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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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:
- 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?
- 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.
- 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
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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.
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BREAST CANCER
Role of Insulin Factors in Breast Pathology (full
text)
Serum concentrations of insulin-like growth factor-I (IGF-I), its major binding protein (IGFBP-3), c-peptide (a marker
of insulin secretion), and the ratio c-peptide:fructosamine (a marker of insulin resistance) were evaluated in relation
to the risk of epithelial hyperplasia (186 subjects), localized breast cancer (185 subjects), and nonepithelial breast
changes (159 subjects) among postmenopausal women. Serum concentrations of IGF-I, IGFBP-3, and the ratio IGF-I:IGFBP-3
were not related to risk of either hyperplasia or cancer. For women in the highest quartile of c-peptide or
c-peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (CI =
1.4–6.5) and 3.3 (CI = 1.5–7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast
cancer were 1.5 and 1.6, respectively. Insulin and insulin resistance may play a role in breast pathology in
postmenopausal women. (Schairer C, Hill D, Sturgeon SR, Fears T, Pollak M, Mies C, Ziegler RG, Hoover RN, Sherman ME.
Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal
women. Int J Cancer 2004;108:773-9)
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
Cervical Cancer Trends by Histologic Subtype
(full text)
Using data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program, incidence rates of squamous cell
carcinoma (SCC) and adenocarcinoma (AC) of the cervix from 1976 to 2000 were assessed by race and disease stage to
evaluate temporal changes in histologic subtypes. Among black and white women, overall incidence of invasive SCC
declined over time, while the incidence of in situ SCC increased sharply in the 1990’s. Incidence rates for AC in situ
(AIS) also increased, especially among young women. This increase in AIS incidence in white women, however, has not yet
translated into a decrease in invasive AC incidence. Among black women, invasive AC incidence rose linearly with age.
Etiologic factors may explain the rising cervical AIS incidence in young white women; rising cervical AC incidence with
age in black women may reflect either lack of effective screening or a differential disease etiology. Changes in
screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ
cervical SCC incidence in white and black women. (Wang SS, Sherman ME, Hildesheim A, Lacey JV Jr, Devesa S. Cervical
adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for
1976-2000. Cancer 2004;100:1035-44)
COLORECTAL CANCER
Vitamin D and Risk of Colorectal Adenoma (full
text)
The association of circulating vitamin D metabolites and vitamin D receptor (VDR) gene polymorphisms with advanced
colorectal adenoma were studied among participants in the Prostate, Lung, Colorectal and Ovarian Cancer trial. Among
cases with advanced adenoma of the distal large bowel (n = 763) and controls (n = 774), no association was seen with VDR
TaqI polymorphism. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were
measured in a subset of 394 cases and 397 controls. Serum levels of 25(OH)D were inversely associated with advanced
adenoma risk in women but not in men; the risk for advanced adenoma decreased by 70 percent in women (highest quintile
OR = 0.3; CI = 0.1–0.7) and did not decrease in men (OR = 1.1; CI = 0.6–2.0). Among women, 25(OH)D levels were
significantly higher in current users of hormone replacement therapy than in former or never users. Serum 1,25(OH)(2)D
was not associated with advanced adenoma risk. (Peters U, Hayes RB, Chatterjee N, Shao W, Schoen RE, Pinsky P, Hollis
BW, McGlynn KA; Prostate, Lung, Colorectal and Ovarian Cancer Screening Project Team. Circulating vitamin D metabolites,
polymorphism in vitamin D receptor, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 2004;13:546-52)
ENDOMETRIAL CANCER
Insulin-like Growth Factors and Risk of Endometrial
Cancer (full text)
Data from 174 women with endometrial cancer and 136 controls were analyzed to evaluate whether IGF-1, IGF-2, IGFBP-1, or
IGFBP-3 were associated with endometrial cancer among postmenopausal women. Higher IGF-1 levels were not associated with
endometrial cancer (OR for the highest versus the lowest tertile = 0.6; CI = 0.3–1.3). Endometrial cancer was inversely
associated with IGF-2 (OR for the highest tertile = 0.4; CI = 0.2–0.7) and IGFBP-3 (OR for the highest tertile = 0.40;
CI = 0.2–0.8). No association was seen for IGFBP-1. The potential role of the IGF system in endometrial proliferation
and carcinogenesis warrants further research. (Lacey JV Jr, Potischman N, Madigan MP, Berman ML, Mortel R, Twiggs LB,
Barrett RJ, Wilbanks GD, Lurain JR, Fillmore CM, Sherman ME, Brinton LA. Insulin-like growth factors, insulin-like growth
factor-binding proteins, and endometrial cancer in postmenopausal women: results from a U.S. case-control study. Cancer
Epidemiol Biomarkers Prev 2004;13:607-12)
ESOPHAGEAL CANCER
CDKN2A Mutations in Esophageal Cancer (full
text)
In esophageal squamous cell carcinoma (ESCC), loss of heterozygosity (LOH) is common on chromosome 9p; genetic alterations
in CDKN2A and CDKN2B on 9p are also common. To determine if these two genetic alterations are related, 56 cases of ESCC from
a highrisk Chinese population were analyzed. LOH at one or more loci on chromosome bands 9p21-p22 was found in 73 percent
of patients and occurred more frequently in patients with a family history of upper gastrointestinal cancer than in those
without. CDKN2A mutations were observed in 25 percent of cases, and the LOH pattern was significantly different for
individuals with and without a CDKN2A mutation. Three new single nucleotide polymorphisms (SNPs) and two previously
reported SNPs were identified in this group of patients. Intragenic allelic loss at polymorphic sites in CDKN2A was
detected in 32 percent of cases; 13 percent of the cases exhibited what is considered classic (n = 4) or potential
(n = 3) evidence of biallelic inactivation. Only one alteration was observed in CDKN2B. Both mutation and intragenic
allelic loss in CDKN2A appear to play a role in the development of ESCC. (Hu N,Wang C, Su H, Li WJ, Emmert-Buck MR, Li
G, Roth MJ, Tang ZZ, Lu N, Giffen C, Albert PS, Taylor PR, Goldstein AM. High frequency of CDKN2A alterations in
esophageal squamous cell carcinoma from a high-risk Chinese population. Genes Chromosomes Cancer 2004;39:205-16)
GENETICS
The SNP500Cancer Database (full
text)
The SNP500Cancer Database provides sequence and genotype assay information for candidate single nucleotide polymorphisms
(SNPs) useful in mapping complex diseases. The database is an integral component of NCI’s Cancer Genome Anatomy Project
and provides bidirectional sequencing information on a set of control DNA samples derived from 102 subjects from the
Coriell Institute for Medical Research database, which represent four self-described ethnic groups—African/African
American, Caucasian, Hispanic, and Pacific Rim. All SNPs are chosen from public databases and reports, and the choice of
genes includes a bias toward nonsynonymous and promoter SNPs in genes that have been implicated in one or more cancers.
As of July 2003, the database contains more than 3,400 SNPs, 2,490 of which have been sequenced. SNP500Cancer is an
invaluable resource for investigators to select SNPs for analysis, design genotyping assays using validated sequence
data, choose selected assays already validated on one or more genotyping platforms, and select reference standards for
genotyping assays. The SNP500Cancer Database is freely accessible at http://snp500cancer.nci.nih.gov/.
(Packer BR, Yeager M, Staats B,Welch R, Crenshaw A, Kiley M, Eckert A, Beerman M, Miller E, Bergen A, Rothman N,
Strausberg R, Chanock SJ. SNP500Cancer: A public resource for sequence validation and assay development for genetic
variation in candidate genes. Nucleic Acids Res 2004;32 Database issue:D528-32)
(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
Residential Radon Exposure and Lung Cancer Risk
(full text)
Studies of radon-exposed underground miners predict that residential radon is the second leading cause of lung cancer
mortality; however, case-control studies have not provided clear evidence of an association. Data were pooled from two
large case-control studies of residential radon conducted in China. Among 1,050 lung cancer cases and 1,996 controls, the
odds ratio (OR) increased significantly with greater radon concentration. The OR at 100 Becquerel/cubic meter (Bq/m3)
was 1.3 (CI = 1.0–1.4). For subjects who resided in the current home for 30 years or more, the OR at 100 Bq/m3 was also
1.3 (CI = 1.1–1.9). Long-term radon exposure at concentrations found in many homes appears to increase lung cancer risk.
(Lubin JH,Wang ZY, Boice JD Jr, Xu ZY, Blot WJ, De Wang L, Kleinerman RA. Risk of lung cancer and residential radon in
China: Pooled results of two studies. Int J Cancer 2004;109:132-7)
LYMPHOHEMATOPOIETIC CANCER
Alachlor Exposure May Increase Risk of Lymphohematopoietic
Cancers (full text)
Cancer incidence during 1993 to 2000 was evaluated among pesticide applicators exposed to alachlor in the Agricultural
Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 49,980
pesticide applicators were included in this analysis, including 26,510 applicators (53 percent) who reported alachlor
use. Among alachlorexposed applicators, a significant increasing trend for incidence of all lymphohematopoietic cancers
was associated with lifetime exposure-days (p for trend = 0.02) and intensityweighted exposure-days (p for trend = 0.03)
to alachlor. The risks of leukemia (rate ratio [RR] = 2.8, CI = 0.7–10.9) and multiple myeloma (RR = 5.7; CI = 0.7–45.7)
were increased among applicators in the highest alachlor-exposure category. (Lee WJ, Hoppin JA, Blair A, Lubin JH,
Dosemeci M, Sandler DP, Alavanja MC. Cancer incidence among pesticide applicators exposed to alachlor in the Agricultural
Health Study. Am J Epidemiol 2004;159:373-80)
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
Assessing the Probability that a Positive Report
Is False (full text)
Too many reports of associations between genetic variants and complex diseases such as cancer are false positives, often
because statistical significance is based on a p value alone, particularly any value below 0.05. The false positive report
probability (FPRP)—the probability of no true association between a genetic variant and disease given a statistically
significant finding—depends not only on the observed p value but also on both the prior probability that the association
between the genetic variant and the disease is real and the statistical power of the test (Figure 1). FPRP can be used to
decide whether a finding is not noteworthy and deserving of attention. It is shown that this approach can lead to
improvements in the design, analysis, and interpretation of molecular epidemiology studies. An FPRP-based criterion can
help investigators, editors, and readers of research articles protect themselves from overinterpreting statistically
significant findings that are not likely to signify a true association. (Wacholder S, Chanock S, Garcia-Closas M, El
Ghormli L, Rothman N. Assessing the probability that a positive report is false: An approach for molecular epidemiology
studies. J Natl Cancer Inst 2004;96:434-42)
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
Obesity Appears to Increase Cancer Risk Among Black
and White Men (full text)
Obesity has been linked to excess risk for many cancers, but the evidence remains tenuous for some types and few studies
have included nonwhite subjects. The risk for all major cancer sites and subsites was examined among a cohort of male
U.S. veterans (3,668,486 whites; 832,214 blacks) hospitalized with a diagnosis of obesity. Among white veterans, risk was
significantly elevated for several cancers, including cancers of the lower esophagus, gastric cardia, small intestine,
colon, rectum, gallbladder and ampulla of vater, male breast, prostate, bladder, thyroid, and connective tissue, and for
malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess risks
initially observed for cancers of the liver and pancreas persisted among men without a history of diabetes or alcoholism.
Among black veterans, risks were significantly elevated for cancers of the colon, extrahepatic bile ducts, prostate, and
thyroid, and for malignant melanoma, multiple myeloma, CLL, and AML. (Samanic C, Gridley G, Chow WH, Lubin J, Hoover
RN, Fraumeni JF Jr. Obesity and cancer risk among white and black United States veterans. Cancer Causes Control
2004;15:35-43)
OVARIAN CANCER
Survival Among Women with Borderline Ovarian Tumors
(full text)
Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that
portend excellent survival when confined to the ovary. Survival rates for women with borderline ovarian tumors and with
ovarian cancer were compared. Relative survival rates at 10 years were 97 percent for LMP-S tumors, 30 percent for serous
carcinoma (CA-S), 94 percent for LMP-M tumors, and 65 percent for mucinous carcinoma (CAM). The survival rate at 10 years
for women with distant-stage LMP-S tumors was 90 percent compared with 96 percent for women with welldifferentiated,
localized CA-S. The survival rate for women with distantstage LMP-M tumors at five years was 86 percent compared with 96
percent for women with well-differentiated, localized CA-M (Figure 2).Mucinous ovarian neoplasms were associated with an
excess of second malignancies of the digestive tract, including esophagus, stomach, small and large intestine, rectum,
pancreas, and biliary tract. Relative survival among women with distant-stage LMP tumors resembled the survival of women
who had carcinoma exhibiting favorable prognostic features (localized stage). (Sherman ME, Mink PJ, Curtis R, Cote TR,
Brooks S, Hartge P, Devesa S. Survival among women with borderline ovarian tumors and ovarian carcinoma: A populationbased
analysis. Cancer 2004;100:1045-52)
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
Cigars and Smokeless Tobacco and Risk of Pancreatic
Cancer (full text)
A population-based case-control study was conducted among 154 subjects with newly diagnosed carcinoma of the exocrine
pancreas and 844 population controls. Increased risks for pancreatic cancer were observed among those who smoked at least
one cigar/week for 6 months or more (OR = 1.7; CI = 0.9–3.3), among those who smoked more than one cigar/day (OR = 1.8; CI =
0.8–4.2), and among those who smoked cigars for more than 20 years (OR = 1.9; CI = 0.9–3.9). In addition, subjects who
regularly used smokeless tobacco had a 40 percent increased risk of pancreatic cancer (CI = 0.5–3.6) compared with
nonusers of tobacco. Risk was increased among subjects who used more than 2.5 oz of smokeless tobacco/week (OR = 3.5; CI
= 1.1–11), and long-term use of smokeless tobacco (i.e., > 20 years) was associated with a nonsignificant increased risk
(OR = 1.5; CI = 0.6–4.0). In contrast, pipe smokers experienced no excess risk. These results suggest that heavy use of
smokeless tobacco and, to a lesser extent, cigar smoking may increase the risk of pancreatic cancer among nonsmokers of cigarettes.
(Alguacil J, Silverman DT. Smokeless and other noncigarette tobacco use and pancreatic cancer: A case-control study
based on direct interviews. Cancer Epidemiol Biomarkers Prev 2004;13:55-8)
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
Childhood Tumor Risk after Maternal Ovulation-Stimulating
Drugs (full text)
To assess childhood cancer risk among children conceived following the use of ovulation-stimulating drugs, a study was
conducted among 30,364 Danish women evaluated for infertility beginning in the early 1960’s. A total of 51 cancers were
identified among the study children (standardized incidence ratio [SIR] = 1.14; CI = 0.8–1.5). There was no increased
risk of childhood tumor observed with the use of any fertility drug (rate ratio [RR] = 0.82; CI = 0.4–1.6) or specifically
with clomiphene citrate (RR = 0.77; CI = 0.4–1.6). Tumors occurring early in life and nonhematopoietic malignancies
(including neuroblastomas) were not associated with drug use. Nonsignificant elevations in the risk of cancers occurring
later in life, especially childhood hematopoietic malignancies (RR for use of any ovulation-stimulating drugs = 2.30, CI
= 0.8–6.6), may have been related to the underlying reasons for medication use. The findings of this study suggest no
association between maternal use of ovulation drugs and childhood cancer, but additional adequately powered studies are
needed. (Brinton LA, Kruger Kjaer S, Thomsen BL, Sharif HF, Graubard BI, Olsen JH, Bock JE. Childhood tumor risk after
treatment with ovulation-stimulating drugs. Fertil Steril 2004;81:1083-91)
RADIATION
Thyroid Cancer Among Children Exposed to I-131 after
the Chornobyl Accident (full
text)
In children, the thyroid gland is one of the organs most sensitive to external exposure to x- and gamma rays. Data on the
risk of thyroid cancer in children after exposure to radioactive iodines are sparse, however. The Chornobyl accident in
Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly I-131. A trinational collaborative
cohort study being conducted in Belarus and Ukraine includes 25,161 subjects younger than age 18 in 1986. Study subjects
are screened for thyroid diseases every two years and individual thyroid doses are estimated based on 1986 measurements
of thyroid gland radioactivity, along with a radioecological model and interview data. Approximately 100 histologically
confirmed thyroid cancers were detected in the first round of screening. These data will enable fitting appropriate dose-response
models, which are important in radiation epidemiology and public health for predicting risks from exposure to radioactive
iodines from medical sources and possible future nuclear accidents. The cohort will be followed for at least three
screening cycles, which will lead to more precise risk estimates. (Chornobyl Thyroid Diseases Study Groups of Belarus,
Ukraine, and the United States. A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident:
Objectives, design and methods. Radiat Res 2004;161:481-92)
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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.
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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.
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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.
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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. |