|
 “We
pride ourselves on doing this,” says Dr. Hoover, “and we’re good at it,
having done it for many years.” It also helps that the Division is in
the position to know about and have access to national resources like
the Social Security Administration, the National Center for Health Statistics,
the Department of Agriculture, and other places where data are collected.
NCI investigators are also free to pursue high-risk and long-term studies
without jeopardizing their careers.
Because NCI orchestrates efforts to address difficult issues and has
a national perspective, it also has a responsibility to pay particular
attention to problems or questions that might otherwise go unattended,
says Dr. Hoover. For example, not many people would care to investigate
the high rates of lung cancer in Glynn County, Georgia, or colon cancer
in David City, Nebraska, which were identified by the cancer mortality
atlas. Since there is no concentration of chronic disease epidemiologists
in these areas, NCI needs to target studies at sites where these unusual
disease occurrences might otherwise go unattended and unnoticed. In addition,
because of its national position, the Program is able to collaborate with
other governments to study unusual cancer risks or exposures in various
countries.
NIH is predominantly a laboratory research facility and, having grown
up in that environment, DCEG is in an ideal position to lead in the area
of interdisciplinary studies. Being immersed in the largest basic science
program in the world, according to Dr. Hoover, gives the Division the
opportunity to interact and collaborate with various kinds of laboratory
scientists.
“These views of epidemiology in the government setting have led to our
creation of a broadly based group with rapid response capabilities, an
ability to exploit opportunities otherwise unaddressed, a responsibility
to tackle particularly difficult and high-risk studies, and a capacity
to focus on collaborative interdisciplinary studies,” says Dr. Hoover.
The development of the Human Genetics Program as a companion initiative,
and Dr. Klausner’s enthusiasm for NCI to become the world’s leader in
molecular epidemiology, are recent events contributing to strengthening
the Division and Institute programs in genetics and molecular epidemiology,
and in projects aimed at clarifying gene-environment interactions.
Important Developments
The Program has been responsible for numerous advances over the last 30
years. One of the earliest and most notable was the discovery in the late
1960’s by Dr. Fred Li and Dr. Joseph Fraumeni of a series of families
prone to diverse forms of cancer, most often childhood sarcomas and breast
cancer, known today as Li-Fraumeni syndrome. The families in these studies
have been evaluated periodically, and because of new technologies made
available in the late 1980’s, the cause of this rare syndrome was identified
as a germline mutation in the p53 gene. While the syndrome may
not have broad public health significance, p53 clearly has major
implications for common cancers in the general population and in our understanding
of the basic mechanisms of human carcinogenesis. As a major tumor suppressor
gene, p53 serves as a central “watchdog” gene that polices aberrant
cells.
Dr. Hoover says that the Program was also responsible for being either
the first or among the first to observe the following: (1) that estrogen
medication is a causative factor in breast cancer; (2) that there is an
association between herbicide use and non-Hodgkin’s lymphoma; and (3)
that fruit and vegetable intake protects against tobacco-related cancers.
The Program was also the first or among the first to identify (1) HTLV
as an oncogenic virus in human populations, and (2) the particular susceptibility
of the young to radiation-induced breast and thyroid cancers.
Program staff have also made significant advances in the development
of methods and techniques that have improved the way cancer epidemiology
is conducted. The first occupational linkage system was developed in the
late 1970’s by Dr. Shelia Zahm and became the prototype for assessing
exposures in occupational epidemiology. Historically, NCI has been the
place for the development of statistical methodologies to conduct multiple
contingency table analyses, and for modifications to regression techniques
that make these particularly strong tools for epidemiologic investigations.
In addition, new types of studies have been developed or refined by Program
scientists, like the case-cohort study and the kin-cohort study.
Evaluation of Program
“One of our biggest success stories is how the Program has changed the
way epidemiology is conducted by modernizing and bringing it into the
21st century,” says Dr. Hoover. He recalls that, years ago, investigators
developed questionnaires, coded records, hired interviewers, supervised
field workers, etc. These activities did not leave much time for epidemiology.
The Program introduced a new concept of hiring people who are trained
in these specific activities, thus freeing the epidemiologist to do epidemiology.
Dr. Hoover says, “The concept of support services through contracts revolutionized
how epidemiology is conducted, allowing more to be done, more quickly,
and the entire field has followed our lead.”
Another feather in the Program’s cap has been the happy marriage of laboratory
science and epidemiologic studies. “They complement each other, and the
opportunity to do them together, to circumvent the problems of both, has
been a major success story,” says Dr. Hoover.
The Future
Dr. Hoover believes the greatest challenge is to maintain the pace of
innovation in epidemiology and not to become complacent. For example,
the promise of molecular epidemiology is reflected in the fact that epidemiology
is the noun and molecular is the adjective. “I believe that studies in
this field need to be led by epidemiologists, and not by the many researchers
who lay claim to molecular epidemiology. Ultimately, the promise of the
field will only be realized by work which is high-quality epidemiology.”
Dr. Hoover feels there needs to be a balance in research programs with
respect to both subject matter and methodology. “In our current rush to
take advantage of opportunities in molecular epidemiology, we need to
remember there are proven traditional epidemiologic methods that have
produced and will continue to produce major findings in public health.
With respect to subject areas of research, our historically strong program
of family studies has put DCEG in good stead to lead the rapidly expanding
field of genetic epidemiology. However, just as we maintained a strong
genetics program when enthusiasm was high for the rapid development of
our environmental epidemiology programs, we need to continue to maintain
a balanced and comprehensive approach that pursues all areas of opportunity.
We need to continue our leadership in investigating the occupational,
nutritional, lifestyle, radiation, infectious, and other environmental
causes of cancer, while intensifying collaborations to utilize new technology
in genetics to help identify environmental carcinogens and gene-environment
interactions.”
Patricia S. Evans
|
|
The Human Genetics Program
 “The
largest advances in science often come when you least expect them,” says
Dr. Alfred Knudson, Acting Director of DCEG’s Human Genetics Program.
“When you specify everything you’re going to do in a plan, it tends to
diminish opportunities for major breakthroughs. Some research should be
open-ended, indicating that we haven’t reached the point where we can
prevent or treat all cancers successfully every time. Sometimes researchers
declare war on cancer as if they are building an atom bomb or going to
the moon. They forget that we do not yet have the basic knowledge required
by those projects.”
Discussing HGP apart from the Division itself is difficult, says Dr.
Knudson, because genetics is a pervasive feature of cancer, just like
the environment. Investigators working on environmental studies have become
very involved in genetic factors that might influence the response from
an environmental agent. In the same way, HGP is very interested in environmental
modifiers of genetic determinants. Dr. Knudson says that most cancer investigators
understand that there is some element of chance here, because mutations
can occur without any known cause and in a random fashion, but the probability
of mutations can be increased by the inheritance of predisposing genes
and by certain exposures. Although there are cancers that will always
occur because of spontaneous mutations, about 80 percent of cancers are
thought to be associated with environmental exposures, preexisting genetic
conditions, or both. HGP is concentrating on trying to identify predisposing
genes and understand how their interactions with environmental exposures
affect risk.
Important Developments
The work of Dr. Peggy Tucker and Dr. Jeff Struewing (HGP) in collaboration
with Drs. Patricia Hartge and Sholom Wacholder (EBP) on BRCA1 and 2 has
been very important. One of the major findings is that there is variation
in susceptibility from these genes resulting from environmental factors
or other genes. “If someone in a cancer family asked us what his or her
chances are of getting cancer, we have imprecise answers,” Dr. Knudson
said. “Based on the BRCA work, we now suspect that there is quite a range
of risks, and that we need better answers than we have now.”
The interaction of heredity and environment is well illustrated by skin
cancer. The discovery of the patched gene for the rare nevoid basal cell
carcinoma syndrome was a major finding with important implications for
understanding the very common nonhereditary basal cell carcinomas. The
collaboration of Dr. Alisa Goldstein of HGP with Dr. Michael Dean from
the Laboratory of Genomic Diversity in the Division of Basic Sciences
made this discovery possible. “Nevoid basal cell carcinoma is a rare syndrome,
but if you look at the garden variety basal cell carcinoma in people who
don’t have this syndrome, they also show patched gene mutations, which
are acquired after birth,” says Dr. Knudson. For both groups, the risk
of skin cancer is increased by sunlight.
Are there people who vary in their susceptibility to environmental factors?
The probability of a black person getting sun-related skin cancer compared
to a white person is small, while the probability of a white person who
moves from England to sunny Australia getting skin cancer is high. “We
know some answers,” says Dr. Knudson, “so it is not a surprise that the
environment does not fall evenly on all people.” However, sometimes susceptibility
is much more subtle. For example, people have different ways of metabolizing
environmental chemicals, a research area of great interest to Dr. Neil
Caporaso. Since some people appear to be particularly susceptible to tobacco-induced
lung cancer, while others are resistant, it may be possible to develop
interventions by identifying the mechanisms affecting risk.
Evaluation of Program
“Our Division is interested in populations of people with cancer,” says
Dr. Knudson. “Sometimes we can study them by focusing on high-risk families;
at other times, it’s better to look at their environmental exposures.
The BRCA1 and 2 study is an example of Division-wide collaboration, with
an evaluation of both genetic and environmental risk factors. The HGP
and the EBP work together, not only because we are interested in what
the other is doing, but because one group alone cannot solve many of the
cancer riddles. In this vein, the HGP is expanding to acquire more expertise
in the area of translational research through which our genetic findings
can be applied to clinical practice and counseling. In addition, the HGP
has created a Laboratory of Population Genetics, which is being headed
by Dr. Kenneth Buetow, that will be critical to our ability to identify
susceptibility genes and gene-environment interactions.”
The Future
What are the problems facing cancer genetics? How can genetics help us
to understand cancer, with respect to both the influence of the genes
themselves and the influence of the genes in response to the environment?
The genetics of cancer, in which the Division of Basic Sciences has great
expertise, concerns cells. The genetics of cancer also concerns the individual
(i.e., the person who develops cancer), which is the interest of the Division
of Clinical Sciences. In addition, the genetics of cancer concerns populations,
which is DCEG’s main focus. To study the genetics of cancer, one must
consider many areas, which means collaborating with other groups. “We
have always shared ideas across NCI. None of us works in a vacuum, nor
can we afford to do this,” says Dr. Knudson. “Divisions were not created
to ‘divide and conquer,’ but for convenience, so things don’t get massive
and out of control.” To ensure that there are properly trained scientists
in the field of cancer genetics, HGP has begun an interdisciplinary training
program for postdoctoral fellows. Coordinated by Dr. Dilys Parry, the
program is designed for persons who are acquainted with epidemiology,
statistics, laboratory research, or clinical oncology, but who wish to
have a broad working knowledge of all approaches and their relationship
to genetics.
“A lot has been accomplished in the prevention and treatment of cancer,
but still there is a significant upward trend in the incidence of certain
cancers,” says Dr. Knudson. “We know, for instance, that melanoma is on
the rise, because people are increasingly exposed to the sun’s rays, while
other tumors are increasing for reasons that are unclear. Lung cancer
keeps rising in women, although rates are leveling off in men, because
a high percent of people still smoke. On the other hand, there is a reduction
in some cancers, such as the stomach, which continues to go down in incidence
and in mortality.
“For some reason,” says Dr. Knudson, “our best record for cancer treatment
seems to be for the rare ones. Seventy-five percent of cancers in children
are cured. Young men with testicular cancer are cured at an astonishingly
high rate. Successes were unheard of when I was a medical student. We’ve
come a long way, but the common cancers still hang on.”
Dr. Knudson feels that new ideas are needed for treatment, early diagnosis,
and prevention of many cancers, especially pancreatic, colon, ovarian,
breast, and prostate cancer. The prospects are better for cancer patients,
but people are still dying in great numbers from these terrible diseases.
If scientists could figure out the major differences between a cancer
cell and a normal cell, according to Dr. Knudson, it might then be possible
to correct the cancer cell or kill it selectively. “If we could deactivate
or control the progression of malignant cells, we could extend many lives
before the critical genetic mutations take over,” says Dr. Knudson. “The
goal now may not be to eliminate all cancers, but rather to enable people
predisposed to cancer to get it 20 years later than is usual now. This
could result in dramatic improvements over the current situation. I think
both Dr. Hoover and I operate on the idea that cancer is something that
will always be with us, because cells make mistakes when DNA is replicated.
It’s a cruel hoax to say we will eliminate all cancer. Just shifting age
curves for cancer significantly would make a big difference. There are
people who die of lung cancer without ever having smoked, but they die
20 to 25 years later than smokers do. Prevention is the watchword here.
For other cancers, early diagnosis may be a rewarding approach. For example,
if colonoscopy could accomplish this for colon cancer, we need to make
it less expensive and available to all. Our basic aim should be to operate
at every level, and keep our base of knowledge growing so that we can
discover more ways to keep people alive, and in good health.”
Patricia S. Evans
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| TITLE 42 IN A NUTSHELL |
|
Title 42 is not the name of a new golf ball, restaurant, or latest best
seller, but is part of the U.S. Code of Federal Regulations dealing with
Public Health and Welfare. Around here, the most bandied about sections
are 209(g) and 209(h), and for those cognoscenti who want to delve deeper,
try http://www.fas.org/irp/offdocs/laws/usc42.html.
Actually, we have been using Title 42 for years, since it is the authority
under which we bring people on board into time-limited FTE-bearing appointments,
such as tenure-track investigators, staff fellows, and visiting scientists
and associates.
What is new is the expanded use of Title 42 for recruiting highly talented
and experienced scientists into the intramural and extramural research
programs. Although these appointments are still time-limited, the initial
period and subsequent unlimited renewals may be for as long as 5 years.
This new use of Title 42 will make us more competitive with respect to
salary, and reduce the time and rigamarole for bringing someone on board.
The annual stipend begins at the GS–13 level, and goes as high as Executive
Level I (currently $151,800). Of course, the higher the stipend, the higher
the level required for approval (Executive Level I needs the NIH Director’s
blessing). However, stipends ranging up to Executive Level IV (currently
$118,400) can be approved by Institute Directors, who may redelegate the
authority to Scientific Directors.
This new use of Title 42 complements the Senior Biomedical Research Service
(SBRS) and the Senior Executive Service (SES). Although each of these
personnel mechanisms permits salaries above those allowed under the General
Schedule of the Civil Service, both the SBRS and SES have a limited number
of positions. Expanded use of Title 42 not only avoids that restriction
but it offers greater flexibility at the programmatic level than these
other mechanisms for recruiting and retaining key individuals.
Besides allowing the recruitment of highly sought-after talent, Title
42 can also be used to hire staff scientists to carry out projects with
specific goals, such as setting up and operating a facility, and to retain
PHS Commissioned Officers upon their retirement from the Corps. In addition,
Civil Service workers who have maxed out at GS–15/10 may be converted
to Title 42 to obtain higher salaries. Like other appointments under Title
42, employees receive government benefits (e.g., creditable service toward
retirement, contributions for health insurance and pension, and participation
in the Thrift Savings Plan), but do not have the job protection or permanency
afforded under Civil Service.
Although all the policy and administrative wrinkles still need to be
ironed out, we are hopeful that this expanded use of Title 42 will become
an effective recruiting mechanism for enhancing the Division’s scientific
staff. Stay tuned. n Jim Sontag
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| CANCER MAPPING: CHARTING
A COURSE FOR HUMANKIND |
|
People have always been intrigued by maps. These flat graphic representations
of the earth or sky represent travel, exploration, and history. They are
the source of planning and dreaming. They get us from point A to point
B. The earliest maps that have survived are from Babylon and Egypt from
around 2500 B.C. Just as these maps give us a look at history, cancer
mortality maps allow us to visualize the patterns of cancer in various
parts of the country.
NCI’s first cancer mortality maps were published in two separate atlases.
The first was published in 1975 as the Atlas of Cancer Mortality for U.S.
Counties: 1950–1969, which was for whites only; and an Atlas of Cancer
Mortality Among U.S. Nonwhites: 1950–1969 was published in 1976. Subsequent
atlases were published in 1987 and 1990. Maps from these atlases identified
a number of “hot spots” around the country for various cancers, which
led to correlation studies with demographic and environmental variables
to help formulate etiologic hypotheses. This led, in turn, to case-control
studies in high-risk areas.
“These early atlases stimulated much analytic research,” says Dr. Susan
Devesa, Chief of the Descriptive Studies Section in the Biostatistics
Branch, whose responsibility it is to update the atlases. In 1994, NCI
began looking at ways to revise the atlases that would best serve researchers,
the target audience. “We gave a lot of thought to how best to develop
these maps, such as statistical methodology, colors, and presentations,”
said Dr. Devesa. “We wanted to make sure that these atlases would be giving
researchers the information they need to execute their work.”
Dr. Devesa asked a member of her staff, Mr. Dan Grauman, a computer specialist,
to develop the approaches to create the maps. Mr. Grauman’s background
in mathematics and statistics made him a natural to take on this task.
In addition, Mr. Grauman looked for sources of funding for the creation
of an Internet web site for the atlas. His efforts yielded $80,000 in
funding from the National Performance Review Innovation Fund (NPRIF) at
the Department of Commerce.
“We get death counts for each county each year for every type of cancer
across the country from the National Center for Health Statistics. We
had the complete statistics for years 1970 to 1992,” says Mr. Grauman.
The exceptions are Alaska and Hawaii, for which data are provided only
at the state level.
As Mr. Grauman developed the maps, Dr. Devesa began writing the text
in collaboration with Drs. Fraumeni and Hoover, as well as with Dr. William
Blot, the former Chief of the Biostatistics Branch. Toward the later stages
of the project, additional data were made available, and NCI made the
decision to expand the maps through 1994 to encompass 25 years. Corresponding
maps for 1950 to 1969 will also be included, as appropriate.
|
 |
|
What’s New This Time?
“This is the first time we will present data for the black as well as
white populations,” says Dr. Devesa. The earlier atlases presented data
on nonwhites as a group. Most of the maps will present rates for the State
Economic Areas (SEA), which are individual or groups of counties defined
by the Census Bureau. For the more common cancers, maps at the county
level will also be presented for whites.
The more than 140 maps, plus tables and text, will be available on DCEG’s
Internet web site. “These will be static maps,” says Mr. Grauman, “which
means the user cannot change any of the map parameters. It’s a ‘what you
see is what you get’ format.” Dr. Devesa and Mr. Grauman believe the site
will be used mainly by researchers, who will be able to download files
as needed. The database cannot be searched, but all county or SEA rates
can be identified for a particular cancer site or geographic location.
An interactive site for a more general audience is already being planned
with dynamic maps. This site will contain the entire United States
by county and/or SEA, as does the static map web site, but it will also
include statewide data. The user will be able to control parameters, such
as zoom, pan, and color, and make quantile selections. “Also,” says Mr.
Grauman, “users will be able to type in their zip code and get the cancer
rates for their county and comparison rates for their state and the United
States.” Nothing will be downloadable from this site, but searches can
be done.
Dr. Devesa says the new atlas should be ready by the fall, and that she
is working with the NCI Office of Cancer Communications on the distribution
of the atlas and notification of those groups that would be interested
in this type of information—like other government agencies, state health
departments, and cancer centers.
“It is our hope,” says Dr. Devesa, “that these maps will stimulate interest
on the part of researchers to find creative ways to help us learn more
about the geographic patterns of cancer mortality and risk factors contributing
to these conditions.”
Patricia S. Evans
|
| THANK YOU, DR. KLAUSNER |
|
On behalf of the staff of the Division of Cancer Epidemiology and Genetics,
the DCEG Committee of Scientists would like to express our gratitude to
Dr. Richard Klausner for his participation in our recent Town Meeting.
The meeting was inspiring, encouraging, and enjoyable. We appreciated
the knowledge, enthusiasm, and optimism about the opportunities in cancer
research that he communicated to us. We are also grateful for his willingness
to address, in a thoughtful manner, the diverse concerns raised by DCEG
staff. It helps us to have perspective about some of the issues we all
face. We hope that Dr. Klausner will consider returning and making the
Town Meeting an annual event. Thank You.
Sholom Wacholder
Chair, DCEG Committee of Scientists
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| RESEARCH VISION |
|
Nutritional Epidemiology Branch
As members of the newest Branch in the Epidemiology Program, we are in
the process of establishing research priorities and sharing our diverse
backgrounds and interests, which span nutrition, epidemiology, biochemistry,
and molecular biology. Although diet and nutrition are believed to be
related to a majority of human cancers, most of the specific causal and
protective factors remain to be identified. Their elucidation is complicated
by their interrelationships with each other and with other lifestyles.
However, the influence of diet and nutrition on cancer etiology is pervasive,
and most of the exposures are modifiable. We are excited by the challenges
before us.
Like the other intramural epidemiology branches, we have the responsibility
to provide scientific leadership, conduct higher risk and more difficult
studies, develop and take advantage of national and international resources,
and provide needed methodologic research. Our interests and expertise
are broader than just diet and nutrition, encompassing, for example, anthropometry,
physical activity, and endogenous hormones and growth factors. Because
of the extensive biological research underlying contemporary nutrition,
we are especially interested in multidisciplinary studies with metabolic
and/or molecular components.
There is the possibility of biases in dietary and nutrient information
collected after cancer diagnosis has been widely discussed, and we plan
to balance the large number of retrospective analyses in which we are
now involved with more prospective studies. We can take advantage of the
several cohorts in the Division on which we are working, such as the PLCO,
AARP, Radiation Technologists, Agricultural Workers, and BCDDP cohorts.
We feel that variability in exposure facilitates and strengthens dietary
studies, and hope to engage in more studies utilizing migrant populations
and international differences, such as the Asian-American study of breast
cancer, the Polish study of stomach cancer, and a study of cooking practices
in the European Prospective Investigation on Cancer and Nutrition.
Much of the methodology that has been developed for nutritional epidemiology
has relied more heavily on statistics than biology. Although these efforts
have been productive, we are excited about continuing our collaborations
with the biostatisticians in the Division to develop biologically meaningful
approaches. Chemoprevention trials have dominated NCI research in the
area of diet and cancer over the past 15 years; a more reasonable balance
is necessary. We recognize the complexities of this approach, and hope
that our epidemiologic work will increasingly contribute to the scientific
bases for decisions about future trials. In addition, we are continuing
followup of the Colorectal Polyp Prevention Trial, in which participants
were randomized to different diets rather than supplements.
More specifically, we will continue our focus on vegetables, fruits,
and micronutrients—trying both to answer public health questions about
the protective effects of vegetable and fruit intake as well as to identify
the active nutrients and/or phytochemicals. We are evaluating the roles
not only of the “antioxidant micronutrients,” but also of folate and other
B vitamins involved in methyl metabolism, which are essential to nucleic
acid synthesis and repair. We are intrigued by the challenging area of
energy balance, which involves caloric intake, physical activity, metabolic
efficiency, and body size and shape, and are aware that this is a rarely
evaluated, but probably a very important, exposure in the etiology of
breast and other cancers. In our research, we will be increasingly treating
body size and shape as variables that change during adult life.
Because of their extensive use in the United States, physiologic and
pharmacologic dosages of nutrient supplements, botanical, and specific
food additives, such as artificial fats and sweeteners, will continue
to be evaluated. Two additional research areas into which the Branch is
expanding are the effects and mechanisms of alcohol intake and the importance
of early life exposures. Nutrition-genetic interactions are a promising
area because of the high prevalence of exposure to dietary factors, the
expanding opportunities to assess genetic factors, and the limited research
already completed. We have been actively studying several carcinogens
produced during meat preparation and genetic determinants of their metabolism.
Folate, alcohol, and obesity are other specific areas where we are integrating
diet and genetics. We also want to look systematically at the various
cancers to determine (1) which may have been neglected in terms of dietary
studies, such as the lymphatic and hematopoietic cancers or early childhood
cancers; and (2) how universal certain dietary effects are, such as the
protection offered by vegetable and fruit intake. Efforts continue to
evaluate and improve dietary assessment methods, specific nutrient assays,
and hormone and growth factor measurement.
Because of our strong interest in diet, we feel it is critical to initiate
epidemiologic studies in which nutrition is the major focus, and not always
to rely on generic dietary assessment instruments being added to epidemiologic
studies with multiple objectives. We want to continue our multiple collaborations
with our colleagues in other branches, and wish to be actively involved
in the design, analysis, and interpretation of studies, as well as in
the development of dietary assessment instruments and administration of
laboratory components. We feel that our understanding of the biological
basis of nutrition, metabolism, and physiology provides an important contribution
to epidemiologic work. We recognize that we are a small Branch and cannot
always provide the expertise needed for the many projects with nutrition
components currently underway. Yet we hope, in the future, to be responsive
and to be involved in any major nutrition efforts initiated within the
Division.
Regina Ziegler
Occupational Epidemiology Branch
The Occupational Epidemiology Branch conducts epidemiologic investigations
in the workplace and other settings in which high exposures to occupational
and environmental agents occur. Our overall philosophy is to meld epidemiology,
quantitative exposure assessment, and biologic and genetic components
in investigations to identify chemical causes of cancer, to develop a
better understanding of carcinogenic mechanisms, and to improve epidemiologic
resources for use in epidemiologic research.
Several investigations with this interdisciplinary orientation are underway.
(1) A large case-control study of bladder cancer (1,500 cases and 1,500
controls) in Spain combines, for the first time in a study of this cancer,
the use of a sophisticated questionnaire for assessment of occupational
exposure. This questionnaire was recently developed by Branch industrial
hygienists along with a molecular component to investigate gene-environment
interactions. (2) An extension of the investigation of 75,000 benzene-exposed
workers in China is designed to evaluate risks of leukemia and non-Hodgkin’s
lymphoma over a wider range of benzene exposures than previously possible;
and to determine whether preneoplastic outcomes observed among workers
with benzene poisoning also occur at lower exposure levels. (3) A prospective
cohort study of 90,000 women in China provides an unusual opportunity
to investigate occupational and environmental exposures because of the
large number of women who work in industry and the heavy environmental
pollution in the study area. Collection of blood and urine from a large
fraction of the participants will be used to determine body burdens for
important occupational and environmental exposures and to assess gene-environment
interactions. (4) A retrospective cohort study of 8,000 miners is designed
to evaluate the risk of lung cancer from exposure to diesel exhausts.
This investigation will provide crucial information on an exposure that
is common among the general population. Miners have exposures, in order
of magnitude, higher than any other occupational group and present an
unusual research opportunity to clarify the carcinogenicity of this exposure.
The study employs a biospecimen component to relate metabolites of diesel
exhausts in blood and urine with indicators of biologic effects and a
computerized exposure assessment program recently designed by the Branch
investigators for use in the development of quantitative exposure assessment.
(5) The Agricultural Health Study is an ongoing investigation of over
90,000 pesticide applicators and their spouses designed to investigate
the role of pesticides and other agricultural exposures in the development
of cancer and other chronic diseases. During the next 5 years, the cohort
will be linked with vital statistics and tumor registries to obtain information
on cause of death and diagnoses of cancer. All participants will be contacted
for an interview to obtain additional information on agricultural exposures
and other cancer risk factors, and to collect buccal cells for assessment
of gene-environment interactions.
We intend to expand our efforts in the study of general environmental
exposures and the study of interactions with occupational exposures and
other risk factors. In particular, we seek opportunities in which occupational
and environmental exposures to suspected carcinogens can be evaluated
in the same study. Such investigations would allow us to evaluate cancer
risks over a wider range of exposures than is possible in studies focusing
on only occupational and environmental routes. They would also provide
direct information on a larger segment of the population. Occupational
and environmental exposures to the same agent often form a continuum,
with the lower levels of occupational exposure overlapping with the upper
end of general environmental exposures. This overlap can help to overcome
difficulties associated with epidemiologic studies in the environmental
arena. Exposures of current interest that might be amenable to this dual
approach include: nitrates and cancer (occupational exposures to farmers
and general population exposures in drinking water), and pesticides and
cancer (evaluation of occupational exposure in applicators and exposures
of the general population by remote sensing and GIS).
Because of a reliance on the cohort design, occupational investigations
in the past have often neglected other risk factors, such as diet, tobacco,
alcohol, microbes, and genetic factors. Even when nonoccupational factors
were included in an investigation of workplace exposures, the purpose
was usually to evaluate confounding. The ability to control for confounding
is important. An even stronger argument to obtain information on nonoccupational
factors in investigations of workplace exposures may be the opportunity
to evaluate the potential for effect modification. We have recently had
several clues to interactions that deserve further evaluation, such as
studies of non-Hodgkin’s lymphoma in relation to serum PCB levels, Epstein-Barr
virus infection, nitrates in the drinking water, and dietary factors.
Aaron Blair
Radiation Epidemiology Branch
The Radiation Epidemiology Branch (REB) conducts research to identify
and quantify the risk of cancer in various populations exposed to ionizing
and nonionizing radiation. Emphasis is placed on evaluating the risk of
radiation-associated cancer in terms of tissues at risk, dose response,
characteristics of the radiation exposure, and possible modifying influences
of other environmental and host factors. Because many REB studies involve
irradiated cancer patients, the Branch investigates the etiology of second
cancers, including the role of chemotherapy agents alone or in combination
with radiotherapy. Recently, we have become more involved in research
on the molecular characterization or “fingerprints” of radiation-related
tumors, and on the variation in radiogenic risk associated with cancer
susceptibility genes.
In the area of ionizing radiation, we are investigating the cancer risk
following radiation exposures from medical sources such as diagnostic
and therapeutic irradiation, including radiotherapy in combination with
chemotherapy and related drugs. We are evaluating occupational exposures,
focusing on high- and low-dose protracted exposure to external and internal
radiation, as well as environmental sources, particularly from the atomic
bombings in Hiroshima and Nagasaki, residential radon, nuclear waste,
and nuclear testing. Over the last few years, REB has been shifting its
emphasis toward occupational and environmental exposures, while expanding
its research program on multiple primary cancers. In addition, the public
and scientific interest in the long-term health effects from exposures
to nonionizing radiation has increased substantially over the last decade.
Results from epidemiologic studies have been inconsistent, and interaction
mechanisms, particularly at the cellular level, are not understood. REB
is conducting comprehensive epidemiologic investigations of childhood
leukemia and adult brain cancer which should improve our understanding
of the relationship between nonionizing radiation and carcinogenesis.
Over the next few years, REB will be focusing on several high-priority
research areas in carcinogenesis: evaluation of the effects of radioiodines,
chronic and low-dose radiation exposures, new chemotherapy, and radiotherapy
regimens in treating cancer; the interplay between radiation and other
exposures; the role of host susceptibility in radiogenic tumors; the effects
of exposure to nonionizing radiation; the integration of new physical
and biological methods for measuring radiation exposures; and methods
for incorporating uncertainties in dose estimates in dose-response analyses.
We also have identified three specific programs for future emphasis: UV
and skin cancer, childhood cancers, and gene-radiation interactions. These
projects will be conducted in collaboration with the Genetic Epidemiology
and Biostatistics Branches.
Skin cancer is the most common cancer in white populations worldwide,
and the incidence of both melanoma and nonmelanoma skin cancer has increased
over time. Sun exposure is a well-documented cause of melanoma and nonmelanoma,
but neither the patterns of risk nor the quantitative relationships are
well described. We are planning several epidemiologic studies on nonmelanoma
skin cancers, including an evaluation of time trends, and incidence patterns
in terms of age, ethnicity, gender, sun exposure, body location, and histopathology.
Case-control studies will be conducted to evaluate risk factors, including
sun exposure patterns, skin type, use of sun screens, chemical exposures,
diet, occupation, medical history, residential history, family cancer
history, ethnicity, and genetic susceptibility. In particular, we are
planning molecular epidemiologic studies on the mechanisms of genetic
susceptibility on the carcinogenic effects of ultraviolet radiation (e.g.,
PTCH and DNA repair genes).
Despite four decades of extensive investigation, the etiology of childhood
cancers is poorly understood. We have the opportunity to increase our
understanding of these important cancers by extending and expanding our
ongoing descriptive research, as well as conducting new analytic studies
initializing national registries in Sweden and clinical trial groups in
the United States. In addition, ongoing studies of childhood cancer survivors
will provide some insights into the risks and determinants of late effects,
including second cancers.
Several of the obstacles that make conducting studies of gene-environment
interactions so difficult can be minimized by studying individuals exposed
to ionizing radiation. The relatively accurate radiation exposure estimates
reduce misclassification, while the heterogeneity of exposure increases
the statistical power to detect interactions. Because large numbers of
people are needed to assess interactions, the large cohorts of irradiated
individuals already under study are prime candidates for these types of
investigations. Furthermore, groups with high attributable risks often
can be identified. REB has been striving to take advantage of the special
characteristics of radiation exposure for study of gene-environment interactions,
but we need to seize additional opportunities. Currently, we are conducting
population-based studies of ataxia-telangiectasia (AT); exploring the
interaction between radiotherapy and the Rb1 gene in a cohort of sporadic
and familial retinoblastoma patients; searching for specific mutations
in the p53 gene among patients developing second cancers; looking for
NF2 mutations in irradiated patients who develop schwannomas of the head
and neck following irradiation; and analyzing BRCA 1 and 2 mutations in
x-ray technologists who were diagnosed with cancer at an early age or
who developed two or more primary cancers. We also want to expand our
investigations of cancer risk in AT patients and heterozygotes, and in
x-ray technologists. In addition, we are considering evaluating other
REB-accessible study populations in our search for opportunities to investigate
genetic interactions in radiogenic tumors.
To improve communications and to plan for the future, we have founded
a journal club, established a second cancer working group and close collaborations
with genetic epidemiologists and molecular geneticists, and initiated
meetings with radiation researchers in other fields to discuss possible
new directions for REB. We are also making efforts to expand our collaborations
with other branches, divisions, institutes, agencies (e.g., Centers for
Disease Control [CDC]) and extramural centers. Finally, we are striving
to develop a radiation epidemiology training program at NCI that would
allow fellows to spend 2 years at the Radiation Effects Research Foundation
in Hiroshima, Japan.
Elaine Ron
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| SCIENTIFIC HIGHLIGHTS |
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Genetic Epidemiology Branch
Germline CDKN2A (p16) mutations have been detected in approximately
25 percent of melanoma-prone families. However, other genetic and/or environmental
factors likely influence disease expression. To identify these factors,
we evaluated the risk of melanoma in relation to clinical, environmental,
and genetic factors in 13 American families who had germline CDKN2A
mutations that cosegregated with melanoma.
Logistic regression analysis conditioning on family membership revealed
that complexion, dysplastic nevi, total number of nevi, and solar injury
each showed a significant association with melanoma, even after adjustment
for CDKN2A mutation. Although CDKN2A mutations confer substantial
risk for melanoma, sun-related exposures appear to further enhance the
risk. Identification of these clinical and environmental factors should
assist in further reducing the risk of melanoma in susceptible families
with CDKN2A gene mutations. (Goldstein, AM; Falk, RT; Fraser, MC;
Dracopoli, NC; Sikorski, RS; Clark, WH, Jr; Tucker, MA. “Sun-related risk
factors in melanoma-prone families with CDKN2A mutations,” J
Natl Cancer Inst 1998; 90:709–11.)
Lea Harty
Environmental Epidemiology Branch
Dr. Montserrat Garcia-Closas is working on a study entitled “Interactive
effects of genetic susceptibility and environmental factors on breast
cancer risk: A population-based study.” In April, she began the collection
of buccal cell specimens from approximately 5,500 cases and 5,500 controls
participating in an ongoing case-control study of breast cancer in the
states of Wisconsin, Massachusetts, and New Hampshire. This study will
evaluate genetic determinants of breast cancer and their interactions
with environmental and reproductive risk factors, focusing on polymorphisms
in enzymes involved in estrogen synthesis and metabolism.
Dr. Joanne Dorgan and her colleagues recently published a paper suggesting
a protective effect of carotenoids, specifically lutein-zeaxanthin and
lycopene, for breast cancer. (Dorgan, J; Sowell, A; Swanson, CA; Potischman,
N; Miller, R; Schussler, N; Stephenson, HE. “Relationships of serum carotenoids,
retinol, alpha-tocopherol, and selenium with breast cancer risk: Results
from a prospective study in Columbia, Missouri [United States],” Cancer
Causes Control 1998; 9:1, 89–97.)
Data collection for NCI’s follow-up study of women with augmentation
mammaplasty has recently been completed. This retrospective cohort study
identified nearly 13,500 women with cosmetic breast implants and 4,000
comparison subjects from 18 plastic surgery practices in 6 geographic
locations. Drs. Louise Brinton, Lori Brown, and Jay Lubin are currently
involved with data analyses. A special advisory group, headed by Dr. Mimi
Yu, recently met to review the study design and advise on approaches to
analysis, interpretation, and dissemination of the data. An ancillary
study has recently been initiated in Birmingham, Alabama, by Dr. Lori
Brown to define the prevalence of breast implant rupture. Dr. Brown, who
is on detail to DCEG from the Food and Drug Administration, recently published
two reviews: one on breast implant rupture, and the second on the connection
between silicone breast implants and autoimmune disease. (Brown, SL; Silverman,
BG; Berg, WA. “Rupture of silicone-gel breast implants: Causes, sequelae,
and diagnosis,” Lancet 1997; 350:1531–7; Brown, SL; Langone, JJ;
Brinton, LA. “Silicone breast implants and autoimmune disease,” J Am
Med Women’s Assn 1998; 53:21–4.)
Joanne Dorgan
Occupational Epidemiology Branch
A recent paper by Dr. Patricia Stewart and colleagues describes the development
of a new questionnaire with job-specific questions designed to improve
the quality of assessment of occupational exposures in community-based
studies. The procedures employ task-based and industry-based modules that
gather detailed information on materials and equipment, sensory descriptions,
engineering controls, and protective equipment. (Stewart, PA; Stewart,
WF; Siemiatycki, J; Heineman, EF; Dosemeci, M. “Questionnaires for collecting
detailed occupational information for community-based case control studies,”
Am Ind Hyg Assoc J 1998; 58:39–44.)
An extended followup of approximately 15,000 workers at an aircraft maintenance
facility revealed associations between exposure to organic solvents and
risk of non-Hodgkin’s lymphoma and multiple myeloma among men and women.
Exposure to solvents and other chemicals also increased the risk of breast
cancer among women. (Blair, A; Hartge, P; Stewart, PA; McAdams, M; Lubin,
J. “Mortality and cancer incidence of workers at an aircraft maintenance
facility exposed to organic solvents and other chemicals: Extended follow-up,”
Occup Envir Med 1998; 55:161–71.)
A recent book from an IARC workshop held in 1996 focuses on methodologic
issues associated with incorporating biomarkers into epidemiology investigations
of cancer. Dr. Nat Rothman served as one of the editors, and a number
of DCEG investigators contributed to individual chapters. (“Application
of biomarkers in cancer epidemiology,” in IARC Scientific Publ. No.
142. Toniolo, P; Boffetta, P; Shuker, DEG; Rothman, N; Hulka, B; Pearce,
N, eds. IARC: Lyon, France, 1997.)
Aaron Blair
Radiation Epidemiology Branch
Dr. Ethel Gilbert and Dr. Jay Lubin, Biostatistics Branch, served as
members of the National Research Council Committee on the Health Risks
of Exposure to Radon (BEIR VI). The recently released report concluded
that smokers who are exposed to radon appear to be at an even higher risk
for lung cancer because the effects of smoking and radon are more powerful
when the two factors are combined. Indoor radon contributes to about 12
percent of lung cancer deaths each year in the United States.
Studies of childhood acute lymphoblastic leukemia (ALL) and electromagnetic
fields (EMF) have produced three recent publications:
1) Case-control study of childhood acute lymphoblastic leukemia and
residential radon exposure. In contrast to prior ecologic studies
of radon and childhood leukemia, the results from this analytic study
provide no evidence for an association between indoor radon exposure and
childhood ALL. (Lubin, J; Linet, M; Boice, J; Buckley, J; Conrath, S;
Hatch, E; Kleinerman, R; Tarone, R; Wacholder, S; Robison, L. “Case-control
study of childhood acute lymphoblastic leukemia and residential radon
exposure,” J Natl Cancer Inst 1998; 90:294–300.)
2) Association between childhood acute lymphoblastic leukemia and
use of electrical appliances during pregnancy and childhood and residential
wire codes. Increased risks for childhood ALL were associated with
several appliances. However, the inconsistency in the dose-response patterns
for many appliances, reporting and selection bias, and the lack of an
effect for measured 60-hertz magnetic fields or wire codes in the companion
study, must be considered before ascribing these associations to exposures
from magnetic fields. (Hatch, E; Linet, M; Kleinerman, R; Tarone, R; Severson,
R; Hartsock, C; Haines, C; Kaune, E; Friedman, D; Robison, L; Wacholder,
S. “Association between childhood acute lymphoblastic leukemia and use
of electrical appliances during pregnancy and childhood,” Epidemiology
1998; 9:234–245.)
3) Reproducibility and relationship with measured magnetic fields
and residential wire codes. Misclassification of wire code categories
was determined not to be a major source of bias in the study of childhood
ALL and magnetic field exposure. (Tarone, R; Kaune, W; Linet, M; Hatch,
E; Kleinerman, R; Robison, L; Boice, J; Wacholder S. “Residential Wire
Codes: Reproducibility and relationship with measured magnetic fields,”
Occup Envir Med 1998; 55:333–339.)
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| NEWS FROM THE TRENCHES |
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Genetic Epidemiology Branch
Dr. Neil Caporaso was the Chairperson for a special educational session
entitled “Molecular Epidemiology: Current Perspectives” at the annual
meeting of the American Association for Cancer Research (AACR) in New
Orleans in March. The purpose of the session was to encourage interaction
among basic, clinical, and population researchers. During the session,
Dr. Rashmi Sinha, Nutritional Epidemiology Branch (NEB), spoke on “Transitional
Studies: The Link Between the Laboratory and Population Studies”; Dr.
Lea Harty, Genetic Epidemiology Branch (GEB), on “The Case-Control Approach
to Molecular Epidemiology”; and Dr. Nathaniel Rothman, Occupational Epidemiology
Branch (OEB), on “Cohort Studies: Evaluating Exposure, Early Biologic
Effects, and Susceptibility.”
The Melanoma Consortium was hosted by GEB on June 1 and 2. The meeting
included several groups collaborating on family studies of melanoma. Investigators
from Australia, Canada, Great Britain, Italy, the Netherlands, Sweden,
and the United States attended the meeting.
Occupational Epidemiology Branch
Dr. Dalsu Baris chaired a session on neurodegenerative diseases, neurobiological
disorders, and electromagnetic field (EMF) exposures at the EMF Science
Review Symposium in San Antonio, sponsored by the National Institute of
Environmental Health Sciences (NIEHS).
Dr. Ken Cantor and Dr. Mary Ward served on a DHHS subcommittee to identify
research and information needs regarding drinking water and health effects.
Chaired by Dr. Richard Jackson, Director, National Center for Environmental
Health, CDC, the committee included representatives from HHS agencies
(NIEHS, NCI, National Institute for Occupational Safety and Health [NIOSH],
Indian Health Services, FDA) and other Federal agencies, including EPA
and Department of Agriculture. The committee published its recommendations
in a report, “Drinking water and human health: The role of the U.S. Department
of Health and Human Services.”
Dr. Aaron Blair and Dr. Patricia Stewart served as members of an International
Agency for Research on Cancer (IARC) Working Group in Lyon, France, to
evaluate a number of industrial chemicals for Volume 71 in the series
of IARC Monographs on Evaluation of Carcinogenic Risks to Humans.
Congratulations to Dr. Michal Freedman, who completed requirements for
her Ph.D. in Epidemiology from Johns Hopkins School of Hygiene and Public
Health. The title of her dissertation was “A population-based case-control
study on the association between nitrates in drinking water and non-Hodgkin’s
lymphoma.”
A new Computer-assisted Personal Interview (CAPI) program has been developed
for a case-control study of bladder cancer in Spain. This system, developed
by Westat for the Occupational Epidemiology Branch investigatory team
led by Drs. Dosemeci, Rothman, and Silverman, incorporates the job-specific
modules developed by Dr. Stewart into the CAPI program. This program can
be readily modified for other investigations. Contact the OEB if you wish
to learn more about the system for your own studies.
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| ADMINISTRATIVE UPDATES |
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Research Contracts Branch
As a result of a recent legal opinion, NCI staff who have project officer
responsibilities with a proposing institution are now precluded from serving
on a Technical Evaluation of Proposal committee for the R&D process since
this could be viewed as conflict of interest. The “Orange Book” (Section
II, A, Part 1: Research and Development, page II–A2) has been changed
to reflect this new restriction, as follows: “In addition, NCI staff are
prohibited from reviewing a proposal from an institution where he or she
has Project Officer responsibilities.”
Changes have also taken place within the Research Contracts Branch that
will enable the staff to better serve the changing program needs of the
National Cancer Institute. The new organization is shown below.
Epidemiology and Support Section
(Previously, Cancer Etiology Contracts Section)
Chief: Beverly L. Wyatt
Deputy Chief: Sharon A. Miller
Divisions Supported: Division of Cancer Epidemiology and Genetics; Division
of Clinical Sciences; Division of Basic Sciences; Office of the Director,
NCI
Treatment and Biology Section
(Previously, Treatment Contracts Section)
Chief: Nancy E. Coleman
Deputy Chief: Richard Hartmann
Divisions Supported: Division of Cancer Treatment and Diagnosis; Division
of Cancer Biology
Prevention, Control and Population Sciences Section
(Previously, Prevention and Control Contracts Section)
Chief: Jeannette J. Johnson
Deputy Chief: Susan Hoffman
Divisions Supported: Division of Cancer Prevention; Division of Cancer
Control and Population Sciences
Purchasing and Support Acquisition Section
(Previously, Purchase and Support Contracts Section)
Chief: Todd Cole
Area Supported: Simplified Acquisitions (<$100,000) and Commercial Item
Acquisitions (<$5 million) for all of NCI
Sharon A. Miller
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| SPECIAL AWARDS |
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The following awards were made by Dr. Klausner to staff members at the
DCEG Town Meeting in February.
Government Service Longevity Awards (certificate and pin)
Ms. Denise Duong
Radiation Epidemiology Branch (not pictured)
In recognition of 10 years of service in the Federal Government
Ms. Jennifer Donaldson
Biostatistics Branch
In recognition of 20 years of service in the Federal Government
HHS Quality of Work Life Award (certificate)
Dr. Elaine Ron
Radiation Epidemiology Branch
For her efforts to improve the overall workplace environment by strengthening
communications with employees and for her promotion of communication skills
among women scientists of DCEG.
Cowinners of the 1997 DCEG Mentoring Award (plaque and a $3,000
Special Act Award)
Dr. Shelia Zahm
Occupational Epidemiology Branch
Citation on the Plaque: Dr. Shelia Zahm possesses all the qualities of
an outstanding mentor. Her knowledge of epidemiology is exceptional, and
she willingly dispenses her wisdom with patience and enthusiasm. Dr. Zahm
is always available to discuss projects and answer questions. Her reinforcing
and reassuring manner inspires fellows to strive for excellence. Her colleagues
learn from her the value of encouraging others and seizing opportunities
for challenging and rewarding work. Dr. Zahm is a special role model,
and well deserving of the Mentoring Award.
Dr. Dilys Parry
Genetic Epidemiology Branch
Citation on the Plaque: Dr. Dilys Parry has mentored fellows for almost
20 years. She spearheaded NIH’s Interinstitute Medical Genetics Training
Program and developed NCI’s Cancer Genetics and Epidemiology Training
Program. For the new NCI Program, Dr. Parry is organizing a series of
didactic courses focusing on clinical, molecular, and population genetics
that are germane to fellows and other scientists at all levels. She has
a genuine interest in the well-being of fellows, and her door is always
open for discussions about science, career plans, and life in general.
These positive characteristics along with her level-headed and encouraging
attitude make Dr. Parry a most deserving recipient of the Mentoring Award.
1997 Outstanding Paper by a Fellow in DCEG (plaque and $1,000
cash award)
Dr. Lea Harty
Genetic Epidemiology Branch
Dr. Harty received this prestigious award for her paper entitled “Alcohol
Dehydrogenase 3 Genotype and Risk of Oral Cavity and Pharyngeal Cancers,”
which reported risks of oral cancer to be highest among heavy drinkers
homozygous for the 1–1 genotype of alcohol dehydrogenase-3 (ADH3). ADH3
is a genotype that appears to rapidly metabolize ethanol to acetaldehyde,
for which there is evidence of carcinogenicity in laboratory animals.
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| DCEG PEOPLE IN THE
NEWS |
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Dr. Wong-Ho Chow and Dr. Debra Silverman, Occupational
Epidemiology Branch (OEB), were accepted into the American Epidemiological
Society, a prestigious organization of senior-level epidemiologists.
Ms. Gloria Gridley, Biostatistics Branch, recently received the
Distinguished Federal Employees Award from Blue Cross-Blue Shield for
her ongoing role in promoting science in the schools and the community.
She is a member of the Quantitative Literacy (QC) Committee of the Washington
Statistical Society and the Graduate Women in Science’s “sisters in science“
(SIS) program. Ms. Gridley has been involved in a variety of efforts to
promote science, including teaching statistics, mentoring, serving on
the Rockville Science and Technology Commission as a mayoral appointee,
and judging Fairfax and Montgomery County science fairs. Most recently,
Ms. Gridley paired students in the sixth grade with scientist coaches
to help them prepare competitive science fair projects to enter the Montgomery
County Science Fair, in which one of these students was awarded first
prize in zoology.
Dr. Neely Kazerouni, Nutritional Epidemiology Branch, was named
as the DCEG representative to the newly formed NIH Predoctoral Fellows
Committee.
Dr. Sandra Petralia, OEB, and Dr. Frank Groves, Biostatistics
Branch, have replaced Dr. Lea Harty, Genetic Epidemiology Branch, and
Dr. Mary Ward, OEB, as DCEG representatives to the NIH Fellows Committee.
Dr. Shelia Zahm has been appointed Deputy Director of DCEG. She
joined NCI as a Staff Fellow in 1980, and has been Deputy Chief of the
Occupational Epidemiology Branch since 1996. Dr. Zahm’s research in cancer
epidemiology has been focused on detection of high-risk occupational groups
and effects of exposure to pesticides and others chemicals, with particular
emphasis on the etiology of lymphomas.
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| COMINGS...
GOINGS... |
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Dr. Andrew Bergen, a Fellow in the Human Genetics Program, is
working on a review of smoking phenotypes and related factors, and is
evaluating various cohorts for a possible genetic study of susceptibility
loci associated with nicotine dependence. He is located in EPN/400 and
can be reached at 402–9529.
Dr. Christina Bromley, a Fellow in the Human Genetics Program,
is working with Dr. Goldstein on a melanoma data set to evaluate different
methodologies to investigate clustering. This effort will help to establish
the best approaches to analyze clustering among melanoma families. Dr.
Bromley received a Ph.D. from the University of Nebraska. She is located
in EPN/400 and can be reached at 402–9638.
Dr. Naoko Ishibe, a Human Genetics Program Fellow, is studying
the characteristics of bronchioalveolar lung carcinoma at the National
Naval Medical Center. In particular, she is evaluating how its presentation,
risk factors, and outcome differ from adenocarcinoma of the lung. Dr.
Ishibe is also participating in a study of chronic lymphocytic leukemia
to contrast the epidemiological and clinical features of familial cases
with their sporadic counterparts, as well as the pattern and occurrence
of cancer in the families. She is located in EPN/400 and can be reached
at 435–3348.
Mr. Dave Kaufman, a Fellow in the Laboratory of Population Genetics
(LPG), is working with Dr. Jeff Struewing on BRCA1 and BRCA2 mutations
in high-risk families, as well as searching for evidence of a third breast
cancer gene. Mr. Kaufman is working on a Ph.D. in Genetic Epidemiology
at Johns Hopkins University. He is located in EPN/531 and can be reached
at 435–4905.
Ms. Jenny Kelley recently joined the LPG as the Technical Laboratory
Manager. She comes to DCEG from The Institute for Genomic Research (TIGR),
where she set up high-throughput automated DNA sequencing, organized the
laboratory, hired and trained the staff, and conducted research and development.
In LPG, she will organize the laboratory and train the staff, as well
as serve as a technical resource to investigators developing their own
research activities. In addition, Ms. Kelley will be a valuable resource
for NCI’s Advanced Technology Center, which will perform high-throughput
DNA genotyping and sequencing. Ms. Kelley is located in Building 9 and
can be reached at 435–8954.
Dr. Kai-Li Liaw, after 6 years at the NCI, said farewell to the
Environmental Epidemiology Branch and accepted an Assistant Professorship
in the Department of Epidemiology at the University of Pittsburgh.
Mr. Roberto Minutillo, who recently joined the ARC as an Administrative
Officer, is an Administrative Career Development (ACD) Intern with the
NCI and will be in this position for 9 months. Mr. Minutillo began his
ACD internship with the Grants Administration Branch and the Research
Contracts Branch. Before ACD, Mr. Minutillo was a Purchasing Agent in
the Clinical Center. He is located at EPN/539 and can be reached at 594–7210.
Dr. Dirk Moore, who is from the Statistics Department at Temple
University, is spending a 6-month sabbatical in the Biostatistical Branch.
He has degrees in Mathematics, Biostatistics, and Biology. Dr. Moore spent
a year in Japan at RERF and 5 years in an adjunct position with the Fox
Chase Cancer Center. In the Biostatistics Branch, he is working on methods
to estimate the cumulative risk of breast cancer by a given age for carriers
and noncarriers of mutations in the BRCA1 and BRCA2 genes. The estimates
are based on the kin-cohort design used by DCEG scientists to study cancer
risk and mutation carriers in Ashkenazi Jews. Dr. Moore is located in
EPN/431 and can be reached at 496–4155.
Dr. Andrew Olshan, an Associate Professor of Epidemiology at the
University of North Carolina, has joined the Occupational Epidemiology
Branch for a 6-month sabbatical. Dr. Olshan is interested in methods of
exposure assessment for community-based studies, childhood cancer, and
gene-environment interactions
Dr. Susan Sieber has been appointed Associate Director for Special
Projects in the Office of the Director, NCI. In this new position, Dr.
Sieber will be responsible for assisting Dr. Klausner in developing policy
related to the intramural and extramural functions of NCI, serving as
a liaison between the Director’s office and advisory groups, and coordinating
NCI activities in a variety of areas. Dr. Sieber was Deputy Director of
DCEG.
Mr. Mike Stevens, a student at Montgomery College, has joined
the Environmental Epidemiology Branch through the STEP program and will
be providing administrative and clerical support to the Branch. He is
located at EPN/443 and can be reached at 496–1693.
Dr. Louise Wideroff (Environmental Epidemiology Branch) and Dr.
Andrew Freedman (Genetic Epidemiology Branch) recently joined the
Applied Research Branch in the Division of Cancer Control and Population
Sciences, NCI.
Dr. Tamara Zemlo has joined the Environmental Epidemiology Branch
through the Division of Cancer Prevention Fellowship Program. She is working
with Dr. Mark Schiffman on determining if HPV positivity predicts recurrence
and progression of cervical cancer precursor lesions. She received a Ph.D.
from the University of Wisconsin, writing her dissertation on cellular
transformation by the human papillomavirus, and an M.P.H. from the Harvard
School of Public Health. Dr. Zemlo is located at EPN/443 and can be reached
at 435–3976.
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| OBITUARY |
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The Genetic Epidemiology Branch recently lost a close collaborator of
20 years, Dr. Wallace H. Clark, Jr., who died in November 1997. At the
time of his death, Dr. Clark was a distinguished pathologist affiliated
with Beth Israel Hospital/Harvard Medical School and the Pigmented Lesion
Study Group at the University of Pennsylvania. He was dedicated to the
study of the neoplastic process, with a particular emphasis on melanoma,
and developed the now-standard microstaging system for melanoma lesions
(the Clark Classification System). He was the coauthor of over 135 scientific
articles, 2 of which were recently published: “Problems with lesions related
to the development of malignant melanoma: Common nevi, dysplastic nevi,
malignant melanoma in situ, and radical growth phase malignant melanoma”
(Clark, WH, Jr; Tucker, MA. Hum Pathol 1998; 29[1]:8–14), and “Atypical
melanocytic nevi of the genital type with a discussion of reciprocal parenchymal-stromal
interactions in the biology of neoplasia” (Clark, WH, Jr; Hood, AF; Tucker,
MA; Jampel, RM. Hum Pathol 1998; 29[1] Suppl 1: S1–S24). His keen
insight, enthusiasm for science, and indomitable good nature will be missed.
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| CALENDAR OF EVENTS |
|
Following is a schedule of upcoming events of particular interest to
DCEG.
| Date |
Meeting |
| June 9–10 |
General Motors Cancer Research Foundation Conference |
| June 18 |
Senior Advisory Group 1–4 p.m., EPN/H |
| June 22 |
DCEG Women Scientists Brown Bag Lunch Noon, EPN/H |
| July 9 |
Senior Advisory Group 1–4 p.m., EPN/H |
| July 13 |
Board of Scientific Counselors–A |
| July 23 |
Senior Advisory Group Retreat Glenview Mansion, Rockville |
| August 13 |
Senior Advisory Group 1–4 p.m., EPN/H |
| September 9–11 |
National Cancer Advisory Board |
|
“The
Program’s vision mirrors that of the Division,” says Dr. Hoover. “Part
of this derives from the fact that, until recently, the current Division
was the Program. However, part of the similarity derives from the very
nature of epidemiology. It calls for a large, broad-based program that
affords investigators the opportunity and resources to go where there
is a ‘natural experiment.’ These rare events require studies of very large
groups of people on location. This sort of opportunity tends to mandate
the need for a national program.”