Estimating absolute risk of cancer can have profound implications for targeted prevention strategies and clinical decision making. On May 20, more than 100 experts met in Washington, DC, for a workshop about cancer risk prediction models. “This interdisciplinary workshop broke ground by bringing together the cancer risk prediction modeling community for the first time and helping identify the research steps needed to move this field forward,” noted Andrew Freedman, Ph.D., cochair of the workshop from NCI’s Division of Cancer Control and Population Sciences (DCCPS). The workshop was cosponsored by NCI’s Division of Cancer Epidemiology and Genetics (DCEG), DCCPS, and the NCI Office ofWomen’s Health.

The workshop included four sessions on risk prediction models: applications, development and implementation, evaluation and validation, and predicting germline mutation carrier status. Poster sessions presented models in use or under development, including models for melanoma and breast, lung, colorectal, and prostate cancer, and for genetic susceptibility to colorectal and breast cancer. As noted by DCEG’s Ruth Pfeiffer, Ph.D., cochair of the workshop, “After intensive discussions between model developers and clinicians, there was consensus that model performance should be judged in the context of specific applications and that further methodological research is needed to develop criteria for model assessment.”

Priorities for future research include identifying cancer sites for which new risk prediction models are useful, finding ways to improve current and future cancer risk prediction models by incorporating new clinical and biological markers, and providing data resources and study populations for modeling and validation. “The meeting was valuable in describing useful applications for risk models with modest discriminatory power and applications such as screening for which more discriminating risk models are needed,” said DCEG’s Mitchell Gail, M.D., Ph.D., who 15 years ago developed a widely used breast cancer risk prediction model.

DCEG HOLDS MOLECULAR EPIDEMIOLOGY COURSE

This winter, approximately 45 DCEG staff members participated in a 50-hour Molecular Epidemiology Course that was held weekly, from January through April 2004. The course, intended primarily for DCEG and Core Genotyping Facility (CGF) tenure-track investigators, staff scientists, and fellows, has become a regular part of DCEG’s educational activities. “The goal of the course is to train junior research staff in the design, implementation, management, and analysis of molecular epidemiology studies within the NCI,” said Demetrius Albanes, M.D., Chief of DCEG’s Office of Education (OE). The course also deals with how to collaborate effectively with the CGF and other laboratories.

In addition to didactic sessions and laboratory visits, students are asked to integrate methodological and analytical components into the preparation and presentation of a concept that is based on course material. Students are encouraged to seek funding for these proposals. DCEG first offered the Molecular Epidemiology Course in 2000. Nathaniel Rothman, M.D. (Occupational and Environmental Epidemiology Branch), and Jim Vaught, Ph.D. (Office of the Director), served as the backbone for this year’s course. Participants benefited from their careful planning, contributions during each session, and insightful evaluations of concept proposals at the end of the session. Kristin Kiser, M.H.A. (OE), also provided coordination for the course.

Recent data from a DCEG study of industrial workers found an association between formaldehyde exposure and leukemia. The study, published in the Journal of the National Cancer Institute, showed that workers exposed to high peak levels of formaldehyde had a 3.5-fold increased risk of dying from myeloid leukemia compared to workers exposed to low peak levels. Leukemia risk also rose with average exposure intensity and duration, though to a lesser extent. “This analysis addressed the unresolved question of whether formaldehyde is a human carcinogen,” said Aaron Blair, Ph.D., senior author of the paper and Chief of the Occupational and Environmental Epidemiology Branch (OEEB).

The study followed a cohort of 25,619 persons employed prior to January 1966 and through December 1994 at one of 10 U.S. industrial plants. The cohort, assembled in the 1980’s, is the largest study of industrial workers exposed to formaldehyde. Formaldehyde is a flammable and colorless gas used in the production of many important commercial products, including resins, molding compounds, photographic film, textiles, decorative laminates, and plywood. It is also used as a bactericide and a tissue preservative. The U.S. National Institute for Occupational Safety and Health estimated that 1.5 million U.S. workers were exposed to formaldehyde from 1981 to 1983.

The exposure assessment, led by Patricia Stewart, Ph.D., industrial hygienist and senior investigator in the OEEB, enabled the researchers to look at peak exposure, average exposure intensity, cumulative exposure, and exposure duration. “Having four metrics of exposure was a unique feature of this study,” said Michael Hauptmann, Ph.D., lead author of the paper and tenure-trackinvestigator in the Biostatistics Branch. “Examining different exposure variables helped us get a fuller and more accurate picture.” Data were also gathered on exposure to many other widely used chemicals in the plants.

Although formaldehyde’s leukemia-inducing mechanisms are unclear, there have been reports that such exposure may cause micronuclei, DNA protein crosslinks, sister chromatid exchanges, and chromosomal aberrations in human peripheral lymphocytes. In addition, previous studies of professional groups such as embalmers, pathologists, and anatomists have suggested an association with leukemia, but these studies lacked detailed exposure assessments. DCEG researchers are currently evaluating data from a nested case-control study of leukemia among embalmers with quantitative exposure assessment. At issue is whether formaldehyde is capable of reaching leukemia target cells, so NCI investigators are considering studies to evaluate genetic and epigenetic changes in blood samples from formaldehyde-exposed populations. “Molecular alterations in the peripheral blood cells of such groups will provide important evidence on whether there is a causal association with leukemia,” said Dr.Hauptmann.

"The study, published in the Journal of the National Cancer Institute, showed that workers exposed to high peak levels of formaldehyde had a 3.5-fold increased risk of dying from myeloid leukemia compared to workers exposed to low peak levels."

Although Drs. Blair and Hauptmann cite a few challenges with the study—such as potential exposure misclassification and lack of exposure information for 1980 to 1995—they think it is unlikely that the leukemia excess is due to a factor other than formaldehyde. This is because exposure misclassification was most likely nondifferential with respect to cause of death, only a few workers included in the study were still employed after 1980, and formaldehyde exposures have decreased substantially over the past two decades.While it is possible that the finding is due to chance, the study had a larger number of leukemia deaths for evaluation than any other investigation. NCI investigators presented an updated analysis of solid cancers in a second paper, which appeared in the June 15, 2004, issue of the American Journal of Epidemiology. Important findings include increasing risks for nasopharyngeal cancer with average exposure intensity, cumulative exposure, duration of exposure, and peak exposure to formaldehyde (based on only nine deaths) and no association for lung cancer for any of the four metrics of formaldehyde exposure (based on 744 lung cancer deaths). The finding for nasopharyngeal cancer is consistent with experimental studies linking formaldehyde exposure to nasal cancer in rodents.

Although occupational formaldehyde exposures have declined, new sources of exposure exist, so delineating the health risks remains a priority. For instance, formaldehyde accounts for about two-thirds of the total hazardous air pollutant emissions from natural-gas-fired turbines, which may be used as a future power source.

In June, the International Agency for Research on Cancer upgraded formaldehyde to “carcinogenic to humans.” Citing new evidence, including the above NCI research, the expert panel, which included Dr.Hauptmann, stated that the previous evaluation of formaldehyde as “probably carcinogenic to humans” was based on the smaller number of studies available at the time. The U.S. Environmental Protection Agency is also currently updating its assessment of health risks from formaldehyde exposure, and DCEG’s work as well as other reports from recently updated occupational cohorts will be used in the process.

—Maria Sgambati, M.D.

RADIATION EPIDEMIOLOGY COURSE DRAWS INTERNATIONAL AUDIENCE

Approximately 80 individuals with an interest in the health effects of radiation exposure attended a 10-day Radiation Epidemiology Course held in Rockville, MD, in May. The course, sponsored by the Radiation Epidemiology Branch (REB), attracted attendees from across the United States and around the world, including Japan, Korea, Russia, Ukraine, Belarus, Israel, Sweden, Great Britain, the Netherlands, Germany, and France. The audience included researchers, clinicians, and policymakers who represented such disciplines as epidemiology, biostatistics, basic radiation sciences, cancer biology, radiation oncology, radiation protection, and risk estimation and management. “With these diverse backgrounds and aims came diverse points of view, and most talks were accompanied by spirited discussion,” said Peter Inskip, Sc.D. (REB), who organized the workshop. “The hope is that these interactions will help bridge the gaps between disciplines and stimulate new lines of research.” The workshop addressed topics such as radiation physics and dosimetry, radiation chemistry, radiobiology and radiation oncology, and radiation epidemiology. Epidemiology discussions centered on studies of Japanese atomic bomb survivors, medically irradiated populations, and persons with occupational or environmental radiation exposures.

On March 25, 2004, Harvey Checkoway, Ph.D., M.P.H., visited DCEG as a Distinguished Lecturer in Occupational and Environmental Epidemiology. Dr. Checkoway is Professor of Environmental and Occupational Health Sciences at the University of Washington School of Public Health and Community Medicine, with a joint appointment in the Department of Epidemiology. He also directs the university’s Superfund Basic Research Program and Training Grant in Environmental and Molecular Epidemiology, both funded by the National Institute of Environmental Health Sciences. His well-known book, Research Methods in Occupational Epidemiology, is one of the few epidemiologic texts that deals specifically with occupational issues. His current research ranges from studies on silica, silicosis, and lung cancer among diatomaceous earth industry workers, to environmental and genetic risk factors for Parkinson’s disease, to cancer risks among textile workers in Shanghai. Dr. Checkoway’s lecture addressed “Investigating straightforward and not-so-straightforward etiologic hypotheses in occupational cancer epidemiology.”

The Occupational and Environmental Epidemiology Branch (OEEB) launched the Distinguished Lectures series in 2002. Each year, three or four prominent scientists visit for two days to give lectures and meet with DCEG staff to discuss issues and challenges of mutual interest. The objectives of the series are to expand and intensify contacts between intramural and extramural investigators, provide an opportunity for junior staff to meet with distinguished scientists, and highlight research opportunities in occupational and environmental cancer. “Having these eminent scientists as guest lecturers has been a great privilege for the OEEB and DCEG,” said Dalsu Baris, M.D., Ph.D., organizer of the 2004 series. “We have had stimulating discussions with them through meetings and seminars and have immensely benefited from their knowledge, experience, and wisdom.”

For more information on DCEG’s Distinguished Lecture series, please visit:
http://dceg.nci.nih.gov/occu-DistinguishedLectures.html.

MIMI YU RECOGNIZED FOR HER CONTRIBUTIONS TO DCEG

Dr. Mimi Yu, a professor in the Department of Epidemiology at the University of Southern California School of Medicine, received a DCEG Special Recognition Award in March 2004. The award was given in appreciation for Dr. Yu’s many contributions to the Division while serving on the NCI Board of Scientific Counselors from 1998 to 2003. In addition to the usual heavy workload of site visits, she also chaired the advisory group for the Breast Implant Study and the Data Safety Monitoring Board for the Shandong Intervention Trial, which focused on delaying progression of precancerous gastric lesions. Dr. Yu’s expertise and dedication were crucial to ensuring that these studies were conducted according to the highest standards.

To bring leaders in the field of cancer epidemiology and genetics to NCI to share their expertise with scientific staff, DCEG created the Visiting Scholars Program (VSP), which was launched this spring. The program is structured around intensive two-day visits by world-class scientists from the extramural community and includes a special Scholar Seminar and round-robin visits with DCEG programs and branches. In addition to stimulating new ideas and research directions, the VSP will also focus on career development for young investigators in keeping with the priority that DCEG and NCI give to highquality research training. Program goals include fostering and reinforcing creative research approaches that enhance the intramural and collaborative research portfolio of DCEG and contribute to NCI and NIH strategic priorities.

“We are pleased to honor these scientists for their accomplishments in epidemiology and public health. Their visits also expose our scientific staff to cutting-edge research that is taking place outside NIH,” said DCEG Director Joseph F. Fraumeni, Jr., M.D.

The program was inaugurated March 17 with the visit of Dr. Elio Riboli, Chief of the Unit of Nutrition and Cancer at the International Agency for Research on Cancer in Lyon, France. During his seminar, “A multifactorial approach to cancer etiology,” Dr. Riboli discussed several global issues in the field of cancer epidemiology, including recent analyses from the European Prospective Investigation into Cancer (EPIC) study. Thematic breakout sessions included a meeting with DCEG investigators to discuss the consortium approach to cancer epidemiology and an exposureassessment working group meeting with a nutrition focus. An openforum Meet-the-Scholar session explored new research directions, opportunities for collaborative work, and career development issues. Dr. Riboli also toured the NCI Core Genotyping Facility at the Advanced Technology Center.

"We are pleased to honor these scientists for their accomplishments in epidemiology and public health. Their visits also expose our scientific staff to cutting-edge research that is taking place outside NIH,” said DCEG Director Joseph F. Fraumeni, Jr., M.D."

On May 10 and 11, DCEG hosted Dr. Jonathan Samet, Chair of the Epidemiology Department at the Johns Hopkins Bloomberg School of Public Health. Dr. Samet spoke on “The challenge of epidemiologic research: Continued lessons from lung cancer.” Breakout sessions focused on lung cancer research initiatives involving DCEG and training programs in specialized areas of epidemiology. Dr. Samet lunched with fellows during a Meet-the-Scholar session, during which the conversation focused on postfellowship career opportunities, the changing face of epidemiology, including the emerging role of largescale studies and consortia, and the importance of grant-writing experience. A forum on “Epidemiology training in an era of subspecialization” dealt with additional potential training collaborations with Johns Hopkins and teaching opportunities. The visit culminated with the development of a Graduate Training Partnership memorandum of understanding between DCEG and the Johns Hopkins Department of Epidemiology.

—Demetrius Albanes, M.D.

More than 30 DCEG staff members received special recognition at the Division’s annual town meeting in April. During the open discussion period, DCEG Director Joseph F. Fraumeni, Jr., M.D., talked about the challenges and opportunities facing DCEG and NCI and noted that research across the Division is “humming” despite budgetary constraints. Dr. Fraumeni emphasized the central role played by DCEG in developing strategic partnerships through research consortia, along with the Visiting Scholars Program, which is stimulating new ideas. In discussing the “power to convene” at NIH, Dr. Fraumeni underscored the opportunity to bring together various groups to address scientific issues through workshops and multicenter evaluations.

Shelia Zahm, Sc.D., DCEG Deputy Director, served as emcee of the award ceremony, which began with the 2003 Combined Federal Campaign (CFC) award. Under the excellent leadership of DCEG Coordinator Elyse Wiszneauckas, Office of the Director (OD), the Division received its sixth CFC Presidential Award and met 143 percent of its dollar goal. Recognition also went to Branch key workers: Holly Brown, Biostatistics Branch (BB); Patricia Chandler, Office of Division Operations and Analysis (ODOA); Natacha Charles, Clinical Genetics Branch (CGB); Jennifer Connor, Hormonal and Reproductive Epidemiology Branch (HREB); Michelle Fitzpatrick, Administrative Resource Center (ARC); Julie Russell Grey, Viral Epidemiology Branch (VEB); Wen-Yi Huang, Ph.D., Occupational and Environmental Epidemiology Branch (OEEB); Ursula Leitzmann, M.A., Radiation Epidemiology Branch (REB); Sandy Rothschild, (OD); Tawanda Roy, Nutritional Epidemiology Branch (NEB); and Rashida Williams, Genetic Epidemiology Branch (GEB).

Three fellows received awards for Outstanding Research Paper, which recognizes publications by fellows during the past calendar year that demonstrated impact, innovation, and clarity of thought and language. Michael Hauptmann, Ph.D. (BB), was recognized for his paper, “Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries,” published in the Journal of the National Cancer Institute; Sam Mbulaiteye, M.D. (VEB), for his paper, “Human herpesvirus 8 infection and transfusion history in children with sickle-cell disease in Uganda,” also published in the Journal of the National Cancer Institute; and Ulrike Peters, Ph.D. (NEB), for her paper, “Dietary fiber and colorectal adenoma in a colorectal cancer early detection program,” published in Lancet. The staff scientist Outstanding Research Paper award went to Dr.Huang for her paper, “Alcohol concentration and risk of oral cancer,” published in the American Journal of Epidemiology.

Three postdoctoral fellows received the DCEG Fellowship Achievement Awards for outstanding productivity: Lifang Hou, M.D., Ph.D. (OEEB), Tania Mara Welzel, M.D., Ph.D. (VEB), and Rose Yang, Ph.D. (GEB). The winners receive a two-step annual increase in their NCI fellowship stipend.

This year, the Division selected four individuals to receive Special Recognition Awards. Betty Jane (B.J.) Stone, Ph.D. (BB), was honored for exemplary service and meticulous work as Chair of the Technical Evaluation of Questionnaires Committee. Nathaniel Rothman, M.D. (OEEB), and Jim Vaught, Ph.D. (OD), were recognized for organizing the DCEG Molecular Epidemiology Course, and Donna Gellerson (ARC) was honored for extraordinary work as manager of the DCEG Administrative Resource Center.

The Outstanding Mentor Award honors scientists who demonstrate exceptional skill in and commitment to training and mentoring. Mark H.Greene, M.D. (CGB), was recognized by fellows for being an “outstanding scientist, collaborator, and mentor” and for “encouraging creativity and innovation and serving as a role model for all young investigators.” Rashmi Sinha, Ph.D. (NEB), was also honored for her ability to “guide fellows through complex scientific issues and to ensure a productive and rewarding training experience.” Betsy Duane-Potocki (OD) was recognized for her work in mentoring a long line of communications interns. Under her guidance, interns “grow in their communications skills, in confidence, and in understanding of our research enterprise.”

Finally, Exemplary Service Awards went to Susan Devesa, Ph.D. (BB), and Neil Caporaso, M.D. (GEB), for their sustained research accomplishments and outstanding service to the Division. Dr. Devesa was cited for her pivotal role in analyzing and interpreting descriptive data on cancer incidence and mortality and in directing the development of the U.S. Atlas of Cancer Mortality. She is an invaluable consultant, collaborator, and mentor to scientists across the Division and NCI. Dr. Caporaso was cited for unselfish participation on numerous committees, including the DCEG Biorepository Review Group, the DCEG Molecular Epidemiology Committee, and several NCI committees and working groups addressing tobacco-related research. At the same time, he has conducted state-of-the-art research on geneenvironment interactions in lung cancer and has spearheaded creation of an international consortium of researchers involved in the study of familial chronic lymphocytic leukemia.

Congratulations to two DCEG fellows who recently received doctoral degrees. Preetha Rajaraman, Ph.D., of the Radiation Epidemiology Branch (REB), completed her doctoral degree through the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. Her dissertation research focused on occupational exposure to lead, genetic susceptibility, and risk of brain tumors in adults, and was completed under the mentorship of Peter Inskip, Sc.D. (REB), and Patricia Stewart, Ph.D., Occupational and Environmental Epidemiology Branch (OEEB). Dr. Jonathan Samet of Johns Hopkins was her faculty advisor.

Elizabeth Brown, Ph.D., of the Viral Epidemiology Branch (VEB), successfully defended her doctoral thesis, which was also completed through the Department of Epidemiology at Johns Hopkins. Her dissertation research, “Human herpesvirus-8 and classical Kaposi sarcoma in an Italian case-control study,” focused on phenotypic and genotypic markers of immunity. James Goedert, M.D. (VEB), Stephen Chanock, M.D., of NCI’s Core Genotyping Facility, and Dr. Anthony Alberg of Johns Hopkins were her mentors.

Drs. Brown and Rajaraman will continue to work in DCEG as postdoctoral fellows. In addition to graduation ceremonies at Johns Hopkins, they also participated in the annual Certificate Award Ceremony for graduate students at NIH and in the first NIH Graduate Student Symposium Day. Dr. Rajaraman was one of nine NIH graduate students selected to give an oral presentation on her dissertation research project, and Dr. Brown gave a poster presentation.

Other DCEG graduate students who gave poster presentations at the symposium included Sadie Hutson, Ph.D., C.R.N.P. (Clinical Genetics Branch), on “The experiences of siblings of patients with Fanconi’s anemia,” and Hormuzd Katki, M.S. (Biostatistics Branch), on “Extending Mendelian mutation prediction models to handle errors in reported family history.”

Graduate students from more than 50 universities who were completing doctoral research at NIH took part in the symposium. The daylong event also featured distinguished speakers, including Dr. Harold Varmus, NIH director from 1993 to 1999 and currently president of Memorial Sloan-Kettering Cancer Center in New York. In addition to showcasing graduate student research at NIH, outstanding mentors were honored.

People come from all over the world to work in DCEG, NCI, and NIH. The gathering of individuals from diverse places and backgrounds creates a rich intellectual environment but can also cause communication problems due to cultural differences that lead to misunderstandings. Key stumbling blocks in communication across cultures include language differences, assumptions of similarities, and nonverbal patterns. Intercultural communication skills can help people better understand those who think and behave differently through reconciling conflicting values to create shared meaning.

To build and sustain an effective and successful work environment, DCEG offers a series of Cultural Considerations Workshops. Initially targeted at DCEG international fellows, the workshops have been made available to other DCEG staff and fellows in NCI’s Center for Cancer Research. Led by intercultural trainer Ursula Leitzmann, M.A., of the Radiation Epidemiology Branch, the workshops introduce individuals to the concepts of cultural awareness and communication. Attendees learn to understand the visible aspects of culture, such as behavior, and underlying beliefs and values—the less visible aspects of culture. Special attention is given to American cultural values, such as the preference for task orientation and individual achievement. In the workshops, intercultural skills are strengthened through a series of case studies.

I-131 COMMUNICATIONS AID WINS PLAIN LANGUAGE AWARD

Betsy Duane-Potocki (Office of the Director) and Andre Bouville, Ph.D. (Radiation Epidemiology Branch), were part of a group of collaborators who received an NIH Plain Language Award in May. The group won for its work on a flip chart that is part of a series of communications materials developed to provide information for Americans exposed to I-131 (a form of radioactive iodine) through fallout from aboveground nuclear testing in the 1950’s and early 1960’s. The flip chart, which received an award in the “Outstanding” category, targets Native Americans and is designed to help community leaders and healthcare professionals address concerns about I-131 exposure and thyroid cancer. Margaret Farrell, M.P.H., R.D., in the NCI Office of Communications, led the project. More information about the NIH I-131 communications materials can be found at http://cancer.gov/i131.

NIH launched the Plain Language Initiative in 1999, following a White House memorandum calling for clearer writing throughout the Federal government. Plain language documents should have logical organization and easy-to-read design features and use personal pronouns, short sentences, and common, everyday words.

Two DCEG scientists have been selected to receive the 2004 Department of Health and Human Services (DHHS) Secretary’s Award for Distinguished Service. Robert Hoover, M.D., Sc.D., and Shelia Zahm, Sc.D., were the only two NCI nominees chosen by DHHS Secretary Tommy Thompson for this honor. Individuals are selected for outstanding abilities, leadership skills, and exceptional contributions to the Department’s mission. Secretary Thompson will present the awards on July 14.

"Two DCEG scientists have been selected to receive the 2004 Department of Health and Human Services (DHHS) Secretary’s Award for Distinguished Service. Robert Hoover, M.D., Sc.D., and Shelia Zahm, Sc.D., were the only two NCI nominees chosen by DHHS Secretary Tommy Thompson for this honor."

Dr. Hoover, who directs DCEG’s Epidemiology and Biostatistics Program, was cited for pioneering research in identifying environmental and genetic determinants of cancer and for his enduring contributions to epidemiology and public health. His personal research on hormones and cancer included the first study linking hormone replacement therapy to breast cancer and the most comprehensive study of women exposed to diethylstilbestrol and their children. He has also directed a wide-ranging multidisciplinary epidemiology program covering virtually every cancer and risk factor. Widely recognized as one of the nation’s leading cancer epidemiologists, Dr. Hoover is an outstanding methodologist and a major force behind the recently created NCI Consortium of Cohorts, which will help clarify the role of environmental and genetic factors and their interactions in cancer etiology.

Dr. Zahm, who is Deputy Director of DCEG, was cited for her leadership and coordination of national research programs in environmental and occupational cancers, including major initiatives to evaluate the relationship of exposures to cancer and to investigate the risk of occupational cancer among women. She has played a key role in sustaining and strengthening a highly collaborative program of epidemiologic and interdisciplinary research into the environmental and genetic determinants of cancer. In addition to her crucial role in helping shape and manage the Division’s research programs, Dr. Zahm has devoted a significant amount of time to a wide variety of scientific management responsibilities, such as chairing the panel to oversee the Chornobyl Research Program upon its transfer to DCEG.

Two high school students who participated in DCEG’s 2003 summer research program were recently selected to receive a Young Epidemiology Scholar (YES) award sponsored by the Robert Wood Johnson Foundation and the College Board. Chuankai Michael Pan, a senior at Winston Churchill High School in Potomac,MD, was selected as a regional finalist for his work on “Smoking and passive smoking in relation to gallstone disease among women in Shanghai, China.” Mr. Pan’s mentors were Wong-Ho Chow, Ph.D., and Bu-Tian Ji, M.D., Dr.P.H., of the Occupational and Environmental Epidemiology Branch. Mr. Pan will soon return to DCEG for a summer internship to continue his analysis of gallstone disease and smoking. In the fall he will attend the University of Pennsylvania.

Tian Yang, a senior from Montgomery Blair High School in Silver Spring,MD, was also selected as a regional finalist. Mr. Yang worked in the Viral Epidemiology Branch under the guidance of James Goedert, M.D. His project examined the effects of acetaminophen and nonsteroidal anti-inflammatory drug use among hemophiliacs. In the fall, Mr. Yang will attend Carnegie Mellon University in Pittsburgh.

The Robert Wood Johnson Foundation and the College Board sponsor the YES competition to inspire talented high school students to investigate the many behavioral, biological, environmental, and social factors that affect health, and to identify ways to improve public health. The competition offers college scholarship awards to high school juniors and seniors who conduct outstanding research projects that apply epidemiologic methods of analysis to a health-related issue.

"The Robert Wood Johnson Foundation and the College Board sponsor the YES competition to inspire talented high school students to investigate the many behavioral, biological, environmental, and social factors that affect health, and to identify ways to improve public health."

Every year, DCEG offers a summer research experience for students interested in exploring careers in cancer epidemiology, genetics, and related areas. It is open to high school, college, and graduate students, including medical and dental students. Successful applicants join the Division for at least eight weeks between May and September. Under the supervision of Division scientists, the students carry out epidemiologic projects. They are also encouraged to attend lectures offered under the NIH Summer Seminar Series, participate in DCEG seminars and meetings, and present their work at the NIH Summer Research Program Poster Day. More information on DCEG’s summer program.

MICHAEL KASTAN FINISHES BOARD TERM

In June 2004, Michael Kastan, M.D., Ph.D., completed five years of service as a member of the Clinical Sciences and Epidemiology Subcommittee of NCI’s Board of Scientific Counselors (BSC-1). Dr. Kastan, who is a professor and chairman of the Department of Hematology and Oncology at St. Jude’s Children’s Hospital in Memphis, TN, has served as chair of the BSC-1 since 2001. The BSC advises the Intramural Division Directors, along with the NCI Director and Deputy Directors, on matters concerning scientific program policy and future research directions, and evaluates the scientific productivity of the Intramural Research Program through the site visit process. As part of his BSC activities, Dr. Kastan also served on the Planning Committee for developing the FY 2003 Bypass Budget. His contributions to the Institute and to DCEG have been greatly appreciated.

Philip Castle, Ph.D., M.P.H., thought he was just fulfilling a degree requirementwhen he signed up for a physiology course while in graduate school at Johns Hopkins University. The course was a turning point, however.

“The class was incredible and very diverse…and I knew I wanted to do a lab rotation with the professor,” says Dr. Castle. “His lab was studying new methods of preventing sexually transmitted diseases. That was where and when I caught my public health bug.”

Before that, Dr. Castle, a native of Maine, was “more of a biologist but taking as much physics as I could because I felt I needed to understand it to be a good scientist.”He doesn’t see any of his education going to waste. “Every [experience], plus what I’ll learn in the future, is a tool to be applied to the problem. None of it goes away, and the key is to bring it all to the table until the problem is solved.”

The problem in question is preventing cervical cancer. Today, Dr. Castle—who was recently appointed as a tenure-track investigator in DCEG’s Hormonal and Reproductive Epidemiology Branch—is focused on the epidemiology, prevention, and treatment of human papillomavirus (HPV) infection, the causative agent of cervical cancer. Most women are infected with HPV at some point in their lives; usually, the infection clears without incident. Rarely, the virus persists, predisposing the woman to cervical cancer. The American Cancer Society estimated that in 2003, 12,200 women in the United States were diagnosed with this type of cancer, and 4,100 died as a result. Worldwide, cervical cancer has a large impact, accounting for nearly 500,000 new cases and nearly 250,000 deaths annually.

"I like the fact that we’re on the road to making a major public health impact on a worldwide cancer problem, particularly one that disproportionately affects developing countries. We have an opportunity that is very exciting— to take it [the cervical cancer field] to the next level and apply our knowledge from etiologic studies to make a difference."

After finishing his doctoral degree in biophysics, Dr. Castle joined NIH as a postdoctoral fellow at the National Institute of Diabetes and Digestive and Kidney Diseases to work on the molecular biology of the zona pellucida, the glycoprotein matrix that surrounds the mammalian egg and mediates early fertilization events. But his desire to be more immersed in etiology and public health led him to enter the NCI’s Cancer Prevention Fellowship program, run by the Division of Cancer Prevention. As part of the program, Dr. Castle completed an M.P.H. degree at the Johns Hopkins Bloomberg School of Public Health. He also began working with DCEG researchers Mark Schiffman, M.D., and Allan Hildesheim, Ph.D., on the molecular epidemiology of HPV and cervical cancer.

“I like the molecular epidemiology perspective,” the 39-year-old says. “I like the fact that we’re on the road to making a major public health impact on a worldwide cancer problem, particularly one that disproportionately affects developing countries. Some might say that the HPV and cervical cancer field is very mature with not much more to do, but actually there is still plenty to learn.We have an opportunity that is very exciting—to take it to the next level and apply our knowledge from etiologic studies to make a difference.”

Dr. Castle is working in three areas:

1. Natural history of infection.

   “In these studies, I’m trying to understand the interaction of the virus with the host, down to which cells are responsible for clearance of the infection,” he says. Questions to be answered include:

   • Can we measure immune responses from cervical secretions and get a whole profile of immune response?
   • Which molecular factors determine whether a woman clears the infection versus the unusual event where the infection progresses to precancer or cancer?
   • How do smoking and other sexually transmitted diseases other than HPV affect the risk of an increased risk of developing precancer in HPVinfected patients?

2. Evaluating methods for measuring HPV.

   “Because HPV is the central cause of cervical cancer, persistent viral infection must precede getting cancer,” adds Dr. Castle. “Being able to measure HPV and figure out the determinants of persistent infection—understanding this and validating the measurements—is an important part of what I do.” Dr. Castle also notes that further understanding etiologic intricacies in the HPV/cervical neoplasia relationship will help refine screening and diagnostic tools and advance the fields of prevention, diagnosis, and treatment.

3. Developing interventions that target women with persistent infection.

   “The obvious and most interesting tools are vaccines,” he says. “I’m involved in a number of activities to evaluate the mechanisms by which vaccines might prevent infection or lead to clearance of a pre-existing infection. What happens in the genital tract when a woman is vaccinated? Is it possible to measure antibodies? Does the menstrual cycle affect antibody levels and other markers of response? What are the critical biomarkers for clearance of infection?”

   According to Dr. Castle, “These three areas are so interrelated that one can’t be done without the others. Eventually, we will have the tools to prevent a major form of cancer.Why not shoot for that as a career goal? It’s better to swing for the fences than not to swing at all.”

-Nancy Volkers

DEBRA SILVERMAN IS NEW WOMEN SCIENTIST ADVISOR-ELECT

Debra Silverman, Sc.D., of the Occupational and Environmental Epidemiology Branch has been selected as the DCEG Women Scientist Advisor (WSA)-Elect. The WSA term is four years: two as WSA-Elect and two as the main representative. Dr. Silverman will work with Lynn Goldin, Ph.D., of the Genetic Epidemiology Branch, who is the current WSA for DCEG. Many thanks go to Rashmi Sinha, Ph.D., of the Nutritional Epidemiology Branch, who just finished serving as the WSA.

"The NIH WSA committee is composed of more than 30 women who are principal investigators across the NIH institutes. Member responsibilities include communicating about issues with women scientists, attending NIH-wide WSA meetings, and serving on tenure-track search committees."

The NIH WSA committee is composed of more than 30 women who are principal investigators across the NIH institutes. Member responsibilities include communicating about issues with women scientists, attending NIH wide WSA meetings, and serving on tenure-track search committees. Within DCEG, WSA advisors meet regularly with Division Director Joseph F. Fraumeni, Jr., M.D., to advise him on issues relevant to women scientists. The WSAs also participate in all DCEG Senior Advisory Group meetings. Within NCI, the WSAs choose a recipient for the annual Rosalind Franklin Award given at the NCI Combined Intramural Retreat and review applications for the Sallie Rosen Kaplan Fellowship, a competitive postdoctoral position for women in cancer research. The WSAs are conducting an NCI salary analysis to determine if gender inequities exist.

BREAST CANCER

Familial Breast Cancer Risk and Polymorphisms in DNA repair and BRCA1 -related Genes (full text)
Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Nineteen single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFss1, IGFBP3) were evaluated. Using the kin-cohort method, breast cancer risk for ages 50 and 70 was estimated from family cancer history data collected from a series of breast cancer cases (n = 748) identified in a cohort of female U.S. radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Genotypes associated with increased risk were XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; CI = 1.3–3.8), XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9), and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3). The risks for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. Some variants in genes within DNA repair pathways and BRCA1 interacting proteins may play a role as lowpenetrance breast cancer risk alleles. (Sigurdson AJ, Hauptmann M, Chatterjee N, Alexander BH, Doody MM, Rutter JL, Struewing JP. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes. BMC Cancer 2004;4:9)

CERVICAL CANCER

COLORECTAL CANCER

ENDOMETRIAL CANCER

ESOPHAGEAL CANCER

GENETICS

(full text) Using DNA from the SNP500Cancer Database, various ethnic populations were analyzed at 1,442 SNP loci to estimate gene heterozygosity. Analyses revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. These data suggest that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity, even in a sample of modest size, can help guide the search for diseaseassociated genes. (Hughes AL, Packer B, Welch R, Bergen AW, Chanock SJ, Yeager M. Widespread purifying selection at polymorphic sites in human protein-coding loci. Proc Natl Acad Sci 2003;100:15754-7)

Risks of Adverse Events in Patients with Fanconi Anemia (full text)
Fanconi anemia (FA) is an autosomal recessive condition associated with bone marrow failure (BMF) leading to acute myeloid leukemia (AML), solid tumors (ST), death, or necessitating hematopoietic stem cell transplant. Among a cohort of 144 patients with FA, individualized risks of each outcome were calculated, given the presence or absence of congenital abnormalities that occur frequently in FA. Abnormal radii were significant risk factors for BMF. The cumulative incidence of BMF by age 10 varied from 18 percent in the lowest BMF risk group to 83 percent in the highest. Patients in the lowest BMF risk group were most likely to live long enough to develop AML or ST, and (conversely) patients in the highest BMF risk group were least likely to live long enough to develop AML or ST. By age 40, the cumulative incidence of ST ranged from 0.6 percent to 29 percent in the highest and lowest BMF risk groups, respectively. Abnormal radii are the strongest predictor of early BMF in FA; a congenital abnormality score separates the large majority of FA patients with normal radii into distinct prognostic groups. (Rosenberg PS, Huang Y, Alter BP. Individualized risks of first adverse events in patients with Fanconi anemia. Blood 2004; Apr 1 [Epub ahead of print])

LUNG CANCER

LYMPHOHEMATOPOIETIC CANCER

Risk of Lymphoproliferative Tumors among Families with CLL
The spectrum of malignancies that share common genetic factors with chronic lymphocytic leukemia (CLL) and the effects of gender and age on familial risk are unknown. The Swedish Family Cancer Database was used to test for increased familial risks of CLL and other lymphoproliferative tumors. Cancer diagnoses from 1958 to 1998 were assessed in 14,336 first-degree relatives of 5,918 CLL cases and in 28,876 first-degree relatives of 11,778 controls. Relatives of cases were at significantly increased risk for CLL (relative risk [RR] = 7.52; CI = 3.63–15.56), for non- Hodgkin’s lymphoma (RR = 1.45; CI = 0.98–2.16) and for Hodgkin’s lymphoma (RR = 2.35; CI = 1.08–5.08). CLL risks were similar in parents, siblings, and offspring of cases, in male and female relatives, and were not affected by the cases’ age at diagnosis. Anticipation was not significant. The familial component for CLL is shared with other lymphoproliferative malignancies, suggesting common genetic pathways. (Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: Results from the Swedish Family-Cancer Database. Blood 2004; May 25 [Epub ahead of print])

Hepatitis C Virus and Non-Hodgkin’s Lymphoma (full text)
To further investigate the suspected link between hepatitis C virus (HCV) infection and non-Hodgkin’s lymphoma (NHL), testing was done on serum samples from 998 women (464 NHL cases; 534 controls) from Connecticut. Approximately 2 percent of cases and 1 percent of controls tested positive for HCV. The risk of NHL associated with HCV infection appeared to be concentrated among B-cell lymphomas (B-NHL) (OR = 2.0; CI = 0.6–8.2), particularly follicular lymphoma (OR = 4.1; CI = 0.8–19.4). Although the low prevalence of HCV in this population resulted in wide CIs for the estimated association between HCV and B-NHL subtypes, this study suggests that HCV may be associated with an increased risk of B-NHL, and that this risk may vary by B-NHL subtype. (Morton LM, Engels EA, Holford TR, Leaderer B, Zhang Y, Zahm SH, Boyle P, Zhang B, Flynn S, Tallini G, Owens PH, Zheng T. Hepatitis C virus and risk of non-Hodgkin lymphoma: A population-based casecontrol study among Connecticut women. Cancer Epidemiol Biomarkers Prev 2004;13:425-30)

METHODS

Risk of Human Herpesvirus-8 Infection from Transfusions (full text)
In studies of infectious disease, epidemiologists frequently estimate and compare incidence rates among different age groups, and inferences are based on cross-sectional rather than prospective data, often consisting of age at the time of study, infection status, and a chronology of events possibly associated with the disease. To understand how human herpesvirus 8 (HHV-8) is transmitted among children with sickle cell anemia in Uganda, a flexible parametric approach was developed for combining current-status data with a history of blood transfusions. Heterogeneity in transfusion-associated risk by childspecific random effects, such as host response to infection, was also modeled. An extension of the model was developed to account for the fact that the antibody assay used to detect HHV-8 status has imperfect sensitivity and specificity. These models allow the incorporation of maximum amounts of data and may improve efficiency of risk estimates. (Pfeiffer RM, Mbulaiteye S, Engels E. A model to estimate risk of infection with human herpesvirus 8 associated with transfusion from cross-sectional data. Biometrics 2004;60:249-56)

Loss of Antigenicity in Tissue Microarrays (full text)
The recent development of the tissue microarray (TMA) technique allows for standardized, rapid, and cost-effective immunohistochemical characterization of many cases of breast cancer and can be used to identify subtypes with distinct etiology. To evaluate whether staining intensity declines in whole sections prepared from conventional paraffin blocks with storage time (resulting in falsenegative results), a single TMA block from 125 invasive breast carcinomas was analyzed. Estrogen receptor (ER)-alpha, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in sections cut and stored for six months at room temperature were compared with sections cut from the same TMA block and stained on the same day. Percentage of positive cases for stored versus fresh sections was similar for ER (59 percent) but significantly higher in fresh sections for PR (56 versus 64 percent, p = 0.01) and HER2 (46 percent versus 64 percent, p < 0.001). Among cases positive in both stored and fresh sections, the median percentage of immunoreactive cells was significantly reduced and the staining intensity was consistently lower in stored compared with fresh sections. Loss of immunoreactivity is an important problem in TMAs of breast cancer. (Fergenbaum JH, Garcia-Closas M, Hewitt SM, Lissowska J, Sakoda LC, Sherman ME. Loss of antigenicity in stored sections of breast cancer tissue microarrays. Cancer Epidemiol Biomarkers Prev 2004;13:667-72)

OBESITY

OVARIAN CANCER

Ovarian Cancer Risk After Use of Ovulation-Stimulating Drugs (full text)
A retrospective cohort study of 12,193 eligible study subjects (median age 30 years), who were evaluated for infertility during the period of 1965 to 1988 at five clinical sites, identified 45 subsequent ovarian cancers. The infertility patients had a significantly elevated ovarian cancer risk compared with the general population (standardized incidence ratio = 1.98; CI = 1.4–2.6).When patient characteristics were taken into account and risks assessed in the infertile women, the rate ratios (RR) associated with ever use were 0.82 (CI = 0.4–1.5) for clomiphene and 1.09 (CI = 0.4–2.8) for gonadotropins. There were higher but nonsignificant risks with follow-up time. Although drug effects did not vary by causes of infertility, a slightly higher risk was associated with clomiphene use among women who remained nulligravid, based on six exposed patients (RR = 1.75; CI = 0.5–5.7). These results do not confirm the strong link reported in some studies between ovulationstimulating drugs and ovarian cancer. Slight but nonsignificant elevations in risk associated with drug use among certain subgroups of users, however, support the need for continued monitoring of long-term risks. (Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE,Westhoff CL. Ovarian cancer risk after the use of ovulation-stimulating drugs. Obstet Gynecol 2004;103:1194-1203)

PANCREATIC CANCER

Nitrates in Drinking Water and Pancreatic Cancer (full text)
N-nitroso compounds, which are known animal carcinogens, are formed endogenously from intake of nitrate and nitrite. A population-based study of 189 pancreatic cancer cases and 1,244 controls in Iowa was conducted to determine whether increased consumption of nitrate and nitrite from drinking water and dietary sources was associated with risk. No association was observed between pancreatic cancer risk and increasing quartiles of nitrate in community water supplies. Increasing intake of dietary nitrite from animal sources, however, was associated with significantly elevated risks among men (highest quartile OR = 2.3, CI = 1.1–5.1) and women (OR = 3.2, CI = 1.6–6.4). In contrast, dietary nitrate intake showed no positive association with risk among men or women. Thus, long-term exposure to drinking-water nitrate at levels below the maximum contaminant level of nitrate nitrogen (10 mg/liter) is not associated with pancreatic cancer, but the consumption of dietary nitrite from animal products may increase risk. (Coss A, Cantor KP, Reif JS, Lynch CF,Ward MH. Pancreatic cancer and drinking water and dietary sources of nitrate and nitrite. Am J Epidemiol 2004;159:693-701)

PEDIATRIC CANCER

RADIATION

Dalsu Baris, M.D., Ph.D., of the Occupational and Environmental Epidemiology Branch (OEEB), was invited to serve on the Scientific Board of Advisors to the International Myeloma Foundation (IMF) for the Bank on a Cure Project. IMF is a nonprofit organization dedicated to improving the lives of multiple myeloma patients. The Bank on a Cure Project will establish a comprehensive DNA repository from myeloma patients for epidemiologic and clinical research (http://myeloma.org/myeloma/home.jsp). Dr. Baris made a presentation on molecular epidemiology and multiple myeloma at the board’s recent meeting in Bermuda.

Sonja Berndt, Pharm.D., a predoctoral fellow in OEEB, received the Louis I. and Thomas D. Dublin Award in Epidemiology and Biostatistics from Johns Hopkins University for her proposal, “A comparison of approaches for estimating haplotype-disease associations.”

Louise Brinton, Ph.D., Hormonal and Reproductive Epidemiology Branch (HREB), spoke on “Interpreting epidemiologic findings: Hormones and cancer risk,” at the 5th International Symposium on Women’s Health and Menopause, held in Florence, Italy, in April, and on “Cancer risk associated with causes of and treatments for infertility” at the Danish Cancer Registry in Copenhagen, also in April.

Melinda Butsch Kovacic, Ph.D. (HREB), has been selected as the editor for POSTDOCket, the quarterly newsletter for the National Postdoctoral Association (http://www.nationalpostdoc.org).

Kenneth Cantor, Ph.D. (OEEB), gave an invited talk on “Ingested arsenic and cancer epidemiology” at the American Association for the Advancement of Science meeting in Seattle in February.

Philip Castle, Ph.D. (HREB), spoke on “Human papillomavirus (HPV) and cervical cancer” at the University of Hawaii School of Medicine, and on “Practical applications concerning HPV carcinogenesis in screening and development: Vaccine development” at the International Association of Dental Research meeting in Honolulu in March.

Shih-Chen Chang, Ph.D., Nutritional Epidemiology Branch (NEB), received an American Society of Preventive Oncology (ASPO) new investigator award for his abstract on “Association of dietary fat and colorectal adenoma.”Dr. Chang presented this research and “Interrelation of energy intake, body size, and physical activity with postmenopausal breast cancer in the PLCO Screening Trial” at the ASPO meeting in Bethesda in March.

Eric Engels, M.D., Viral Epidemiology Branch (VEB), spoke on “Polyomavirus and childhood cancer” at the Children’s Oncology Group meeting in Washington, DC, in April.

Mary Fraser, R.N., M.A., Genetic Epidemiology Branch (GEB), gave an invited presentation on “Education through publication” at the Dermatology Nurses’ Association 2004 Skin Cancer Workshop in Orlando in March. Ms. Fraser also was appointed to the Dermatology Nursing editorial board.

Mitchell Gail, M.D., Ph.D., Biostatistics Branch (BB), spoke on “Preparing statisticians for research at the National Institutes of Health” at the Eastern North American Regional meeting of the American Statistical Society in Pittsburgh in March.

Jim Vaught, Ph.D. (Office of the Director), gave the keynote address at the U.S. meeting of the International Society for Biological and Environmental Repositories in New York City in May. He spoke on “Large biorepositories: Are there smarter ways to collect and store specimens?” Dr.Vaught also was selected to receive the 2004 Distinguished Alumnus Award from the School of Graduate Studies at the Medical College of Georgia, where he completed a Ph.D. in biochemistry in 1976. Jim Vaught receives 2004 Distinguished Alumnus Award from Elizabeth Leibach, President of the Medical College of Georgia School of Graduate Studies Alumni Association Shih-Chen Chang

Michael Hauptmann, Ph.D. (BB), gave talks on cancer and formaldehyde at the Toxicology Forum Winter Meeting in Washington, DC, in February, and at the Department of Environmental and Occupational Health Sciences, University of Washington, in Seattle in April. Dr. Hauptmann also spoke on “Gene-environment interactions in case-control designs,” at the Department of Epidemiology and Preventive Medicine at the University of Maryland in Baltimore in February.

Sadie Hutson, Ph.D., C.R.N.P., Clinical Genetics Branch (CGB), was selected to receive the Virginia Henderson Clinical Research Grant from Sigma Theta Tau International (the Honor Society of Nursing). The award is given to one recipient each year and helps fund study-related expenses.

Ruth A. Kleinerman, M.P.H. (REB), gave an invited lecture on “Second cancer risk following radiotherapy” at the Radiation Research Society meeting in St. Louis,MO, in April.

Qing Lan, M.D., Ph.D. (OEEB), and Neil Caporaso, M.D. (GEB), participated in the first meeting to form an international lung cancer consortium, which took place at the American Association for Cancer Research (AACR) meeting in Orlando in March. Dr. Lan presented a history of DCEG studies in Xuan Wei, China, that identified the study of the molecular epidemiology of lung cancer in nonsmoking women as one of the highestpriority research areas.

Michael Leitzmann, M.D., Dr. P.H. (NEB), gave invited presentations in January on “Diet and lifestyle factors in relation to prostate cancer risk” at the International Agency for Research on Cancer in Lyon, France, and at the German National Cancer Institute in Heidelberg.

Unhee Lim, Ph.D. (NEB), was invited to speak at the ASPO New Investigators workshop in Bethesda in March. Dr. Lim talked on “A biomarker study of onecarbon metabolism and colorectal adenoma in the CONCeRN (Colorectal Neoplasia Screening with Colonoscopy in Asymptomatic Women at Regional Navy/Army Medical Centers) Study.” She gave a second oral presentation at ASPO on “Dietary B vitamins and the risk of lymphoid cancers in male smokers.”

Roxana Moslehi, Ph.D. (BB), gave an invited presentation on cancer and developmental issues in the xeroderma pigmentosum heterozygote study at the American Academy of Dermatology meeting in Washington, DC, in February. Dr.Moslehi also spoke on “Cancer risks associated with DNA repair genes” at the Johns Hopkins Bloomberg School of Public Health, also in February.

Thomas O’Brien, M.D. (HREB), gave a lecture on “Genomics and proteomics: Promises and pitfalls” at the 35th Anniversary Meeting of the Southeastern Organ Procurement Foundation in Richmond in March. Dr. O’Brien moderated the session on “Pathogenesis” at a meeting on hepatocellular carcinoma at NIH in April.

June Peters, M.S., C.G.C. (CGB), coauthored “Genetic cancer risk assessment and counseling: Recommendations of the National Society of Genetic Counselors (NSGC),” which appeared in the April 2004 issue of Journal of Genetic Counseling. This is the first set of guidelines on cancer risk produced by the NSGC (http://www.nsgc.org/).

Margaret Tucker, M.D. (GEB), gave an “Overview of genetic epidemiology” at the first NCI–King Hussein Cancer Center Conference and the 4th Jordan Oncology Society Conference, which were held in Amman, Jordan, in April. She also gave two talks at St. James Hospital in Dublin, Ireland, in March on “Challenges and opportunities in genetic epidemiology” and “Genetic epidemiology of melanoma.” In addition, Dr. Tucker was inducted into the American Epidemiological Society in March.

 

 

Charles Rabkin, M.D. (VEB), gave an invited talk on “The molecular epidemiology of Kaposi’s sarcoma and other AIDS-related malignancies” to the Uganda Society of Health Scientists in March. Dr. Rabkin and Sam Mbulaiteye, M.D. (VEB), also participated in the Annual Conference of Physicians of Uganda.

Preetha Rajaraman, Ph.D. (REB), was inducted into Delta Omega, a national honorary society for graduate students in public health, in May.

Tanuja Rastogi, Sc.D. (NEB), gave an oral presentation on “Diet and risk of biliary tract cancers: A population-based study in Shanghai, China,” at the ASPO meeting held in Bethesda in March. This paper was selected as one of the top meeting abstracts.

Cecile Ronckers, Ph.D. (REB), received the Brigid G. Leventhal Scholar Award in Cancer Research from the AACR Women in Cancer Research group in Orlando in April for her work on “Second primary thyroid cancer after a first childhood malignancy.” Dr. Ronckers also delivered a lecture on “Radiation and cancer” at the University of Maryland in April.

Nathaniel Rothman, M.D. (OEEB), chaired a meeting of the Genetic Polymorphism Working Group of InterLymph, an international consortium of non-Hodgkin’s lymphoma (NHL) studies, held at the AACR meeting in Orlando in March. At the meeting, Sophia Wang, Ph.D. (HREB), and Qing Lan, presented preliminary results from a meta-analysis of single nucleotide polymorphisms from eight NHL case-control studies. This represents one of the first consortia efforts to study common genetic variants and cancer risk.

Arthur Schatzkin, M.D., Dr.P.H. (NEB), spoke on “Problems with using biomarkers as surrogate end points for cancer” at the Controversies in Tumor Prevention and Genetics conference in St. Gallen, Switzerland, in February. Dr. Schatzkin also gave presentations on nutrition and cancer at the American Epidemiological Society meeting in Seattle in March, and at the Albert Einstein College of Medicine, New York, in April.

Lois Travis, M.D., Sc.D. (REB), served on the faculty for an American Society of Clinical Oncology’s educational symposium called “The Price of Success: Long-term Complications of Treatment,” during the annual meeting in New Orleans in June. Dr. Travis also gave an invited talk on “Second cancers: An overview” for Grand Rounds at the Memorial Sloan-Kettering Cancer Center in New York in April.

Gloria Gridley, M.S., and B.J. Stone, Ph.D. (BB), led a session at the NIH Take Our Sons and Daughters to Work Day in April. Under their guidance, students surfed the NCI Cancer Atlas web site and viewed U.S. cancer mortality maps. Students were taught how epidemiologists use these maps to search for clues to cancer etiology.

Roel Vermeulen, Ph.D. (OEEB), gave a talk on “Exposure assessment: Dealing with variability” at the University at Albany School of Public Health, Department of Epidemiology, in April.

Mary Ward, Ph.D. (OEEB), addressed the Texas School of Rural Public Health in Bryan, TX, on “Using GIS for exposure assessment of pesticides in drinking water” in April.

Robin Wilson, Ph.D. (OEEB), spoke on “The role of primary care patterns in stage at diagnosis outcomes among American Indian cancer patients” at the Pennsylvania State College of Medicine in Hershey in March.

Margaret Wright, Ph.D. (NEB), received a New Investigators Award and gave a presentation on “Elucidating the biological effects of B-carotene supplementation on lung carcinogenesis in male smokers” at the ASPO meeting in Bethesda in March. Dr.Wright also presented on “Effect of estimated renal net acid excretion on bladder cancer risk” at the Experimental Biology Annual Meeting in Washington, DC, in April.

INNOVATIVE PROPOSALS WIN INTRAMURAL RESEARCH AWARD

DCEG funds several Intramural Research Awards (IRAs) each year that recognize small, innovative, and interdisciplinary research projects. This year’s winners are Eric Engels, M.D., M.P.H., of the Viral Epidemiology Branch; Montserrat Garcia-Closas, M.D., Dr.P.H., of the Hormonal and Reproductive Epidemiology Branch; and Rachel Stolzenberg-Solomon, Ph.D., M.P.H., of the Nutritional Epidemiology Branch. All are DCEG tenure-track investigators.

Dr. Engels won for his proposal to investigate BK virus (BKV) in neuroblastoma. Neuroblastoma is the most common malignancy in infants. The etiology is unknown, but a recent study suggested that early-life infection with the BK polyomavirus might be a factor. Dr. Engels and his collaborators will seek to determine whether BKV can be detected in neuroblastoma tissue and to identify whether in utero or early-life transmission occurs in children who subsequently develop these tumors.

Dr. Garcia-Closas was recognized for her proposal to validate the use of pooled DNA to identify associations between genetic polymorphisms and bladder cancer risk. Using pooled DNA samples from many individuals rather than individual samples to obtain estimates of allele frequencies (allelotyping) is a promising approach to efficiently screening large numbers of single nucleotide polymorphisms (SNPs) for their association with cancer risk. Using samples from a study of bladder cancer, Dr. Garcia-Closas will develop and validate 500 allelotyping assays at the NCI Core Genotyping Facility. This technology will then be applied to screen for potentially relevant SNPs in key pathways that may lead to bladder cancer.

Dr. Stolzenberg-Solomon won for her proposal to evaluate endogenous sex hormones in postmenopausal women during weight loss and weight loss maintenance. An estimated 25 percent of breast cancer cases may be attributable to obesity and sedentary lifestyle, putatively through mechanisms that alter endogenous hormones. This project will be ancillary to the extramural National Heart, Lung, and Blood Institute study, The Weight Loss Maintenance Trial.

In the IRA program, tenure-track investigators and fellows in the Division apply for funds (up to $75,000 per year, renewable for up to three years) for small projects that cross usual organizational boundaries. Each proposal is reviewed by a member of the NCI Board of Scientific Counselors or another scientist from outside NIH with appropriate expertise, plus senior DCEG scientists. The proposals are judged with respect to their potential for significant scientific or public health impact, innovative aspects of the approach or methodology, interdisciplinary and collaborative nature of the project, ability to achieve the objectives within the proposed time frame and resources, and programmatic relevance to the Division. The award can be combined with funds from other sources to support a larger project.

Michelle Althuis, Ph.D., a postdoctoral fellow in the Hormonal and Reproductive Epidemiology Branch (HREB) since 2001, has accepted an Assistant Professor position at Georgetown University Lombardi Comprehensive Cancer Center. While in DCEG, she studied exogenous exposures and hormone-related cancer etiology. She also evaluated cancer risk following ovulation-stimulating drug use and breast cancer risk associated with oral contraceptives.

Gabriella Andreotti, M.P.H., has joined HREB as a predoctoral fellow. Ms. Andreotti, a doctoral student at the George Washington University (GWU) School of Public Health, will conduct dissertation research on the role of genetic susceptibility in biliary tract cancer. Ms. Andreotti received an M.P.H. degree in epidemiology from GWU in 1998. Since then, she has carried out epidemiologic surveillance and research in the Army Medical Surveillance Program at the Walter Reed Army Medical Center.

Andrea Baccarelli, M.D., Ph.D., Genetic Epidemiology Branch (GEB), left DCEG in May. Dr. Baccarelli returned to Italy to accept an appointment as Assistant Professor in the Department of Occupational and Environmental Health at the University of Milan. He will work in the Research Center on Occupational, Environmental and Clinical Epidemiology and will focus on molecular epidemiology.

Kaye Brock, Ph.D., a senior lecturer in the School of Behavioral and Community Health Sciences at the University of Sydney in Australia, is spending a fivemonth sabbatical in the Biostatistics Branch (BB).

Sylvia Cameraro, M.Sc., an industrial hygienist from the University Institute of Oncologia of the Principality of Asturias in Spain, is visiting the Occupational and Environmental Epidemiology Branch (OEEB) for three months. She will assess chemical exposures identified in the Spanish Bladder Cancer Study.

Sophie Fossa, M.D., Ph.D., of the Norwegian Radium Hospital and the University of Oslo, is a Visiting Scientist in the Radiation Epidemiology Branch until August. As a clinical oncologist and radiotherapist, Dr. Fossa has a special interest in survivorship issues and is collaborating with Dr. Lois Travis and colleagues on international studies of second cancers and mortality among survivors of testicular cancer and Hodgkin’s lymphoma.

Carsten Hirt, M.D., has joined the Viral Epidemiology Branch as a visiting fellow. For his medical thesis, he conducted research on detecting minimal residual disease in low-grade non-Hodgkin’s lymphoma (NHL) by real-time quantitative polymerase chain reaction. Before coming to NCI, he was a clinical fellow in the Department of Hematology and Oncology at the University of Greifswald in Germany. Dr. Hirt will work on determining correlates and predictors of peripheral blood mononuclear cells bearing NHL-associated translocations, and the relationship of these mutations to the risk of NHL among subjects with advanced HIV infection and in the general population.

Kimberly Kerstann, Ph.D., has joined GEB as a postdoctoral fellow. Dr. Kerstann received a doctoral degree in genetics and molecular biology from Emory University in 2003. Before coming to DCEG, she was a postdoctoral fellow at the National Human Genome Research Institute, where she studied the variability of methylation patterns in the promoter region of cancer-associated genes. Dr. Kerstann will apply her experience in identifying susceptibility genes/risk factors in association studies to the field of cancer genetics. She is working on analyses of family history of cancer among relatives of glioma cases from the DCEG case-control study of brain tumors.

Larissa Korde, M.D., M.P.H., has joined the Epidemiology and Biostatistics Program as a Cancer Prevention fellow. Dr. Korde received a medical degree from New York Medical College and completed her internal medicine residency at Georgetown University. She is now finishing oncology subspecialty training at NCI and will work on analyses of soy intake during childhood, adolescence, and adult life. Dr. Korde is also working on clinical intervention trials to reduce breast cancer risk through physical activity at NCI’s Center for Cancer Research.

Srmena Krstev, M.D., Ph.D., has returned to the Institute of Occupational and Radiological Health in Belgrade, Yugoslavia, after completing a sabbatical year in OEEB.While in DCEG, Dr. Krstev evaluated occupational exposures associated with nonmalignant respiratory disease in the Shanghai Women’s Cohort. She also evaluated the mortality experience among a cohort of workers employed in the U.S. Coast Guard Shipyard in Baltimore.

Mark Purdue, Ph.D., has joined OEEB as a visiting fellow. Dr. Purdue recently completed a doctoral degree in epidemiology at the University of Toronto. His dissertation research examined risk factors for p53 protein abnormalities in malignant melanoma. During his fellowship, Dr. Purdue plans to study hormone replacement therapy and adenomatous polyps in the PLCO trial, and environmental tobacco smoke and colorectal cancer in the Shanghai Women’s Cohort.

Isela Velazquez, M.D., completed an M.P.H. fellowship in the Clinical Genetics Branch and has accepted a position as an Associate Medical Director with AstraZeneca in Wilmington, DE. During her DCEG fellowship, Dr.Velazquez worked on a prospective analysis of the penetrance of BRCA1 and BRCA2 mutations in hereditary breast/ovarian cancer. She also worked on the role of androgens in liver tumors among individuals with and without Fanconi’s anemia.

Ulrike Peters, Ph.D., a postdoctoral fellow in the Nutritional Epidemiology Branch, left DCEG in May to take a faculty position at the Fred Hutchinson Cancer Research Center at the University of Washington in Seattle. During her fellowship, Dr. Peters worked on molecular epidemiology studies of nutritional exposures in relation to colorectal and prostate cancer risk. She was involved with the Navy Colorectal Adenoma Study, the Beltsville Feeding Study, and the Swedish In-Patient Registry, and played a pivotal role in managing the etiologic component of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Trial.

BETH MALONEY JOINS CDC

Elizabeth (Beth) Maloney, Dr.P.H., who worked in the Viral Epidemiology Branch for 21 years, left DCEG in February to join the Centers for Disease Control and Prevention in Atlanta. Dr. Maloney started at NCI in 1983 as an epidemiology research assistant in what was then the Viral Epidemiology Section. With an undergraduate degree in psychology, she knew she wanted to pursue work in the public health field. That pursuit eventually led to an M.S. degree in biostatistics from Georgetown University and a doctoral degree in public health in 2001 from the Uniformed Services University of the Health Sciences.

“DCEG’s support of my education and training made my many years at NCI an ever-changing experience by providing new opportunities for professional growth,” said Dr. Maloney. “In particular, Dr. Bill Blattner took the first chance on me by bravely supporting my master’s degree, and Dr. Angela Manns and Dr. Jim Goedert gave me the time to complete coursework for my doctoral training. I am grateful not only for their selfless choices but also for their belief in me.”

Over the years, Dr. Maloney focused her research on the study of human T-cell lymphotrophic virus (HTLV). She was a lead investigator on the Jamaican Mother-Infant Cohort Study of HTLV-I and on the Study of HTLV-II in the Guaymi Amerindians of Panama. She and her Jamaican colleagues reported HTLV-I–associated conditions in children. Working with Dr. Ruthann Giusti and collaborators from Panama, she described sexual risk factors for HTLV-II infection in the Guaymi. Dr. Maloney also serves as an editorial reviewer for several journals, including the International Journal of Epidemiology and the Journal of Infectious Diseases.

Dr. Maloney now is an epidemiologist at the National Center for Infectious Diseases in the Division of Viral and Rickettsial Diseases. She works with Dr. William Reeves on studies of chronic fatigue syndrome and with Dr. Elizabeth Unger on studies of human papillomavirus and cervical cancer.

DCEG welcomed back four division alumni for a Careers in Epidemiology Seminar held April 15. Drs. Emily Harris, Elizabeth Harvey, Daniel Hoffman, and Sandra Melnick spoke of the application of epidemiology in their positions in managed health care, the pharmaceutical industry, academia, and the Federal government. Shelia Zahm, Sc.D., Deputy Director of DCEG and organizer of the seminar, stressed the importance of helping direct DCEG fellows to numerous opportunities in the epidemiology field because more than 75 percent of Division fellows will leave NCI to pursue their careers.

Dr. Harris, a DCEG staff fellow from 1984 to 1986, is an assistant program director at the Kaiser Permanente Center for Health Research in Portland, OR. “My experience at NCI introduced me not only to epidemiology but specifically to cancer epidemiology and genetics,” noted Dr. Harris, whose research focuses on the role of genetics in a variety of diseases. She works on projects with diverse approaches, including clinical trials, effectiveness trials, observational epidemiology studies, health services delivery, and health economics.

Dr. Harvey spent 1980 to 1986 at DCEG as a predoctoral and postdoctoral fellow before moving to a career in the pharmaceutical industry. She is Director of the Oncology Business Unit at Sanofi-Synthelabo, Inc. In that position, she helped launch two new oncology drugs and played key roles in all stages of the drug development, clinical testing, and marketing process. Dr. Harvey reflected that she was led into an industry career by the silver-bullet concept of antibody drug development nearly 20 years ago. “The industry world is fast-paced and exciting but often [has] unforgiving deadlines,” noted Dr. Harvey. She encouraged fellows to explore the many career opportunities in medical industry for epidemiologists.

Dr. Daniel Hoffman, Associate Dean of the George Washington University (GWU) School of Public Health and Health Policy and Professor of Epidemiology and Biostatistics, spoke about his experiences in academia. After spending six years conducting radiation epidemiology studies at DCEG, Dr. Hoffman joined the Centers for Disease Control and Prevention in 1986, and moved to GWU in 1994. As the M.P.H. Program Director, he has played a lead role in developing the new school of public health. He stressed the importance of teaching in academia and strongly encouraged fellows to gain teaching and mentoring experience and welcomed audience members to give guest lectures at GWU. Dr. Hoffman still collaborates with DCEG on the study of Russian workers in a nuclear facility.

Dr. Sandra Melnick spent several years in academia before coming to NIH in 1992, first as an epidemiologist with the National Institute of Allergy and Infectious Diseases and then in NCI’s extramural research program in epidemiology and genetics, which was part of DCEG before its reorganization into the Division of Cancer Control and Population Sciences. In her position as Chief of the Analytic Epidemiology Research Branch, she oversees a branch portfolio with a budget of more than $180 million annually and more than 450 funded projects. Dr.Melnick said that she enjoys her job of being “a guide through the NIH black box for principal investigators.” Rather than doing research, she takes great satisfaction in helping build the science careers of others and set future directions for the field.