila Thomas,
Clemson University. Mentor: Jennifer Loud, M.S.N., C.R.N.P.
(CGB)
Assessing the chance that the finding of a report is false.
Li Zhang, University of Florida. Mentors: Sholom
Wacholder, Ph.D., and Nilanjan Chatterjee,
Ph.D. (both in BB)
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When Mary Lou McMaster,
M.D., Genetic Epidemiology Branch (GEB), wanted to communicate
with participants in her family study of Waldenström macroglobulinemia
(WM), she faced the singular challenge of explaining medical terms
to a mixed audience of knowledgeable patients as well as others who
may know much less about the disease. So she developed a highly effective
newsletter that informs study participants about the disease and fosters
the conduct of the research.
WM
is a rare cancer that arises from B-lymphocytes (a type of white blood
cell) that produce excess amounts of a very large protein called IgM.
Because of its huge size, the excess IgM in the bloodstream makes
the blood viscous, or sticky, leading to such symptoms as visual problems,
nosebleeds, headaches, mental confusion, and rarely, stroke. Based
on data from the NCI Surveillance, Epidemiology, and End Results (SEER)
program, Dr. McMaster estimates that about 1,100 new cases of WM are
diagnosed in the United States annually. Although only 12 WM families
had been described worldwide since 1960, about 80 WM families (including
over 170 WM patients and nearly 450 healthy relatives) have been identified
and enrolled in the DCEG study since it began in 2001.
The DCEG family study of WM is designed to provide insights into
the clinical spectrum of WM when it clusters in families and to identify
genetic factors that contribute to susceptibility. "In general, WM
patients are incredibly well-informed about their disease," said Dr.
McMaster. "When I see a WM patient in the clinic, I am often seeing
someone who knows more about the disorder than most physicians, and
I have the time to explain our study methods and rationale using a
variety of strategies designed to meet individual needs." Dr. McMaster
communicates by letter, telephone, and face-to-face with family members
who come to the NIH Clinical Center, although not all participants
are able to travel to Bethesda for evaluation. "It is much more challenging
to explain scientific and medical concepts about WM and genetic research
methods to healthy relatives of WM patients," she said, "because—unlike
many WM patients—family members may not be aware of, or have
access to, other sources of information."
To meet this need, Dr. McMaster designed a newsletter to be distributed
to all study participants. "I wanted to provide all our family members,
regardless of their level of background knowledge, a working vocabulary
for family and genetic studies in general, and WM in particular. The
newsletter provides me another option to educate our families about
some of the basic scientific concepts behind our work, to address
frequently asked questions, to provide links to other sources of information,
and to continue to express our appreciation for their contribution
to WM research." In addition, each newsletter contains a postage-paid
information form that allows participants to update their individual
or family information, ask questions, and air concerns. Following
the institutional review board approval, approximately 1,000 newsletters
were sent out in May. "The response has been fantastic," said Dr.
McMaster, after receiving more than 380 update forms during the first
eight weeks following the mail-out. "Participant feedback has been
overwhelmingly positive, and we have the added bonus of receiving
some questions and comments that will help guide future issues of
the newsletter."
GENETIC COUNSELING RESEARCH SEMINAR
In June, the Clinical
Genetics Branch co-sponsored a special joint DCEG/Division of
Cancer Control and Population Sciences seminar entitled "Cancer
genetic counseling research: Psychosocial and practice issues"
with presentations by several international speakers. Dr. Elizabeth
Lobb from the University of Sydney spoke on risk communication,
the genetic counseling process, and content analysis; Dr. Nina
Hallowell of the University of Edinburgh presented a synopsis
of her publications on lay understanding of risk, women’s
responses to risk communications, and decision-making regarding
prophylactic surgery for hereditary breast-ovarian cancer.
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Infertility and Cancer
In a retrospective cohort study of 12,193 U.S. women evaluated for
infertility between 1965 and 1988, 581 cases of cancer were identified
through 1999. Infertility patients demonstrated a higher cancer risk
than the general population (standardized incidence ratio [SIR] =
1.23; CI = 1.1–1.3), with nulligravid (primary infertility)
patients at even higher risk (SIR = 1.43; CI = 1.3–1.6). Particularly
elevated risks among primary infertility patients were observed for
cancers of the uterus (SIR = 1.93) and ovaries (SIR = 2.73). Analyses
within the cohort revealed increased rate ratios (RRs) of colon, ovarian,
and thyroid cancers and of melanomas associated with endometriosis.
Melanomas were linked with anovulatory problems, whereas uterine cancers
predominated among patients with tubal disorders. Endometriosis was
linked with distinctive excesses of cancers of the colon (RR = 2.40;
CI = 0.7–8.4), ovaries (RR = 2.88; CI = 1.2–7.1), and
thyroid (RR = 4.65; CI = 0.8–25.6), as well as melanomas (RR
= 2.32; CI = 0.8–6.7). Primary infertility due to anovulation
particularly predisposed to uterine cancer (RR = 2.42; CI = 1.0–5.8).
The effects of infertility may extend beyond gynecologic cancers.
Thyroid cancers and melanomas deserve specific attention, particularly
with respect to endometriosis. (Brinton LA, Westhoff CL, Scoccia
B, Lamb EJ, Althuis MD, Mabie JE, Moghissi KS. Causes of infertility
as predictors of subsequent cancer risk. Epidemiology 2005;16:500–507)
Aspirin Use
The associations of gallbladder and bile duct cancers with gallstones,
cholecystitis, and cholangitis suggest that chronic inflammation contributes
to the carcinogenic process. A population-based case-control study
conducted in Shanghai, China, examined the relationship between aspirin
use and the risk of biliary disease among 627 patients with biliary
tract cancer, 1,037 patients with biliary stones, and 958 healthy
adults. Aspirin use was associated with a reduced risk of gallbladder
cancer (odds ratio [OR] = 0.37; CI = 0.17–0.88), and an inverse
relationship was observed with frequency and duration of use and use
starting at a younger age. In addition, there were non-significant
reductions in the risk of bile duct (OR = 0.48; CI = 0.19–1.19)
and ampullary cancers (OR = 0.22; CI = 0.03–1.65) associated
with aspirin use, whereas no clear association was seen with biliary
stones (OR = 0.92; CI = 0.59–1.44). (Liu E, Sakoda LC,
Gao YT, Rashid A, Shen MC, Wang BS, Deng J, Han TQ, Zhang BH, Fraumeni
JF Jr, Hsing AW. Aspirin use and risk of biliary tract cancer: A population-based
study in Shanghai, China. Cancer Epidemiol Biomarkers Prev
2005;14:1315–1318)
NAT2
and GSTM1 Genes
The authors investigated polymorphisms in NAT2, GSTM1, NAT1, GSTT1,
GSTM3, and GSTP1 in 1,150 patients with transitional-cell
carcinoma of the urinary bladder and 1,149 controls in Spain, and
carried out meta-analyses that included over twice the numbers of
cases in previous reports. The odds ratios for bladder cancer for
individuals with deletion of one or two copies of the GSTM1
gene were 1.2 (CI = 0.8–1.7) and 1.9 (CI = 1.4–2.7), respectively.
Compared with NAT2 rapid or intermediate acetylators, NAT2
slow acetylators had an increased overall risk of bladder cancer (OR
= 1.4; CI = 1.2–1.7) that was stronger for cigarette smokers
than for never smokers (p for interaction = 0.008). No significant
associations were found with the other polymorphisms. Meta-analyses
showed that the overall association for NAT2 was robust (p
< 0.0001), and case-only meta-analyses provided support for
an interaction between NAT2 and smoking (p for interaction
= 0.009). The overall association for GSTM1 was also robust
(p < 0.0001) and was not modified by smoking status (p
= 0.86). The GSTM1 null genotype increases the overall risk
of bladder cancer, and the NAT2 slow-acetylator genotype
also increases risk, particularly among cigarette smokers. Although
the relative risks are modest, these polymorphisms could account for
up to 31% of bladder cancers because of their high prevalence. (García-Closas
M, Malats N, Silverman D, Dosemeci M, Kogevinas M, Hein DW, Tardon
A, Serra C, Carrato A, Garcia-Closas R, Lloreta J, Castaño-Vinyals
G, Yeager M, Welch R, Chanock S, Chatterjee N, Wacholder S, Samanic
C, Tora M, Fernández F, Real FX, Rothman N. NAT2 slow
acetylation, GSTM1 null genotype, and risk of bladder cancer:
Results from the Spanish Bladder Cancer study and meta-analyses. Lancet
2005;366:649–659)
Ataxia-Telangiectasia
Epidemiological studies have consistently shown elevated rates of
breast cancer among female blood relatives of patients with ataxia-telangiectasia
(AT), a rare autosomal recessive disease. A large proportion of the
members of AT families are carriers of AT-causing gene mutations in
ATM, and it has been hypothesized that these otherwise healthy
carriers are predisposed to breast cancer. In a follow-up study of
1,445 blood relatives of 75 patients with verified AT in 66 Nordic
families, 225 cases of cancer were identified through population registries,
with 170.4 expected (SIR = 1.3; CI = 1.1–1.4). Invasive breast
cancer occurred among 34 female relatives (SIR = 1.7; CI = 1.2–2.4)
and was diagnosed among 21 women before the age of 55 years (SIR =
2.9; CI = 1.8–4.5), including seven mothers of probands (SIR
= 8.1; CI = 3.3–17). When the group of mothers was excluded,
no clear relationship was observed between the allocated mutation
carrier probability of each family member and the extent of breast
cancer risk. The findings of breast cancer risk in mothers, but not
other likely mutation carriers, in this and other studies raise questions
about the hypothesis of a simple causal relationship with ATM
heterozygosity. (Olsen JH, Hahnemann JM, Borresen-Dale AL,
Tretli S, Kleinerman R, Sankila R, Hammarstrom L, Robsahm TE, Kaariainen
H, Bregard A, Brondum-Nielsen K, Yuen J, Tucker M. Breast and other
cancers in 1,445 blood relatives of 75 Nordic patients with ataxia
telangiectasia. Br J Cancer 2005;93:260–265)
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Ionizing Radiation and Male Breast
Cancer
Male breast cancers, diagnosed between 1958 and 1998, were
identified among 45,880 male members of the Life Span Study cohort
of Japanese atomic bomb survivors. Nine cases were diagnosed among
exposed cohort members (crude rate = 1.8 per 100,000 person-years),
three were diagnosed among non-exposed cohort members (crude rate
= 0.5 per 100,000 person-years), and a dose-response relation was
observed (excess relative risk per sievert = 8; CI = 0.8–48;
p = 0.01). These findings add to the very limited information
showing an association between radiation exposure and an increased
male breast cancer risk. (Ron E, Ikeda T, Preston DL, Tokuoka
S. Male breast cancer incidence among atomic bomb survivors. J
Natl Cancer Inst 2005;97:603–605)
NIH AWARDS CEREMONY
At the NIH Awards Ceremony held in July, Allan Hildesheim,
Ph.D. (HREB) received the Director’s Award in
recognition of his leadership of the NCI Human Papillomavirus
Vaccine (HPV) Trial 2005. In addition, Linda Morris
Brown, Dr.P.H. (BB), received the Public Health Service
Meritorious Service Award for her leadership and achievements
in the area of cancer-related health disparities research. The
awards were presented by NIH Director Dr. Elias A. Zerhouni.
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Inflammatory Breast Carcinoma
Breast cancer cases diagnosed in the Surveillance, Epidemiology, and
End Results (SEER) Program between 1988 and 2000 were classified as
inflammatory breast carcinoma (IBC) (n = 3,648), non-inflammatory
locally advanced breast cancer (LABC) (n = 3,636), or non-T4
breast cancer (n = 172,940). Between the 1988-1990 and 1997-
1999 time intervals, IBC incidence rates (per 100,000 woman-years)
increased from 2.0 to 2.5 (p < 0.001), whereas those for
LABC declined (2.5 to 2.0; p = 0.0025), as did those for
non-T4 breast cancer (108 to 101; p = 0.0084). IBC incidence
rates were higher among black women (3.1) than among white women (2.2)
(p < 0.001). Median survival of women with IBC (2.9 years)
was shorter than that of women with LABC (6.4 years; p <
0.0001) or non-T4 breast cancer (> 10 years; p < 0.0001).
Black women with IBC or LABC had poorer survival than white women
(p < 0.001). Throughout the 1990s, IBC incidence rose,
and survival improved modestly. Substantial racial differences were
noted in age at diagnosis, age-specific incidence rates, and survival
outcomes. (Hance KW, Anderson WF, Devesa SS, Young HA, Levine
PH. Trends in inflammatory breast carcinoma incidence and survival:
The Surveillance, Epidemiology, and End Results Program at the National
Cancer Institute. J Natl Cancer Inst 2005;97:966–975)
Risk in Women with Oncogenic HPV Types
The two-year absolute risk for cervical precancer attributable to
infection by human papillomavirus type 16 (HPV-16) has not been definitively
evaluated. Within the ALTS (Atypical Squamous Cells of Undetermined
Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study)
population, baseline specimens of 5,060 women with equivocal or mildly
abnormal cytology were tested for HPV DNA. Absolute risks for diagnosis
of cervical intraepithelial neoplasia Grade 3 (CIN3) or cancer during
the two-year study period were calculated by status of HPV-16 and
other oncogenic HPV types. A total of 542 women in the study group
developed CIN3 or cervical cancer. Those who tested positive for HPV-16
had 38 times the risk for CIN3 or cervical cancer of women in the
study who were HPV negative. Women who tested positive for other oncogenic
HPV types had seven times the risk of women who tested HPV-negative.
Thus, patients with a positive HPV-16 diagnosis may require more aggressive
management than those who test positive for another oncogenic HPV
type or who are HPV-negative. (Castle PE, Solomon D, Schiffman
M, Wheeler CM for the ALTS Group. Human papillomavirus type 16 infections
and 2-year absolute risk of cervical precancer in women with equivocal
or mild cytologic abnormalities. J Natl Cancer Inst 2005;97:1066–1071)
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In
an analysis of 20,810 women enrolled in a cohort study based in the
Kaiser Permanente health plan in Portland, Oregon, women who tested
positive for HPV-16 or HPV-18 were diagnosed with CIN3 or cervical
cancer more often than women who tested positive for another oncogenic
HPV type or women who tested negative for HPV. Additional analysis
of women with normal cytology at study enrollment provided further
evidence for the observed risk differences. Screening for HPV-16 and
HPV-18 separately from other oncogenic HPV types may identify women
at greatest risk of developing CIN3 and cervical cancer, while allowing
for less aggressive management of cases of other oncogenic HPV infections
(see Figure 1). (Khan MJ, Castle PE, Lorincz AT, Wacholder
S, Sherman ME, Scott DR, Bush BB, Glass AG, Schiffman M. The elevated
10-year risk of cervical neoplasia in women with human papillomavirus
(HPV) type 16 or 18 and the possible utility of type-specific HPV
testing in clinical practice. J Natl Cancer Inst 2005;97:1072–1079)
Genome-wide Association Study
The authors report application of the Affymetrix, Inc. high-density
single nucleotide polymorphism (SNP) array containing 11,555 SNPs
in a pilot whole-genome association study of germline samples from
50 esophageal squamous cell carcinoma (ESCC) patients and 50 controls.
Thirty-seven SNPs were associated with disease, assuming a recessive
mode of transmission; similarly, 48 SNPs were identified assuming
a dominant mode and 53 SNPs in a continuous mode. When the 37 SNPs
identified from the generalized linear model (GLM) recessive mode
were used in a principal components analysis, the first principal
component correctly predicted 46 of 50 cases and 47 of 50 controls.
Among all SNPs selected from GLMs for the three modes of transmission,
39 could be mapped to 1 of 33 genes. Many of these genes are involved
in various cancers, including GASC1, shown previously to be amplified
in ESCCs, and EPHB1 and PIK3C3. Thus, the feasibility
of the Affymetrix 10K SNP array in genome-wide association studies
of common cancers is shown and new candidate loci for ESCC are identified.
(Hu N, Wang C, Hu Y, Yang HH, Giffen C, Tang ZZ, Han XY, Goldstein
AM, Emmert-Buck MR, Buetow KH, Taylor PR, Lee MP. Genome-wide association
study in esophageal cancer using GeneChip mapping 10K array. Cancer
Res 2005; 65:2542–2546)
Alcohol Intake and Non-Hodgkin Lymphoma
Pooling original data from nine case-control studies from the United
States, the United Kingdom, Sweden, and Italy in the International
Lymphoma Epidemiology Consortium (InterLymph) yielded a study population
of 6,492 non-Hodgkin lymphoma (NHL) cases and 8,683 controls. People
who drank alcohol had a lower risk of NHL than non-drinkers (OR =
0.83; CI = 0.76–0.89). Compared with non-drinkers, risk estimates
were lower for current drinkers (OR = 0.73; CI = 0.64–0.84)
than for former drinkers (OR = 0.95; CI = 0.80–1.14), but risk
did not decrease with increasing consumption. The protective effect
of alcohol did not vary by beverage type but did change with NHL subtype.
The lowest risk estimates were recorded for Burkitt’s lymphoma
(OR = 0.51; CI = 0.33–0.77). Further study is needed to determine
whether confounding lifestyle factors or immunomodulatory effects
of alcohol explain this association. (Morton LM, Zheng T,
Holford TR, Holly EA, Chiu BC, Costantini AS, Stagnaro E, Willett
EV, Dal Maso L, Serraino D, Chang ET, Cozen W, Davis S, Severson RK,
Bernstein L, Mayne ST, Dee FR, Cerhan JR, Hartge P. Alcohol consumption
and risk of non-Hodgkin lymphoma: A pooled analysis. Lancet Oncol
2005;6:469–476)
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Herbicides, Organochlorines, and Non-Hodgkin
Lymphoma
To estimate the effects of residential pesticide exposure on risk
of non-Hodgkin lymphoma (NHL), a population-based case-control study
in Iowa and metropolitan Detroit, Los Angeles, and Seattle was conducted
between 1998 and 2000. Computer-assisted personal interviews (1,321
cases, 1,057 controls) elicited data on pesticide use at each home
occupied since 1970. Herbicide use on the lawn or garden was similar
among cases and controls (adjusted relative risk = 1.02; CI = 0.84–1.23).
Estimated risk did not increase with greater duration, frequency,
or total number of applications of herbicides to the lawn, garden,
or to both combined. Risk was not elevated for respondents who applied
the herbicides themselves or for those exposed during the 1970s, 1980s,
or 1990s. The authors detected 2,4-dichlorophenoxyacetic acid equally
often in dust taken from used vacuum cleaner bags in the current homes
of cases and controls (78%) and dicamba in homes of 15% of cases and
20% of controls. They also found no elevation in risk among the respondents
who had the highest dust levels and highest self-reported exposures.
(Hartge P, Colt JS, Severson RK, Cerhan JR, Cozen W, Camann
D, Zahm SH, Davis S. Residential herbicide use and risk of non-Hodgkin
lymphoma. Cancer Epidemiol Biomarkers Prev 2005;14:934–937)
In another report from the same study, organochlorine concentrations
were measured in vacuum cleaner bag dust from 603 white cases and
443 white controls who had owned most of their carpets for at least
five years. NHL risk was elevated if any of the polychlorinated biphenyl
(PCB) congeners (PCBs 105, 138, 153, 170, or 180) was detected (OR
= 1.5; CI = 1.2–2.0). Risk was elevated in the top tertile of
PCB 180 (OR = 1.7; CI = 1.1–2.6) and in the top two tertiles
of total PCBs (middle tertile, OR = 1.6; CI = 1.1–2.4; top tertile,
OR = 1.5; CI = 1.0–2.2). There was also a positive trend in
risk with increasing PCB 180 levels (p for trend = 0.03).
NHL risk was associated with detection of ichlorodiphenyldichloroethylene
(DDE) (OR = 1.3; CI = 1.0–1.7) only among men, and a positive
dose-response relationship was observed (p for trend = 0.02).
(Colt JS, Severson RK, Lubin J, Rothman N, Camann D, Davis
S, Cerhan JR, Cozen W, Hartge P. Organochlorines in carpet dust and
non-Hodgkin lymphoma. Epidemiology 2005;16:516–525)
Hodgkin Lymphoma Susceptibility Gene
Hodgkin lymphoma (HL) has a strong familial component, but no genes
have been identified. A genome-wide linkage screen was performed in
44 high-risk HL families with a total of 254 individuals providing
DNA samples. Among these families, there were 95 HL cases and four
cases of non-Hodgkin lymphoma (NHL) that were informative for linkage.
Microsatellite markers (n = 1,058) were genotyped with an
average spacing of 3.5 cM, and data were analyzed using both non-parametric
and parametric linkage analysis, with both two-point and multipoint
linkage statistics computed. The strongest linkage finding was on
chromosome 4p near the marker D4S394. The lod score calculated by
Genehunter Plus was 2.6 (nominal p = 0.0002) when both HL
and NHL individuals were considered affected. The mean identity by
descent sharing among 35 affected sibling pairs was 72% in this region
(nominal p = 0.00007). The results are consistent with recessive
inheritance. Other locations suggestive of linkage were found on chromosomes
2 and 11. The number of independent regions identified is more than
expected by chance, although no one region met genome-wide significance
levels. These linkage findings represent the first step towards identifying
one or more loci leading to susceptibility to HL and understanding
its complex etiology. (Goldin LR, McMaster ML, Ter Minassian
M, Saddlemire S, Harmsen B, Lalonde G, Tucker MA. A genome screen
of families at high risk for Hodgkin lymphoma: Evidence for a susceptibility
gene on chromosome 4. J Med Genet 2005;42:595–601)
MC1R and ASIP Genes
Variants of the melanocortin-1 receptor (MC1R) gene and the
Agouti signaling protein (ASIP) gene were examined among
267 melanoma patients and 382 control subjects from a case-control
study and a family study in northeastern Italy in relation to phenotypic
characteristics, sporadic and familial melanoma risk, and melanoma
thickness. MC1R variant alleles were associated with a two- to fourfold
increased risk of sporadic and familial melanoma compared with wild-type
MC1R, particularly among individuals with multiple variant
alleles (OR = 3.9; CI = 3.3–4.6). This association was stronger
among individuals with fewer additional risk factors. MC1R
variant allele carriers were also three to four times more likely
than non-carriers to have thick melanomas. The ASIP polymorphism
was not associated with pigmentation, nevi, or melanoma risk. (Landi
MT, Kanetsky PA, Tsang S, Gold B, Munroe D, Rebbeck T, Swoyer J, Ter
Minassian M, Hedayati M, Grossman L, Goldstein AM, Calista D, Pfeiffer
RM. MC1R, ASIP, and DNA repair in sporadic and familial melanoma in
a Mediterranean population. J Natl Cancer Inst 2005;97:998–1007)
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Supplemented Case-control Design
The supplemented case-control design consists of a case-control sample
and an additional sample of disease-free subjects who arise from a
given stratum of one of the measured exposures in the case-control
study. The supplemental data might, for example, arise from a population
survey conducted independent of the case-control study. This design
improves precision of estimates of main effects and especially of
joint exposures, particularly when joint exposures are uncommon and
the prevalence of one of the exposures is low. The authors first present
a pseudo-likelihood estimator that is easy to compute. They further
adapt two-phase design methods to find maximum likelihood estimates
for the log odds ratios for this design and derive asymptotic variance
estimators that appropriately account for the differences in sampling
schemes of this design from that of the traditional two-phase design.
(Pfeiffer RM, Chatterjee N. On a supplemented case-control
design. Biometrics 2005;61:584–590)
Survivors of Childhood Soft
Tissue Sarcoma
This study evaluated the risk of second cancers among 1,499 children
(age < 18 years) who survived for at least one year after they
were diagnosed with soft tissue sarcoma (STS) and who were reported
to the SEER population-based cancer registries from 1973 to 2000.
Twenty-seven children developed 28 subsequent primary malignancies,
compared with 4.5 expected cancers based on general population rates
(observed-to-expected ratio [O/E] = 6.3; CI = 4.2–9.1). The
risk of developing a subsequent malignancy was increased among children
with rhabdomyosarcoma (11 malignancies; O/E = 7.7), fibromatous neoplasms
(9 malignancies; O/E = 5.8), and other STS (7 malignancies; O/E =
6.5). Initial therapy with radiation and chemotherapeutic agents was
associated with a significantly higher risk compared with surgery
alone (O/E = 15.2 vs.1.4; p < 0.0001). Elevated risks
were observed for acute myeloid leukemia, cutaneous melanoma, female
breast cancer, and sarcomas of the bone and soft tissue, with generally
higher risks among patients who initially received combined modality
therapy. For several children, the pattern of multiple malignancies
was consistent with a genetic syndrome, particularly neurofibromatosis
type 1 and Li-Fraumeni syndrome. (Cohen RJ, Curtis RE, Inskip
PD, Fraumeni JF Jr. The risk of developing second cancers among survivors
of childhood soft tissue sarcoma. Cancer 2005;103:2391–2396)
Thyroid
Cancer after Childhood Cancer
This study aimed to quantify the long-term risk of thyroid
cancer among survivors of malignant disease in childhood who had chemotherapy
or radiotherapy to the head, neck, or upper thorax. In a nested case-control
study, 69 cases with pathologically confirmed thyroid cancer and 265
controls were identified from 14,054 five-year survivors of cancer
from the Childhood Cancer Survivor Study cohort. Risk of thyroid cancer
increased with radiation doses up to 20–29 Gy (OR = 9.8; CI
= 3.2–34.8). At doses greater than 30 Gy, a fall in the dose-response
relation was seen, consistent with a cell-killing effect. Both the
increased and decreased risks were more pronounced among those diagnosed
with a first primary malignant disease before age 10 than among those
older than 10 years (see Figure 2). The fall in risk remained when
those diagnosed with Hodgkin lymphoma were excluded. Chemotherapy
for the first cancer was not associated with thyroid-cancer risk,
and it did not modify the effect of radiotherapy. (Sigurdson
AJ, Ronckers CM, Mertens AC, Stovall M, Smith SA, Liu Y, Berkow RL,
Hammond S, Neglia JP, Meadows AT, Sklar CA, Robison LL, Inskip PD.
Primary thyroid cancer after a first tumour in childhood (the Childhood
Cancer Survivor Study): A nested case-control study. Lancet
2005;365:2014–2023)
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Squamous Cell Carcinomas after Graft-versus-Host
Disease
Previous studies of recipients of hematopoietic stem-cell transplants
suggest that graft-versus-host disease (GvHD) and its therapy may increase
the risk for solid cancers, particularly squamous-cell carcinomas (SCCs)
of the buccal cavity and skin. A case-control study of 183 patients
with post-transplantation solid cancers (58 SCCs, 125 non-SCCs) and
501 matched control patients was conducted within a cohort of 24,011
patients who underwent hematopoietic stem-cell transplantation at 215
centers worldwide. Chronic GvHD and its therapy were strongly related
to the risk for SCC, whereas no increase in risk was found for non-SCCs.
Major risk factors for the development of SCC were long duration of
chronic GvHD therapy, use of azathioprine, particularly when combined
with cyclosporine and steroids, and severe chronic GvHD. The independent
effects of immunosuppressive therapy and azathioprine could not be evaluated.
Prolonged immunosuppressive therapy and azathioprine use were also significant
risk factors for SCC of the skin and of the oral mucosa. Clinical screening
for SCC is appropriate among patients exposed to persistent chronic
GvHD, prolonged immunosuppressive therapy, or both. (Curtis
RE, Metayer C, Rizzo JD, Socie G, Sobocinski KA, Flowers ME, Travis
WD, Travis LB, Horowitz MM, Deeg HJ. Impact of chronic GVHD therapy
on the development of squamous-cell cancers after hematopoietic stem-cell
transplantation: An international case-control study. Blood
2005;105:3802–3811)
Risk of Contralateral Testicular
Cancer
Although risk estimates for synchronous and metachronous contralateral
testicular cancers vary widely, many clinicians recommend routine biopsy
of the contralateral testis for patients with unilateral testicular
cancer. Among 29,515 testicular cancer cases diagnosed before age 55
and reported to the NCI SEER Program from 1973 to 2001, 175 men presented
with synchronous contralateral testicular cancer, and 287 men developed
metachronous contralateral testicular cancer (O/E = 12.4; CI = 11.0–13.9).
The
15-year cumulative risk was 1.9% (CI = 1.7%–2.1%). In multivariable
analyses, non-seminomatous histology of the first testicular cancer
was associated with a decreased risk of metachronous contralateral testicular
cancer (hazard ratio [HR] = 0.60; CI = 0.46–0.79; p <
0.001) (see Figure 3). Increasing age at first testicular cancer diagnosis
was associated with decreasing risk of non-seminomatous metachronous
contralateral testicular cancer (OR = 0.90; CI = 0.86–0.94).The
10-year survival rate after metachronous contralateral cancer diagnosis
was 93% (CI = 88%–96%), and that after synchronous contralateral
cancer was 85% (CI = 78%–90%). The low cumulative risk of metachronous
contralateral cancer and favorable overall survival of patients diagnosed
with metachronous contralateral testicular cancer is consistent with
the current U.S. approach of not performing a biopsy on the contralateral
testis. (Fossa SD, Chen J, Schonfeld SJ, McGlynn KA, McMaster
ML, Gail MH, Travis LB. Risk of contralateral testicular cancer: A population-based
study of 29,515 U.S. men. J Natl Cancer Inst 2005;97:1056–1066).
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Michael C. R. Alavanja, Dr.P.H., Occupational and
Environmental Epidemiology Branch (OEEB), and Matthew Bonner,
Ph.D. (OEEB), co-chaired an Agricultural Health Study Biomarker
Workshop in March in Research Triangle Park, North Carolina. The proceedings
were published in the Journal of Biochemical and Molecular Toxicology
(Volume 19, Number 3, 2005).
Blanche Alter, M.D., M.P.H., Clinical Genetics Branch
(CGB), gave a lecture on “Cancer-prone rare genetic syndromes:
How do they instruct us?” at the Genome Damage and Stability
Centre, University of Sussex in Brighton, England in June. Later in
the month, Dr. Alter spoke on “MDS/AML in patients with Shwachman-Diamond
Syndrome receiving long-term G-CSF” at the Third International
Congress on Shwachman-Diamond Syndrome in Robinson College, Cambridge,
England.
Gabriella
Andreotti, M.P.H., Hormonal and Reproductive Epidemiology
Branch (HREB), had an abstract entitled “Polymorphism of
genes in the lipid metabolism pathway and the risk of biliary
tract cancers: A population-based study in Shanghai, China”
accepted for the Second Annual NIH Graduate Student Research Symposium,
which was held in April. |
Robert
Biggar, M.D., Viral Epidemiology Branch (VEB), gave a
presentation on “Mother-child HLA concordance as a risk
factor for HTLV-I transmission” at the 12th International
Conference on Human Retrovirology: HTLV and Related Viruses in
Montego Bay, Jamaica in June. |
Aaron
Blair, Ph.D. (OEEB), gave an invited
talk on “The interaction of science and ethics on issues
in occupational health” at the International Conference
in Memory of Olav Axelson in Borgholm, Sweden in May. Later in
June, Dr. Blair and Michael Hauptmann, Ph.D.,
Biostatistics Branch (BB), organized a meeting of a working group
at the NCI in Rockville to discuss updating their study of a cohort
of industrial workers exposed to formaldehyde. The working group
consisted of Dr. Elisabeth Fontham (Louisiana State University),
Dr. Michael Thun (American Cancer Society), and Dr. Noah Seixas
(University of Washington); the meeting was attended by representatives
from industry, unions, the U.S. Environmental Protection Agency
(EPA), and advocacy groups. |
Philip
Castle, Ph.D. (HREB), spoke on “Natural history
of HPV infection and the role of the cervical microenvironment”
at Brigham and Women’s Hospital, Harvard University in May.
He then gave talks on “New strategies for cervical cancer
prevention” for the Community Networks Cancer Health Disparities
Summit 2005 in Rockville, Maryland in July, and on “HPV
DNA testing in cervical cancer screening” at the Centers
for Disease Control and Prevention in Atlanta in August. Dr. Castle
also chaired a panel discussion on “Clinical utility of
genomic HPV testing” at the 22nd International Papillomavirus
Conference in Vancouver, British Columbia, Canada in May. |
Shih-Chen
Chang, Ph.D., Nutritional Epidemiology Branch (NEB),
and Hong Hong Zhu, M.D., M.H.S., M.Sc. (OEEB),
have been appointed to represent DCEG on the NIH Fellows Committee,
also known as FELCOM. They are replacing Beth Brown,
Ph.D. (VEB), and Mathew Bonner, Ph.D.
(OEE).
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Nilanjan Chatterjee, Ph.D. (BB), addressed
a symposium in applied and computational mathematics at the
New Jersey Institute of Technology in Newark in May. The title
of his talk was “Semiparametric maximum-likelihood estimation
exploiting gene-environment independence in case-control studies.”
He also gave a talk entitled “Exploiting gene-environment
independence in family-based case-control studies: Increased
power for detecting associations, interactions, and joint effects”
at the International Chinese Statistical Association’s
Applied Statistical Symposium in Bethesda, Maryland in June.
Mustafa Dosemeci, Ph.D. (OEEB), and Patricia
Stewart, Ph.D. (OEEB), spoke on “Exposure estimation
in occupational epidemiology studies” at a National Academies
of Sciences meeting held in Irvine, California in June.
Eric Engels, M.D., M.P.H. (VEB), gave an invited
talk on “Chronic immune stimulation and non-Hodgkin lymphoma”
at the University of Southern California in Los Angeles in April.
He also gave a talk on “Lung cancer in people with HIV
infection” at the University of Texas M.D. Anderson Cancer
Center in Houston in June.
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Mary
Lou McMaster, M.D. (GEB), received the Surgeon General’s
Exemplary Service Award for her work as director of the Public
Health Service Choral Ensemble for the past four years. |
Mitchell
Gail, M.D., Ph.D. (Chief of BB), spoke on the topic “On
criteria for evaluating models of absolute risk” at the
University of Rochester in April. He also gave an invited talk
entitled “Using case-control and case-only probands with
family history to estimate genotype-specific cumulative risk”
at the American Statistical Association meeting in Minneapolis
in August. |
Ethel
Gilbert, Ph.D., Radiation Epidemiology Branch (REB),
gave two invited talks: “Recent epidemiologic data contributing
to cancer risk assessment” at the annual Society of Nuclear
Medicine meeting in Toronto in June and “The Biological
Effects of Ionizing Radiation (BEIR VII) report’s models
for estimating cancer risks” at the annual Health Physics
Society meeting in Spokane, Washington in July. |
James Goedert, M.D. (Chief of VEB), gave a
lecture entitled “Breast cancer: Is there a human virus?”
at the University of Palermo in Italy in July.
Mark Greene, M.D. (Chief of CGB), gave a talk
on “New cancer genes and syndromes” at a conference
on Cancer Control through Genetics at the University of Chicago
Center for Clinical Cancer Genetics in June.
Patricia Hartge, Sc.D., Epidemiology and
Biostatistics Program (EBP), chaired the Family History session
and spoke on “Summary of progress and future direction”
at the annual International Lymphoma Epidemiology Consortium
(InterLymph) meeting in York, England in July.
Marianne Henderson, M.S., Chief of the Office
of Division Operations and Analysis (ODOA), co-led a workshop
on “Designing and developing a repository database”
at the annual International Society for Biological and Environmental
Repositories meeting in Seattle in May. Her presentation focused
on the data management considerations and challenges faced by
large biorepositories.
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Michie
Hisada, M.D., Sc.D. (VEB), chaired the Epidemiology Workshop
at the 12th International Conference on Retrovirology: HTLV and
Related Viruses in Montego Bay, Jamaica in June. |
Ann Hsing, Ph.D. (HREB), gave a presentation
on “Reproducibility data on GC-MS and RIA serum and tissue
assays” at the Endogenous Hormones and Prostate Cancer
Collaborative Group meeting held at Oriel College in Oxford,
England in June. She also gave a talk on the epidemiology of
prostate and biliary tract cancers at the Cancer Research United
Kingdom Epidemiology Unit, University of Oxford. In addition,
Dr. Hsing became a member of the Editorial Board of Cancer
Epidemiology, Biomarkers & Prevention in August.
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Jose
Jeronimo, M.D. (HREB), gave a talk on “Colposcopic
evaluation of HPV positive patients” at the 12th World Congress
of Cervical Pathology and Colposcopy, organized by the International
Federation of Cervical Pathology and Colposcopy, in Cancun, Mexico
in June. He spoke on “A new approach to HPV testing and
cervical cancer screening” at the July NCI Community Networks
Cancer Health Disparities Summit. |
Daehee Kang, M.D., Ph.D. (OEEB), gave an invited
talk on “The gene-environment interactions of breast cancer”
at the Columbia University School of Public Health in June.
Ruth Kleinerman, M.P.H. (REB), presented a
talk on “Risk of new cancers following radiotherapy in
long-term survivors of retinoblastoma” at the International
Society of Genetic Eye Diseases and International Retinoblastoma
Symposium in Whistler, British Columbia, Canada in September.
Ola Landgren, M.D., Ph.D., Genetic Epidemiology
Branch (GEB), gave a talk entitled “Outcome is improving
in chronic lymphocytic leukemia: A population-based study on
9,756 patients diagnosed in Sweden 1973–2001” at
the 10th Congress of the European Hematology Association in
Stockholm in June.
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Hong-Chuan
Li, Ph.D. (VEB), gave a presentation on “Serologic
and molecular characteristics of atypical HTLV Western blot banding
patterns in Jamaican blood donors” at the 12th International
Conference on Human Retrovirology: HTLV and Related Viruses in
Montego Bay, Jamaica in June. |
Martha Linet, M.D., M.P.H. (Chief of REB),
presented a talk on “Radiation spectrums and mechanisms:
An overview of the role of radiation in the etiology of childhood
leukemia” at the Childhood Leukemia Workshop at the Institute
of Child Health in London in April. She also gave a talk on “Epidemiological
and dosimetry needs after radiation disasters: Lessons from six
decades of studies” to the Radiation Nuclear Federal Interagency
Working Group at the National Institute of Allergy and Infectious
Diseases in Bethesda, Maryland in May. |
Lee
Moore, Ph.D. (OEEB), gave an invited talk on “Molecular
epidemiological studies of cancer risk in human populations exposed
to arsenic in drinking water” at the Penn State College
of Medicine in Hershey in May. |
Lindsay Morton, Ph.D. (HREB), spoke on “Proposed
nested classification of lymphoma subtypes for use in epidemiologic
studies” at the July InterLymph meeting in York, England.
Jay Nuckols, Ph.D. (OEEB), organized and chaired
a session on “Exposure considerations for emerging chemical
by-products due to alternative water disinfection practices”
at the EPA’s Optimizing the Design and Interpretation
of Epidemiologic Studies to Consider Alternative Disinfectants
of Drinking Water Workshop in Raleigh, North Carolina in June.
June Peters, M.S., C.G.C. (CGB), served on
the Scientific Advisory Committee and as an abstract reviewer,
session moderator, and presenter at the Ninth International
Psychosocial Aspects of Hereditary Cancer meeting in Philadelphia
in June. She also spoke on “Family systems and genetic
counseling” for the clinical supervisors of the Genetic
Counseling Training Program at Sarah Lawrence College in Bronxville,
New York in July.
Charles Rabkin, M.D. (VEB), gave invited talks
on “Molecular epidemiology of AIDS-related lymphoma”
at Alfried Krupp College and at the Ernst Moritz Arndt University
in Greifswald, Germany in July.
Elaine Ron, Ph.D. (REB), gave talks on “Thyroid
cancer patterns in countries belonging to the Middle East Cancer
Consortium (MECC)” and “Brain and other CNS cancer
patterns in countries belonging to the MECC” in Lyon,
France in June. Later that month, she also spoke about the U.S.
Radiologic Technologists Health Study at the Health Protection
Agency in Chilton, England.
Arthur Schatzkin, M.D., Dr.P.H. (Chief of
NEB), delivered a lecture entitled “Promises and perils
of validating biomarkers for cancer risk” at a Joint U.S.
Food and Drug Administration (FDA)–NCI–Office of
Dietary Supplements Workshop on Use and Misuse of Biomarkers
as Indicators of Cancer Risk Reduction Following Dietary Manipulation
in Bethesda, Maryland in July.
Rashmi Sinha, Ph.D. (Deputy Chief of NEB),
gave a talk on “Meat-derived carcinogens and cancer”
at the FDA National Center for Toxicological Research in Jefferson,
Arkansas in May. In September, Dr. Sinha and Michael
Leitzmann, M.D., Dr.P.H. (NEB), presented talks on
“Diet and cancer epidemiologic studies in developing countries”
and “Dietary measurement error: What next?” as well
as “Assessment and validation of physical activity in
epidemiologic studies” and “Physical activity in
epidemiologic studies,” respectively, at the Asia Cohort
Consortium meeting in Seoul, South Korea. A few days later,
Dr. Sinha also gave a talk on “The options in dietary
assessment method for large cohort studies” at the School
of Public Health at Seoul National University.
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Philip
Taylor, M.D., Sc.D. (GEB), spoke on “Genome-wide
association study in esophageal cancer using GeneChip 10K array”
at the Digestive Diseases Week in Chicago in May. In addition,
Dr. Taylor gave a talk on “Genetics in the etiology, early
detection, and prevention of upper gastrointestinal cancers”
at the Cancer Institute, Chinese Academy of Medical Sciences in
Beijing in June. |
Lois B. Travis, M.D., Sc.D. (REB), chaired
a session on “Cancer survivorship: Long-term effects of
treatment” at the annual American Society of Clinical
Oncology (ASCO) meeting in June. She has also been appointed
to the National ASCO Cancer Survivorship Task Force.
Margaret A. Tucker, M.D. (Chief of GEB), gave
talks on “Prevention and detection of early stage melanoma,”
“Dissecting risk modifiers in inherited cancer syndromes,”
and “Melanoma genetics: Where are we?” at the ASCO
meeting in Orlando in May. She also chaired an educational session
entitled “Update on inherited cancer syndromes: Beyond
breast, ovarian, and colon cancers” at the same meeting.
Sholom Wacholder, Ph.D. (BB), participated
in an invited session on “Bayesian methods in cancer research”
at the American Statistical Association meeting in Minneapolis
in May. He gave another invited lecture, “What is the
chance of an incorrect conclusion about a test of association
between a genetic variant and risk of cancer?” at a Memorial
Symposium for Baruch Modan at Chaim Sheba Hospital in Tel Hashomer,
Israel in the same month. He also addressed the Annual Israeli
Statistical Association meeting in Tel Aviv on “What is
the chance that a negative report is a false negative?”
Sophia Wang, Ph.D. (HREB), spoke on “The
role for identifying common genetic polymorphisms in cancers
with unknown and known etiologies: Non-Hodgkin lymphoma and
cervical neoplasia” at the University of British Columbia
and British Columbia Cancer Research Centre in Vancouver, Canada
in May. Also in that month, Dr. Wang was an invited speaker
on “Methylation events in cervical cancer: Identification
in tissue and validation in cytology specimens” at the
Johns Hopkins School of Medicine. In addition, she gave a talk
on “Family history of hematopoietic malignancies and risk
for non-Hodgkin lymphoma” at the InterLymph meeting in
York, England in July.
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Rashmi
Sinha, Ph.D. has recently been appointed Deputy Branch
Chief of the Nutritional Epidemiology Branch (NEB). In this new
position, her responsibilities include developing a program for
career development for junior investigators within the Branch.
In particular, she will coordinate the recruitment, training,
and professional development of tenure-track investigators and
pre- and postdoctoral fellows. Dr. Sinha will also promote collaborative
activities within ongoing Division studies.
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Elyse Wiszneauckas, a Scientific Program Specialist
(ODOA), received a B.S. degree in Information Systems Management
from the University of Maryland University College in August.
Hong Hong Zhu, M.D. (OEEB), gave a presentation
on “Secondhand tobacco smoke and breast cancer: A nested
case-control study in the Shanghai Women’s Health Study”
at the CCR Combined Faculty Retreat in Cumberland, Maryland
in July, which was sponsored by the Breast and Gynecologic Malignancies
Faculty, the Cancer Prevention Faculty, and the Mouse Models
for Mammary Cancer Collective.
Several DCEG researchers recently received funding support
from the NIH Office of Rare Diseases. Aaron Blair, Ph.D.
(OEEB), will develop an International Consortium for
Studies of Cancer and Other Diseases in Agricultural Populations.
Allan Hildesheim, Ph.D. (HREB), Ann
Hsing, Ph.D. (HREB), and Charles Rabkin, Ph.D.
(VEB), will hold a workshop on Chronic Inflammation and Cancer:
Biology, Pathology, Immunology, and Epidemiology. Elaine
Ron, Ph.D. (REB), will conduct a research project on
the ALARA Concept in Pediatric Interventional and Fluoroscopic
Imaging.
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Mohamad
Al-Rahawan, M.D., a pediatric hematology/oncology fellow
at Children’s National Medical Center and George Washington
University Medical Center in Washington, DC, has joined the Clinical
Genetics Branch (CGB) as a special volunteer. He will be performing
the research component of his training program. Dr. Al-Rahawan
began his pediatric hematology/oncology training at the University
of Virginia in Charlottesville before moving to Washington, DC.
He will be working with Blanche Alter, M.D., M.P.H.,
and Neelam Giri, M.D., on the Inherited Bone
Marrow Failure Syndromes protocol. |
William Anderson, M.D., M.P.H., has joined the
Biostatistics Branch (BB) as a tenure-track investigator. Dr.
Anderson is board-certified in internal medicine, hematology,
and medical oncology. He earned an M.P.H. in epidemiology before
joining the Division of Cancer Prevention (DCP) in 2000. In DCP,
he began a series of studies into the descriptive epidemiology
of cancer, some in collaboration with staff members from DCEG.
Dr. Anderson will develop a research program on descriptive epidemiology,
focusing on its connections to clinical findings and analytical
epidemiology, particularly for breast cancer. |
Stefan
Boehringer, M.D., has joined BB as a special volunteer
and will be working on gene association studies with Ruth
Pfeiffer, Ph.D. He received a degree in medicine from
the University of Bochum, Germany, with further training and experience
at Essen University, where he worked in the Department of Human
Genetics. He is currently completing a Ph.D. dissertation in statistics
at the University of Dortmund. |
Matthew Bonner, Ph.D., a postdoctoral fellow in
the Occupational and Environmental Epidemiology Branch (OEEB) since
2003, has accepted a faculty position at the State University of New
York at Buffalo. While at DCEG, he worked on the Agricultural Health
Study, investigating associations between pesticide exposures and
cancer. He also worked on the role of radon exposure, exposure to
smoky coal, and genetic polymorphisms in the etiology of lung cancer.
Gabriel
Chodick, Ph.D., has joined the Radiation Epidemiology
Branch (REB) as a postdoctoral fellow. Dr. Chodick was an epidemiologist
in Maccabi Health Care Services, the second largest health maintenance
organization in Israel. He received a Ph.D. in epidemiology and
preventive medicine from the Tel Aviv University Medical School
in 2003. Dr. Chodick will work on an extended follow-up of a cohort
of more than 35,000 hyperthyroid patients treated with radioiodine,
surgery, or drugs. |
Robert
N. Hoover, Sc.D., M.D., Epidemiology and Biostatistics
Program (EBP), was awarded the 22nd Abraham Lilienfeld Award for
lifetime contributions to epidemiology. His career is marked by
30 years at the NCI. He has held positions of ever increasing
responsibility within the research infrastructure, from staff
associate to Director of EBP, and his resume contains nearly 400
publications. This outstanding career was recognized by the American
College of Epidemiology in September.
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Ben Hulley, a predoctoral CRTA fellow in the Genetic
Epidemiology Branch (GEB), was recently accepted into the School of
Medicine at the University of California, San Diego. During his time
in GEB, he worked with Mary Lou McMaster, M.D., on
long-term outcomes associated with familial Waldenström’s
macroglobulinemia. He also worked with Maria Teresa Landi,
M.D., Ph.D., on the role of genes involved in regulation
of the immune system and of pigmentation in the development and progression
of malignant melanoma.
Michelle Khan, M.P.H., recently finished a two-year
program as a Howard Hughes Medical Institute (HHMI)-NIH Research Scholar,
working with Mark Schiffman, M.D., M.P.H. (HREB),
and returned to the University of Medicine and Dentistry of New Jersey-Robert
Wood Johnson Medical School as a third year medical student. While
with HREB, she authored seven papers, including two in the Journal
of the National Cancer Institute. In recognition of her remarkable
progress at NIH, Ms. Khan won a Continuing Support for Completion
of Medical Studies Research Training fellowship from HHMI, a fully
funded award for the current year in medical school.
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Sheng
Luo, Ph.D., joined BB in August as a visiting fellow.
Dr. Luo has master’s degrees in statistics and engineering
and a Ph.D. in applied mathematics. He is now a Ph.D. candidate
in biostatistics at Johns Hopkins Bloomberg School of Public Health.
Dr. Luo will be working on his dissertation project with Nilanjan
Chatterjee, Ph.D. |
Rajeev
Mahajan, M.S., has joined OEEB as a predoctoral fellow.
He received an M.S. in epidemiology from Johns Hopkins Bloomberg
School of Public Health. Mr. Mahajan will investigate associations
between pesticide exposures and cancers. He will also be developing
a biomarker protocol to investigate the carcinogenic mechanisms
of certain pesticides. |
Alyssa Voss Minutillo, M.P.H., has returned to
the DCEG Office of the Director as a technical writer/editor.
Ms. Minutillo, who has an undergraduate degree in biology from
Simmons College, first joined the Division as a health communications
fellow in 2002 while completing her M.P.H. degree from the University
of South Florida. Upon finishing her NCI fellowship, she worked
as a Research Associate at the George Washington University Biostatistics
Center, coordinating multi-center clinical trials for the National
Institute of Diabetes and Digestive and Kidney Diseases on the
prevention and treatment of pediatric type 2 diabetes. |
Beata Peplonska, M.D., Ph.D., has returned to the
Nofer Institute of Occupational Medicine in Lodz, Poland after spending
a year sabbatical in OEEB. She was a field manager for the Lodz component
of the collaborative Breast Cancer Study in Poland. During her year
in DCEG, she analyzed data on occupational exposures and physical
activity in the development of breast cancer.
Tanuja Rastogi, Sc.D., a postdoctoral fellow in
the Nutritional Epidemiology Branch (NEB), became a science policy
fellow with the U.S. State Department in Washington, DC, in September
as part of an American Association for the Advancement of Science
fellowship program. Dr. Rastogi joined NEB in 2002 and worked on a
pilot study for a cohort in India as well as study of cancer incidence
rates among Asian Indians residing in several countries, including
the United States.
Melissa
Rotunno, Ph.D., has joined GEB as a postdoctoral fellow.
She has a B.S. and a Ph.D. in physics from the University of Milan.
Dr. Rotunno will be working with Maria Teresa Landi, M.D.,
Ph.D., and Neil Caporaso, M.D., on the
analyses of complex genomic and epidemiologic data from a case-control
study of lung cancer. |
Sheri Dixon Schully, Ph.D., a Presidential Management
Fellow, has joined the Office of Division Operations and Analysis
(ODOA) for a three-month internship. Dr. Schully received a Ph.D.
in biological sciences from Louisiana State University in 2005.
Her doctoral work focused on evolutionary genetics using Drosophila
as a model system. She will be developing a communication plan
for the Cancer Genetics Markers of Susceptibility (CGEMS) project
with Marianne Henderson, M.S. |
Shunro Sonoda, M.D., Ph.D., has joined the Viral
Epidemiology Branch (VEB) as a visiting scientist. His expertise
is in virology and immunology, with particular emphasis on human
T-lymphotropic virus type I (HTLV-I) and the human leukocyte antigen
system. At the Kagoshima University Faculty of Medicine in Japan,
he was professor and chair of the Department of Virology from
1990 to 2001 and professor and chair of the Department of Island
Medicine from 2001 to 2003. At VEB, Dr. Sonoda will help with
studies of HTLV-I infection and the related diseases, adult T-cell
leukemia and HTLV-1–associated myelopathy/tropical spastic
paraparesis, in Jamaica, where HTLV-1 is endemic. |
Isabelle Thierry-Chef, Ph.D., a visiting fellow
in REB, is joining the International Agency for Research on Cancer,
where she will be studying the effects of plutonium on the risk of
lung cancer. During her year at REB, Dr. Thierry-Chef assessed doses
of ionizing radiation due to medical exposures in a study of pediatric
patients undergoing interventional radiology procedures and a study
of breast doses from different types of diagnostic examination.
Anne
C.M. Thiébaut, Ph.D., has joined NEB as a visiting
fellow. She received her doctoral degree at the National School
of Statistics and Information Analysis in France and an M.P.H.
in epidemiology at the University of Paris XI. She will evaluate
the association between breast cancer risk and dietary fatty acid
intake in the American Association of Retired Persons (AARP) cohort
study. She also plans to investigate the impact of measurement
error on dietary associations with cancer. |
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Jocelyn
Weiss, Ph.D., has joined OEEB as a postdoctoral fellow.
She has a B.S. in biology and child development and an M.P.H.
in epidemiology and biostatistics, both from Tufts University.
She recently obtained a Ph.D. in epidemiology from the University
of Washington in Seattle. For her dissertation, she studied polymorphisms
in nucleotide excision repair genes and risk of endometrial cancer.
Dr. Weiss will be working with Richard Hayes, D.D.S.,
Ph.D., on the investigations of cancer risk in the Prostate,
Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. |
Kelly Yu, M.P.H., has joined HREB as a predoctoral
fellow. She is currently a student in the Department of Epidemiology
at Johns Hopkins Bloomberg School of Public Health. Ms. Yu received
an M.P.H. in chronic disease epidemiology from Yale University in
2000. She will be working on a follow-up study of high-risk individuals
from a cohort of multiplex families with nasopharyngeal cancer in
Taiwan with Allan Hildesheim, Ph.D.
Mingdong Zhang, M.D., Ph.D., a research fellow
in VEB, has accepted a position as an assistant professor at the Center
for Emerging Infectious Disease, Chinese University of Hong Kong.
Yawei Zhang, M.D., Ph.D., an HREB postdoctoral fellow,
recently began work as an assistant professor in the Department of
Epidemiology and Public Health at the Yale University School of Medicine.
While with HREB, she focused on early-life exposure to maternal hormones
in relation to testicular cancer risk, on DNA repair genes in relation
to breast cancer risk, and on genetic susceptibility to non-Hodgkin
lymphoma.
DCEG PARTICIPATES IN SOCIETY FOR EPIDEMIOLOGIC
RESEARCH MEETING
DCEG researchers participated
in the Joint Meeting of the Society for Epidemiologic Research
(SER) and the Canadian Society for Epidemiology and Biostatistics
in Toronto in June by presenting posters and moderating educational
sessions on their work. As president of SER, Maureen
Hatch, Ph.D., Radiation Epidemiology Branch (REB),
delivered the presidential address on “Epidemiology without
borders,” which was the theme of the meeting. She called
for epidemiologists to extend their professional activities
beyond national or disciplinary borders, not only to achieve
an important scientific or public health result, but also to
stimulate new ideas and develop new partnerships. “The
present and future of epidemiology lie in transdisciplinary
team science,” she said. “The new challenge is partnership
with quite different disciplines.”
The annual three-day event also featured a keynote address
by Dr. George Davey-Smith, University of Bristol, and workshops,
symposia, roundtables, poster sessions, and special exhibits
by various epidemiologic programs.
In addition to Dr. Hatch, other DCEG staff also played leadership
roles in the meeting. Louise Brinton, Ph.D.
(HREB), gave a presentation at a spotlight session and also
led a roundtable on “Unresolved issues regarding exogenous
hormones and cancer risk.” Patricia Hartge, Sc.D.
(EBP), presented a poster on “Reporting participation
in epidemiologic studies: A survey of practice” and ran
a symposium entitled “The changing face of epidemiology”
with Dr. David Hunter, Harvard University, and Dr. John Potter,
Fred Hutchinson Cancer Research Center, at which she also spoke.
Rachael Stolzenberg-Solomon, Ph.D. (NEB),
delivered a talk which was also selected for oral presentation
in a spotlight session on cancer called “Pathways to cancer:
Lifestyle, obesity, and metabolism.” Sholom Wacholder,
Ph.D. (BB), organized a symposium entitled “When
should a finding be considered positive? Alternatives to p-value
< 0.05, 95% confidence intervals, and Bonferroni correction,”
at which he also spoke.
DCEG PRESENTERS
Kenneth Adams, Ph.D. (NEB): Association between
body mass and colon cancer
Matthew Bonner, Ph.D. (OEEB): Malathion exposure
and cancer incidence in the Agricultural Health Study
Louise Brinton, Ph.D. (HREB): Relationship
of benign gynecologic diseases to subsequent risk of ovarian
and uterine cancers
Jinbo Chen, Ph.D. (BB): Quantifying selection
bias in epidemiologic studies
Patricia Hartge, Sc.D. (EBP): Declining participation:
How bad is it? What is the solution?
Unhee Lim, Ph.D. (NEB): Anthropometric indicators
and risk of lymphoid malignancies in the prospective NIH-AARP
diet and health study
Katherine McGlynn, Ph.D. (HREB): Relationship
between cryptorchism and maternal hormone levels
Mark Purdue, Ph.D. (OEEB):
Hormone replacement therapy and colorectal adenomas: Data from
the PLCO Cancer Screening Trial
Cecile Ronckers, Ph.D. (REB): Radiation and
thyroid cancer in the Childhood Cancer Survivor study: A detailed
evaluation of dose-response and its modifiers
Rachael Stolzenberg-Solomon, Ph.D. (NEB): Insulin,
glucose, insulin resistance, and pancreatic cancer in male smokers
Margaret Wright, Ph.D. (NEB): Serum vitamin
E in relation to total and cause-specific mortality in the Alpha-tocopherol,
Beta-carotene study
Sholom Wacholder, Ph.D. (BB): When should a
finding be considered positive? Alternatives to
p-value < 0.05, 95% confidence intervals, and Bonferroni
correction
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Dr.
Michael Thun, Vice President of Epidemiology and Surveillance Research
at the American Cancer Society (ACS), spent two days in May at DCEG
as a Visiting Scholar. Dr. Thun, who leads the ACS Cancer Prevention
Study-II Nutrition Cohort, has had a distinguished career in cancer
epidemiology and public health focused on the role of tobacco, pharmaceutical
agents, nutrition, occupational exposures, and genetic susceptibility
in the causation of human cancer. Dr. Thun was one of the first investigators
to demonstrate a reduced risk of colon cancer among regular aspirin
users, thereby prompting a surge of interest in the relation between
inflammation and carcinogenesis. His work on tobacco has included contributions
to consensus reports of the U.S. Surgeon General and the International
Agency for Research on Cancer. He currently holds adjunct professorships
at the Rollins School of Public Health and Winship Cancer Institute
of Emory University.
In his keynote address, Dr. Thun presented a thought-provoking seminar
entitled “Absolute risks: What does the orphan of epidemiology
have to teach us?” in which he outlined the relevance of absolute
risk estimates to average and individual risks (e.g., Gail and Harvard
risk models). He also discussed risk-benefit evaluations, the development
and delivery decision-making process, and epidemiologic applications.
Expanding on this topic, he related absolute individual risk estimates
to absolute population burden, using attributable mortality from obesity
as a case study (see Figure 1). Dr. Thun highlighted the wide range
in estimated U.S. deaths attributable to obesity in recent publications
and related it to choice of referent group (and the problem of reverse
causation), uncontrolled confounding, small population size with limited
statistical power, and some random error. In conclusion, Dr. Thun
emphasized that accurate relative risk estimates are vital to the
development of reliable population attributable risk estimates.
Following
the talk, Joseph F. Fraumeni, Jr., M.D., DCEG Director,
presented Dr. Thun with a plaque in recognition of his distinguished
contributions to cancer epidemiology and his service as a member of
the NCI Board of Scientific Counselors.
Over the course of the two-day visit, Dr. Thun met with various groups
and held a lunch-time discussion of career issues with DCEG fellows.
In a series of meetings, he provided advice on current DCEG research
efforts, including sessions on tobacco, molecular epidemiology, and
lung cancer led by Neil Caporaso, M.D. (Genetic Epidemiology
Branch [GEB]), Maria Teresa Landi, M.D., Ph.D. (GEB),
and Andrew Bergen, Ph.D. (GEB); the role of inflammation
and NSAIDs led by Sophia Wang, Ph.D. (Hormonal and
Reproductive Epidemiology Branch [HREB]), and Eric Engels,
M.D., M.P.H. (Viral Epidemiology Branch); and a variety of
other topics, including the NCI Cancer Genetic Markers of Susceptibility
(CGEMS) project with Dr. Fraumeni, Stephen Chanock, M.D.
(Core Genotyping Facility), and Robert Hoover, M.D., Sc.D.
(Epidemiology and Biostatistics Program), and the ongoing NCI-ACS
collaborative study involving Ann Hsing, Ph.D. (HREB).
The visit culminated with a timely session dedicated to obesity and
cancer led by Michael Leitzmann, M.D., Dr.P.H. (Nutritional
Epidemiology Branch [NEB]), and Arthur Schatzkin, M.D., Dr.P.H.
(NEB), followed by a review of the NCI Energy Balance Initiative by
Dr. Rachel Ballard-Barbash of NCI’s DCCPS and a presentation
by Barry Graubard, Ph.D., of the Biostatistics Branch,
on the impact of obesity on total mortality in the United States.
—Demetrius Albanes, M.D.
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