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This subset of 300 men and 300 women is part of a molecular and metabolic study in which participants blood will be tested for many biomarkers to examine how they relate to differing levels of physical activity. Key emerging pathways to be studied include insulin resistance, growth factors, and chronic inflammation. Dr. Schatzkin points out that similar studies are now also being conducted in the AARP cohort. For example, some participants donate cheek cells from which DNA can be extracted. This molecular genetic information, Dr. Schatzkin notes, will help us establish with even greater certainty a causal connection between energy balance and cancer and will also help us understand the biological processes underlying this connection. The field of energy balance is vast, and NEB researchers are vigorously investigating many aspects and hypotheses. We dont yet know, for example, how higher levels of physical activity reduce cancer risk, and whether the mechanisms are different for breast cancer and colon cancer, suggests Dr. Albanes. DCEG researchers continue to probe such questions by taking advantage of the longitudinal cohorts and other studies that have collected dietary, activity, and anthropometric data. They are improving upon these studies while incorporating novel methods to examine molecular pathways. Also, NEB investigators are involved in NCI and NIH working groups on energy balance to ensure coordination of the DCEG efforts with others across NIH. Today, approximately one-third of the adult U.S. population is considered obese, as shown in Figure 2; almost two-thirds are considered overweight or obese. With these numbers growing, this area of research is ever more timely. Cari Kornblit |
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On November 8 and 9, 2004, the NCI Division of Cancer Epidemiology and Genetics (DCEG) convened a workshop entitled Cancer survivorship: Genetic susceptibility and second primary cancers. The goals of the workshop, sponsored by the NIH Office of Rare Diseases, were to identify research issues, priorities, and resources needed to advance the study of genetic susceptibility and second primary cancers; to identify unusual research opportunities that NCI can address in future collaborative endeavors; and to make specific recommendations for implementation by intramural and extramural divisions of NCI. Lois B. Travis, M.D., Sc.D., Radiation Epidemiology Branch (REB), was chair of the Scientific Program Committee, and Linda Morris Brown, Dr.P.H., Biostatistics Branch (BB), served as assistant chair. Other NCI investigators on the committee included Blanche Alter, M.D., M.P.H., Clinical Genetics Branch (CGB), Neil Caporaso, M.D., Genetic Epidemiology Branch (GEB), Stephen Chanock, M.D., NCI Core Genotyping Facility (CGF), Dr. Graca Dores (NCI Division of Cancer Prevention), Mark H. Greene, M.D. (CGB), Michie Hisada, M.D., M.P.H., Sc.D., Viral Epidemiology Branch (VEB), Peter Inskip, Sc.D. (REB), Charles Rabkin, M.D. (VEB), and Margaret Tucker, M.D. (GEB). Dr. Mary Gospodarowicz (Princess Margaret Hospital, Toronto), Dr. Alfred Knudson (Fox Chase Cancer Center), and Dr. Peter Shields (Georgetown University Medical Center) served as extramural advisors. Representatives from the NCI Office of Cancer Survivorship (Dr. Julia Rowland, director, and Dr. Noreen Aziz, senior program director, Division of Cancer Control and Population Sciences) participated in the meeting with researchers from the NCI Center for Cancer Research (Dr. William D. Figg) and the NCI Division of Cancer Treatment and Diagnosis (Dr. Barry Anderson). Dr. Michael Thun (American Cancer Society) and Susan Leigh (National Coalition for Cancer Survivorship), who are members of the NCI Board of Scientific Counselors, also participated. Ursula Leitzmann, M.A. (REB) served as Administrative Coordinator, and Jose Reyes (BB) assisted with travel arrangements and document preparation. Workshop participants were experts from various specialties, including molecular carcinogenesis, epidemiology, pharmacogenomics, statistics, clinical oncology, and radiation oncology. The advocacy community was also well-represented. There were four sessions that summarized state-of-the-art knowledge. Session 1, Populations of Cancer Survivors: Description and Overview of Current Work in Primary Cancers and Other Late Effects, was moderated by Dr. Christine Ambrosone (Roswell Park Cancer Institute) and Dr. Rabkin. The speakers were: Dr. Gospodarowicz, Dr. Robert Wittes (Memorial Sloan-Kettering Cancer Center), Dr. Andrea Ng (Brigham and Womens Hospital), Dr. Louise Strong (University of Texas M.D. Anderson Cancer Center), and Dr. Leslie Robison (University of Minnesota). They described multidisciplinary programs at their institutions that have integrated clinical care and research and provided innovative web-based education for patients, including scientific information on late sequelae of treatment. The development of web-based informatics resources to collect long-term follow-up data on large cohorts of patients was emphasized. |
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Session 2, Inherent Genetic Susceptibility to Second Primary Cancers, was moderated by Drs. Shields and Tucker and featured the following: Dr. David Malkin (Hospital for Sick Children, Toronto), Dr. Ken Offit (Memorial Sloan-Kettering Cancer Center), Ruth Kleinerman, M.P.H. (REB), and Dr. Toshi Taniguchi (Fred Hutchinson Cancer Research Center). Participants discussed a number of familial cancer syndromes that have helped elucidate basic carcinogenic mechanisms, such as Li-Fraumeni syndrome and hereditary breast and ovarian cancers. Another central topic was hereditary retinoblastoma, the most prominent example of an inherited mutation that predisposes to radiotherapy-related cancers. Session 3, Radiation, Chemotherapy, Genetic Susceptibility and Second Primary Cancers, was moderated by Dr. John Little (Harvard School of Public Health) and Dr. Caporaso, and featured Dr. Eric Hall (Columbia University), Dr. James Allan (University of York, United Kingdom), Dr. Figg, Dr. Ching-Hon Pui (St. Jude Childrens Research Hospital), and Nathaniel Rothman, M.D. (Occupational and Environmental Epidemiology Branch). Speakers described how the carcinogenic effects of chemotherapy and radiotherapy might be influenced by the level of carcinogen exposure as well as by polymorphisms in genes involved in carcinogen metabolism and DNA repair, and the patients nutritional status. The discussion also addressed interactions between cytotoxic drugs and radiation. Drs. Gospodarowicz and Greene moderated a Special Topics session, At the Intersection of Cancer Survivorship Research, which included Dr. Chanock, Dr. Colin Begg (Memorial Sloan-Kettering Cancer Center), Dr. Angela DeMichele (University of Pennsylvania), and Dr. Carol Kasten-Sportes (NCI Division of Cancer Control and Population Sciences). Speakers discussed current and future tools available for genetic analysis, study-design issues for etiologic investigations of second primary cancers, practical issues regarding multidisciplinary clinical and research programs in cancer survivorship, and research funding opportunities provided by the NCI. Following the presentations, attendees broke into three workgroups to address the workshop goals and make specific recommendations about the study of second cancers. A full meeting report is being prepared for publication. |
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AARON BLAIR LEAVES OEEB LEADERSHIP AFTER 26 YEARSAaron Blair, Ph.D., has stepped down as Chief of the Occupational and Environmental Epidemiology Branch (OEEB), as of October 2004, to refocus on his research interests as a Principal Investigator. Dr. Blair has developed and led NCIs occupational epidemiology program for 26 years, first as Head of the Occupational Studies Section and later as Branch Chief when the Section was upgraded (originally the Occupational Epidemiology Branch, now the OEEB). Over this period, the staff has grown from 4 professionals to more than 30. The OEEB has led the way in the incorporation of state-of-the-art industrial hygiene into robust epidemiologic research designs, in the development of biochemical and molecular epidemiology, in the assessment of risks associated with important and widespread industrial exposures, and in pioneering advances in evaluating the risks associated with agricultural exposures. More recently, the Branch has been a leader in demonstrating how these same methods can be developed and used for the difficult but important tasks of studying carcinogenic risks in the general environment. Much of this was accomplished because of Dr. Blairs personal leadership and his development of a supportive and creative environment for the outstanding investigators he has recruited to the program. This same atmosphere has also made the OEEB a highly sought-after opportunity for training a new generation of occupational and environmental epidemiologists. Under Dr. Blair, OEEB has fostered collaborations with some of the most experienced epidemiologists in the world. Dr. Blairs accomplishments at OEEB have come about through his unique combination of scientific judgment and insight, outstanding administrative and management skills, honesty, integrity, humility, good humor, sincere caring for people, and dedication to the team effort. He will be greatly missed as Branch Chief and, indeed, a hard act to follow. We are very fortunate, however, that he is remaining as a senior investigator and will continue to contribute his talents to the Branch, Division, Institute, and NIH. |
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DCEG researchers have been studying inherited ovarian and breast cancer for decades, but with the creation of the Clinical Genetics Branch (CGB) five years ago, they are now able not only to study the disease in families, but also to look toward preventing the disease by applying molecular biology advances. A large prospective study led by Mark H. Greene, M.D., in collaboration with the Gynecologic Oncology Group (GOG) and the Cancer Genetics Network (CGN), aims to do just that. As soon as clinical tests to identify BRCA mutation carriers became commercially available, concerns arose as to how to manage the care of patients who are at greater genetic risk of breast and ovarian cancers. Retrospective studies from high-risk clinics in tertiary care facilities offered some useful preliminary information, but it was clear that a large prospective study was needed to provide answers that were unbiased, statistically sound, and representative of the diverse population of women at risk. Dr. Greene and his colleagues set out to design a protocol that would not only answer lingering questions, but would also develop data on important issues not yet addressed by prior studies, such as non-cancer morbidity (e.g., heart attack and osteoporosis) and the quality of life experienced by women who undergo premature menopause as a consequence of opting for risk-reducing removal of the ovaries. Dr. Greene has had a career-long interest in ovarian cancer, having worked as a clinician and researcher in NCIs program of studies in familial cancer. He explains that patients with ovarian cancer are exceptionally motivated and determined to get well. It has been inspirational to be part of the care of these patients. The study, dubbed GOG 0199, incorporates two arms and is a collaboration between several divisions within NCI, extramural researchers, and more than 100 GOG centers around the world. The first arm of the study offers women at high risk of ovarian cancer the option to undergo an oophorectomy, the surgical removal of the ovaries and fallopian tubes. These women are then monitored every six months for five years. Recruitment and treatment are being carried out at 110 institutions around the United States and, as of the beginning of 2005, at 5 centers in Australia. The Clinical Center on NIHs main campus is also a study site, so that family members who are participating in DCEGs hereditary breast/ovarian cancer family studies program can enroll and benefit from this project. The second arm of GOG 0199 involves a screening protocol originally devised by the Cancer Genetics Network, an NCI-funded consortium of eight institutions. It offers women the option of regular blood screening for ovarian cancer through an improved version of the CA-125 screening tool that uses a mathematical model, ROCA (Risk of Ovarian Cancer Algorithm), to measure changes in blood levels over time instead of a single measurement. Since July 2003, when enrollment began, more than 700 subjects have joined both arms of the study. Eventually, study researchers would like to enroll a total of 1,800 women. Because this number is larger than any one center can handle, coordination between all of the clinical sites is necessary if the study is to meet its accrual goals and achieve statistical significance. On getting such an expansive study rolling, Dr. Greene is happy to report: Well, it is clear that we can do the study. Some people thought wed never get this off the ground, since it is so complicated. |
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In addition to extramural collaborations, Dr. Greene works with Dr. Jeffery Struewings laboratory in the Center for Cancer Research to obtain BRCA mutation data on all study participants, with Dr. Ted Trimble and others in the Division of Cancer Treatment and Diagnosis to facilitate the relationship with the GOG centers, and with the Division of Cancer Prevention, which is providing major funding support through its Community Clinical Oncology Program. He explains that patients with ovarian cancer are exceptionally motivated and determined to get well. It has been inspirational to be part of the care of these patients. Both arms of the study are collecting clinical information on all enrolled patients, along with biological samples such as blood and ovarian tissue, which are taken at the time of surgery. Dr. Greene is confident that this study will yield a treasure trove of data. Overall, the GOG 0199 trial serves as a model for future intervention studies of genetically at-risk populations because it has managed to successfully incorporate so many centers and such multidisciplinary expertise. Although at times the collaboration has been difficult, Dr. Greene says matter-of-factly, To bring diverse groups togetherinstead of being competitorsthat is what it will take to move the field forward. And in the process, many women and their families will benefit from these efforts. |
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DCEG DOUBLES NUMBER OF FARE WINNERSEight DCEG fellows were recipients of the 2005 NIH Fellows Award for Research Excellence (better known as FARE), double the number who won the award last year. The FARE program recognizes outstanding scientific research by fellows in the NIH intramural research program. To enter the competition, fellows submit abstracts of their research, which are reviewed by a panel of NIH postdoctoral fellows and tenured/tenure-track investigators. Winners receive a travel stipend to attend a scientific meeting, where they present their research papers. More information about the FARE competition is available at http://felcom.nih.gov/FARE. DCEG FARE Winners and Abstract Titles Biostatistics Branch
Genetic Epidemiology Branch
Hormonal and Reproductive Epidemiology Branch
Nutritional Epidemiology Branch
Occupational and Environmental Epidemiology Branch
Radiation Epidemiology Branch
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Although he was originally trained in theoretical statistics, Nilanjan Chatterjee, Ph.D., now works on solving difficult and interesting statistical problems in cancer epidemiology. I try to select problems in which my knowledge of theoretical statistics is strong, but which also have wide application, he says. “Not everyone who smokes gets lung cancer; the ones who do [get cancer] not only have the environmental exposure (smoking), but also must have some susceptibility genes. Studying any gene-environment interaction is difficult because it requires so much data. I am coming up with more efficient ways to do these studies..” Dr. Chatterjee, a senior investigator in the Biostatistics Branch, has been with NCI since 1999 and received tenure on November 1, 2004. His first area of research, which he started as a graduate student at the University of Washington, Seattle, involved developing methods to analyze two-phase data, which are often collected in epidemiologic studies. Two-phase design reduces expense. We can collect inexpensive data on a large number of people, and then more expensive data on a subsample. There is a complex statistical problem in how to analyze those data. Some of the previous methods proposed in this area utilize only data from phase two subjects who have complete covariate information, thus losing valuable information from phase one subjects who were not selected for phase two, Dr. Chatterjee explains. He developed an analytic method that treats a two-phase study as a missing data problem, in which subjects not selected for phase two have only partial covariate information. This method combines the phase one and phase two sources of data, he says. A second area of interest that caught Dr. Chatterjees attention soon after coming to NCI is the kin-cohort approach in studies of familial cancer risk. He developed methods for estimating disease risks associated with genetic and environmental factors, as well as ways to quantify familial aggregation of disease due to unmeasured risk factors. The methods account for the age at onset of disease as well. Dr. Chatterjee has also worked on streamlining the analysis of gene-environment interactions. For example, we did a study looking at BRCA1 status and oral contraceptive use, he says. We can assume these two factors are independent, because the women didnt know their BRCA1 status. Our study showed that if we assume the two factors are independent, we can more precisely measure odds ratios and risk, compared with a standard logistic regression analysis. Dr. Chatterjee and others also showed that the same independent assumption may be made in a matched case-control study. Those studies led Dr. Chatterjee into the general field of genetic and molecular epidemiology. Molecular data linked to exposure data is a new thing, and its generating a lot of new statistical problems, he says. Not everyone who smokes gets lung cancer; the ones who do not only have the environmental exposure (smoking), but also must have some susceptibility genes. Studying any gene-environment interaction is difficult because it requires so much data. I am coming up with more efficient ways to do these studies. |
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The advent of microarrays and other biotechnologies that allow for the collection of huge amounts of data has kept Dr. Chatterjee busy as well. Today, there are lots of ways to classify cancer. It is feasible, for example, to use gene expression patterns to diagnose cancer and to tailor treatment. However, its been less clear how to use this information as a component of epidemiologic studies. Dr. Chatterjee has developed methods for studying whether the environmental exposures are different for different subtypes of cancer. For example, smoking may increase the risk of only certain types of lung cancer, and we can figure out which types by studying both molecular and exposure data, he suggests. The method I have developed allows one to simultaneously study multiple disease characteristics that might be related, such as estrogen-receptor (ER) and progesterone-receptor (PR) status in breast cancer, he says. Previously used methods are suitable mainly for analyzing subtypes defined by only single disease characteristics. Using my method, one can study whether there is independent variation in the effect of an exposure by ER and by PR status, after adjusting for one another, he says. Similarly, using my method, one can study whether the variation in the effect of an exposure between ER categories is modified by PR status and vice versa. Was it challenging for a theoretical statistician to learn genetics? It really was not a difficult transition, he answers. Once I started learning about kin-cohort studies, which were originally developed by colleagues in DCEG, that gave me an introduction, and Ive gone on from there. In the future, Dr. Chatterjee has more ideas to investigate. One topic I think is important is how to analyze genetic data when we are choosing multiple genes in a causal pathway, such that the genes are not independent of one another, he says. Im interested in how to analyze those types of data, and also in data mining tools to look at complex interactions. Nancy Volkers |
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TEAM CONDUCTS PROSTATE CANCER STUDY IN GHANAAnn Hsing, Ph.D., Hormonal and Reproductive Epidemiology Branch, is leading a DCEG team that is screening for prostate cancer in Africa in the Ghana Study. The DCEG team is collaborating with scientists at the University of Ghana Medical School (UGMS) and its teaching hospital, Korle-Bu Hospital, led by Professor Edward Yeboah, a leading Ghanaian urologist. Recruiting of subjects is underway for 1,000 healthy men between 50 and 74 years old, randomly selected from the population in Accra, Ghana. NCI researchers spent more than two years planning the study and working with UGMS collaborators to prepare for the data collection effort. Field work should be completed by December 2005. |
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As a graduate student in Portugal in 1993, Ligia Pinto, Ph.D., was awarded a fellowship that allowed her to complete her dissertation work in any laboratory in the world. She chose Dr. Gene Shearers lab in NCIs Experimental Immunology Branch, and she hasnt left NCI since. Her early work involved HIV infection and AIDS, but today Dr. Pinto is head of DCEGs Human Papillomavirus (HPV) Immunology Laboratory in the Hormonal and Reproductive Epidemiology Branch (HREB), where she works on immunologic responses to vaccines that could one day help treat and prevent cervical cancer. Im very much interested in infectious diseases, and HPV is an important public health concern, says Dr. Pinto. With HIV, most infections progress to AIDS. With HPV, only a small proportion of infected individuals progress to cancer; most people clear the infection. Its been interesting to try to understand why that happens. There are more than 100 strains of HPV; at least 12 have been associated with cervical cancer, with HPV-16 showing the strongest link. Each year, cervical cancer is diagnosed in almost a half million women worldwide. Approximately 250,000 women die of the disease each year, with higher mortality rates in non-industrialized countries. One promising HPV vaccine developed at NCI is now being tested in a phase III trial in Costa Rica. This vaccine has been found to induce robust antibody responses and was efficacious in reducing incidence of infection. Although protection is likely conferred through neutralizing antibodies, cell-mediated immune responses may play an important role as regulators of strong and sustained humoral responses. The HPV laboratory has played an important role in monitoring immunogenicity of the vaccine in the NCI-Johns Hopkins University phase II trial. In these studies, the laboratory showed that vaccination induced HPV-specific T-cell responses detectable by proliferation of both CD4+ and CD8+ T cells and in vitro production of Th1, Th2, and inflammatory cytokines. To help researchers understand how immunity is induced and how it might change over time, the phase III trial will follow women for several years after vaccination. Another important function of the lab is to develop and validate immunologic methods that are applicable to field studies and serve to evaluate cellular and humoral immune responses systemically and at the genital tract. These include assays of neutralizing antibodies, whole blood assays for multiplex cytokine detection, preparation of samples in remote sites for flow cytometric analysis, and development of methods to evaluate immune responses at the cervix. The overall aim of these studies is to gain a better understanding of host immunity to HPV through identification of immune determinants of protection from infection and associated disease. Dr. Pinto works closely with other investigators in HREB, especially Allan Hildesheim, Ph.D., to understand how the HPV vaccine works. We want to know how it induces protection and the duration of the protection, Dr. Pinto says. We hope that what we learn from this trial will help us improve HPV vaccines and design better therapeutic strategies. Dr. Pinto says she has always loved science, biology in particular, and wanted to conduct laboratory research. After graduating with a degree in biology from the Faculty of Sciences and the Faculty of Medicine of Lisbon, Dr. Pinto started her graduate work with the Faculty of Medicine of Lisbon in 1988. In 1993, she was awarded the fellowship that brought her to the United States and to NCI. My goal with the fellowship was to get solid training in immunology and infectious diseases and return to Portugal. However, I ended up staying at NCI for postdoctoral work in the Experimental Immunology Branch. Now Im head of a lab working on exciting aspects of HPV research, which shows promise in reducing the burden of cervical cancer around the world. Nancy Volkers |
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Congratulations to the following DCEG staff members, who were recognized for their accomplishments over the past year at the annual NIH Awards Ceremony, held on October 28, 2004:
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The Hormonal and Reproductive Epidemiology Branch (HREB) hosted the second seminar in its distinguished lecturer series on January 6, 2005, featuring Dr. Rudolf Kaaks of the International Agency for Research on Cancer (IARC). His seminar was titled Overweight, physical inactivity, and cancer risk: Hormonal mechanisms. Dr. Kaaks first summarized data in the literature, which provide sufficient evidence that obesity is associated with cancers of the colon, endometrium, kidney, and esophagus, and with breast cancer in postmenopausal women. He then presented data from his ongoing work, particularly in the European Prospective Investigation into Cancer (EPIC) study, that suggest potential mechanisms by which obesity predisposes to cancer. His research illustrates that the link between obesity and cancer risk is mediated by sex hormone levels and other metabolic pathways, including inflammation, insulin, and insulin-like growth factors. Specifically, he concluded that (1) hyperinsulinemia and alterations in endogenous sex steroid metabolism are the likely underlying mechanisms that link obesity and various cancers; (2) elevated plasma androgens and estrogens are associated with cancers of the endometrium and breast in postmenopausal women, with elevated estrogens resulting from excess weight, though the cause of elevated androgen levels is not entirely clear; (3) among premenopausal women, endometrial cancer risk is increased in those with ovarian androgen excess; and (4) elevated circulating IGF-1 levels are associated with colon, prostate, and postmenopausal breast cancer. He also emphasized the importance of investigating energy balance, exogenous hormones, and genetic susceptibility in future studies to clarify the underlying mechanisms linking obesity to higher cancer risk. During his two-day visit, he met with numerous DCEG investigators to offer his insights on conducting hormone-related epidemiologic studies. Dr. Kaaks is especially interested in elucidating the relationships between cancer risk and diet, other lifestyle factors, obesity, physical activity, endogenous hormones and growth factors, and gene-environmental interactions. Dr. Kaaks, a leader in the field of nutritional epidemiology, was trained at Wageningen University, the Netherlands. He joined IARC in 1988 as a scientist in the Unit of Nutrition and Cancer and became head of the Hormones and Cancer research team in 2002. He directs a laboratory with expertise in measuring serum sex steroids and insulin-like growth factors. As a coinvestigator of the EPIC Study, a multi-center collaboration among 10 European nations to investigate the role of nutrition and other lifestyle risk factors for cancer and other chronic diseases, he is especially interested in elucidating the relationships between cancer risk and diet, other lifestyle factors, obesity, physical activity, endogenous hormones and growth factors, and gene-environment interactions. He serves on a number of important committees, including the Specimen Advisory Board of the American Cancer Society. Jennifer Connor and Lori Sakoda, M.P.H. |
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FRED KADLUBAR DELIVERS OEEB DISTINGUISHED LECTUREDr. Fred F. Kadlubar, Director, Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, Arkansas, was honored as the DCEG Distinguished Lecturer in Occupational and Environmental Cancer. Dr. Kadlubar presented a seminar on October 7, 2004, entitled Breast cancer: Biomarkers of carcinogen exposure and treatment efficacy. Dr. Kadlubar received his Ph.D. from the University of Texas at Austin. His research interests include:
Dalsu Baris, M.D., Ph.D. |
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Measuring Urinary Estrogens Simultaneously ( Full Text )
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BEVERLEY CRANSTON EARNS SPECIAL APPRECIATION AWARDBeverley Cranston of the University of the West Indies, Jamaica, received a DCEG special recognition award for her 21 years of service as a project manager for the Viral Epidemiology Branch (VEB) research program on human T-cell lymphotropic virus type I (HTLV-I). Endemic in the Caribbean, southern Japan, parts of Africa, the Middle East, and South America, HTLV-I is causally associated with adult T-cell leukemia/lymphoma and a neurologic disease called HTLV-Iassociated myelopathy/tropical spastic paraparesis. On behalf of DCEG, Michie Hisada, M.D., M.P.H., Sc.D., a tenure-track investigator in VEB, presented the award to Ms. Cranston during the program site visit in October 2004. |
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Blanche Alter, M.D., M.P.H., Clinical Genetics Branch (CGB), presented invited talks on medical and genetic issues and cancer risk in inherited bone marrow failure syndromes at the Annual Education Conference, National Society of Genetic Counselors in Washington, DC, the NIDCD Clinical Seminar Series, Bethesda, Maryland, the German Fanconi Anemia Family Meeting in Kronach, Germany, the Charite Campus Virchow-Klinikum in Berlin, and the Pediatric Tumor Board Lecture, Loma Linda University Childrens Hospital in California. Aaron Blair, Ph.D., Occupational and Environmental Epidemiology Branch (OEEB), gave an invited talk on The Agricultural Health Study at the 14th Annual Meeting of the Pennsylvania Association of Sustainable Agriculture held in State College in February. Dr. Blair also attended, as a board member, a National Toxicology Science Advisory Board meeting in Research Triangle Park, North Carolina in October. Matthew Bonner, Ph.D. (OEEB), has been appointed as a DCEG representative to the NIH Fellows Committee. He joins Beth Brown, Ph.D., of the Viral Epidemiology Branch (VEB). Louise Brinton, Ph.D., Hormonal and Reproductive Epidemiology Branch (HREB), gave a talk on Infertility treatment and breast cancer risk at the 60th Annual Meeting of the American Society of Reproductive Medicine in Philadelphia in October. Beth Brown, Ph.D. (VEB), gave a presentation titled Common variations in immune-mediated genes and risk of B-cell and Hodgkin lymphomas, Epilymph-Barcelona at the Epilymph Meeting in Lyon, France in November. Dr. Brown also gave an invited presentation on Human herpesvirus-8 and classic Kaposi sarcoma: Phenotypic and genotypic markers of immunity at the Rollins School of Public Health, Emory University, Atlanta in December. Capt. Linda Morris Brown, Dr.P.H., Biostatistics Branch (BB), gave an invited talk on The role of race/ethnicity in the epidemiology of esophageal cancer at the NIH Academy, Bethesda, Maryland in December. Eric Engels, M.D., M.P.H. (VEB), gave a lecture on Leadership
and service for the publics health to the Jefferson Scholars
at the University of Virginia, Charlottesville in August. Dr. Engels later
gave an invited talk on Simian virus 40 and non-Hodgkin lymphoma:
Weighing the evidence at the Harvard School of Public Health in
October. In addition, he was invited to talk on Epidemiology of
cancer in persons with HIV/AIDS: A look to the future at the Planning
Meeting for Emerging and Re-emerging Malignancies in HIV/AIDS at NCI and
the National Institute of Allergy and Infectious Diseases in Rockville,
Maryland in October. Dr. Engels also gave a talk on Polyomaviruses
and childhood cancer: Plenty of smoke, but is there fire? at the
Pediatric Oncology Branch, Center for Cancer Research, NCI in Bethesda,
Maryland in November. SCHOLAR-IN-TRAINING AWARD FOR WRIGHT Margaret Wright, Ph.D., Nutritional Epidemiology
Branch (NEB), won an AACR-AFLAC Scholar-in-Training Award from the
American Association for Cancer Research (AACR) at the third annual
Frontiers in Cancer Prevention Research Conference in Seattle in October. Ethel Gilbert, Ph.D., Radiation Epidemiology Branch (REB), gave a talk on Contributions of new epidemiology studies to radiation risk assessment in honor of Dr. Gilbert Beebe, who was a scientist in DCEG for more than 30 years. The Third Annual Gilbert W. Beebe Symposium, held in Washington, DC in December, focused on recent developments in radiation risk assessment. Mark Greene, M.D. (CGB), recently spoke on risk-reducing strategies for hereditary ovarian cancer at: Harrington Cancer Center in Amarillo, Texas; the Ovarian Cancer National Alliance Annual Advocacy Conference in Washington, DC; Holy Cross Hospital in Silver Spring, Maryland; and the Scottsdale HealthCare Symposium on Cancer Genetics in Arizona. He also spoke on familial breast and ovarian cancer and melanoma at Yale University, the Virginia Piper Cancer Center in Scottsdale, Arizona, and North Arundel Hospital, Glen Burnie, Maryland. In addition, Dr. Greene, Joan Kramer, M.D. (CGB), and Mary Lou McMaster, M.D., Genetic Epidemiology Branch (GEB), recently gave talks to the Third Investigators Meeting of the International Testicular Cancer Linkage Consortium, held in November at the United Kingdom Institute for Cancer Research in London. They focused on the CGB-led Familial Testicular Cancer Projects. Patricia Hartge, Sc.D., Epidemiology and Biostatistics Program (EBP), gave two lectures on cancer epidemiology at George Washington Universitys School of Public Health and Health Services in Washington, DC in November and December. Michael Hauptmann, Ph.D. (BB), gave a two-day course in genetic epidemiology for the postgraduate public health training program at the University of Munich, Germany in November. Robert N. Hoover, M.D., Sc.D. (EBP), and Dr. Edward Trapido
from NCIs Division of Cancer Control and Population Sciences gave
an invited briefing on Advances in molecular science and technology
to NCIs National Cancer Advisory Board in Bethesda, Maryland in
November. Sadie Hutson, Ph.D., R.N., C.R.N.P. (CGB), received her Ph.D. in Nursing from the University of Pennsylvania in May 2004. Her DCEG thesis advisors were Blanche Alter, M.D., M.P.H., and Mark Greene, M.D. She is continuing to work as a postdoctoral fellow in the CGB. She gave a talk on the topic of her thesis, Containment and invisibility: The experiences of siblings of patients with Fanconis anemia, to the 16th Annual Fanconi Anemia Scientific Symposium in Cambridge, Maine in October. Dr. Hutson and Jennifer Loud, M.S.N., C.R.N.P., also guest edited a special issue on cancer genetics in Seminars in Oncology Nursing in August. Ruth
Kleinerman, M.P.H. (REB), gave a talk on Assessment of radiation
exposure using biological dosimetry at the 13th Annual Ionizing
Radiation Measurement and Standards Council Meeting in Gaithersburg,
Maryland in October. Ms. Kleinerman also spoke on Genetic susceptibility
to second cancers in a cohort of retinoblastoma patients at the
Cancer Survivorship Workshop in Rockville, Maryland in November. HPV DNA SCREENING STUDY IN MISSISSIPPI DELTA Philip Castle, Ph.D. (HREB), and colleagues
are developing human papillomavirus (HPV) screening strategies for
underserved women in the Mississippi Delta region in collaboration
with the NCI Center for Reducing Cancer Health Disparities (CRCHD)
and the University of Alabama. The team, in collaboration with Denise
Whitby, Ph.D., Viral Epidemiology Section (VES), and other NCI-Frederick
VES members, will develop a core HPV DNA testing facility. Dr. Castle
also recently joined the editorial advisory board of the Journal
of Infectious Diseases. Qing Lan, M.D., Ph.D. (OEEB), gave a lecture titled Hematotoxicity in workers exposed to low levels of benzene at George Washington University in Washington, DC in December. Maria Teresa Landi, M.D., Ph.D. (GEB), gave the keynote address on Genetic epidemiology of cutaneous melanoma at the XLII Italian National Congress of Dermatology in Rimini, Italy in October. Dr. Landi also gave talks on Epidemiologic studies of the genetic and environmental factors associated with malignant melanoma at the Symposium on Cancer Biology at the University of Colorado at Boulder in November and the Colorado Cancer Center Symposium Series at the University of Colorado Cancer Center in Denver in November. Michael Leitzmann, M.D., Dr.P.H. (NEB), gave a talk on Diet and prostate cancer at Boston University in December. That month, he also spoke about Energy balance and cancer at George Washington University, Washington, DC. Martha S. Linet, M.D., M.P.H. (REB), gave a Grand Rounds presentation on Cancer in children: Characteristics and causes to the American Academy of Pediatrics National Conference & Exhibition in San Francisco in October. Dr. Linet also gave a presentation on Hematologic malignancies: Patterns, risk factors, and future directions at the University of Illinois Cancer Center, Chicago in December. Mary Lou McMaster, M.D. (GEB), was recently invited to chair the Predisposition to Waldenströms macroglobulinemia session at the Third International Workshop on Waldenströms Macroglobulinemia in Paris, where she also spoke on Long-term follow-up of familial Waldenströms macroglobulinemia. Jay Nuckols, Ph.D. (OEEB), gave an invited seminar on Exposure assessment for environmental epidemiology: Integrating earth and health sciences to the University of Colorado Health Sciences Centers School of Medicine in Denver in January. Dr. Nuckols also gave an invited talk on Use of GIS in exposure assessment for environmental epidemiology at the Bay Area Automated Mapping Association meeting in San Francisco in January. June
Peters, M.S. (CGB), gave three talks at professional meetings in
October. Two were at the National Society of Genetic Counselors Annual
Education Conference in Washington, DC on Genetic counseling,
psychosocial assessment, and empathy and on Increased cancer
risk in FA, DC, and XP. The third was on Research opportunities
in hereditary cancers at the annual meeting of the International
Society of Nurses in Genetics, Toronto. Ruth
Pfeiffer, Ph.D. (BB), gave a talk titled Mixed effects models
for specially ascertained samples: Statistical issues and examples in
epidemiologic studies at the Statistics Seminar at Yale University
in September. Dr. Pfeiffer also spoke on Criteria for evaluating
models of absolute risk at a Statistical Methods in Epidemiology
Seminar at Harvard University in January. CANCER PREVENTION CONFERENCE DCEG staff members participated in the third
international Frontiers in Cancer Prevention Research conference,
held by the American Association for Cancer Research (AACR), in Seattle
in October. Some of the DCEG presenters and speakers were Kenneth
Adams, Ph.D. (NEB), Wen-Yi Huang, Ph.D. (OEEB), Marc
Gunter, Ph.D. (NEB), Daehee Kang, M.D., Ph.D. (OEEB),
Tanuja Rastogi, Sc.D. (NEB), and Margaret Wright, Ph.D.
(NEB). Tanuja Rastogi, Sc.D. (NEB), gave a talk on Asian Indians and chronic diseases: Role of lifestyle and diet to the National University of Singapore Department of Community, Occupational, and Family Medicine in September. OEEBs Nathaniel Rothman, M.D., M.P.H., M.H.S., Qing Lan, M.D., Ph.D., and Richard Hayes, D.D.S., Ph.D., were invited speakers at the meeting Recent Advances in Benzene Toxicity held in Munich, Germany in October. Dr. Hayes was a member of the organizing committee and spoke on Benzene and cancer in China; Dr. Rothman chaired a session on epidemiologic studies and spoke on Use of intermediate endpoints to study the health effects of benzene; and Dr. Lan spoke on Benzene exposure and hematotoxicity. Arthur Schatzkin, M.D., Dr.P.H. (NEB), spoke on Diet and cancer: A role for molecular epidemiology? to the United Kingdom Molecular Epidemiology Group meeting in Cumbria, England in September. Mark Sherman, M.D. (HREB), spoke on Clinical applications of HPV testing: Today and tomorrow at the New England Society of Pathologists September meeting in Boston and for the Pathology Grand Rounds at the University of Vermont in Burlington in October. While in Boston, Dr. Sherman also gave a visiting professor talk on The pathologist as etiologist: Bridging the chasm between population and laboratory science at the Beth Israel Deaconess Medical Center. In addition, Dr. Sherman has accepted an appointment to serve on the editorial board of Gynecologic Oncology. Rashmi Sinha, Ph.D. (NEB), spoke on Diet and cancer to the Roche Research Chapter of Sigma Xi, the Scientific Research Society, in Nutley, New Jersey in October. Lois B. Travis, M.D., Sc.D. (REB), presented lectures on second cancer primaries at the Sixth International Symposium on Hodgkin Lymphoma in Cologne, Germany in September and at Georgetown Universitys Lombardi Comprehensive Cancer Center, Washington, DC in December. Sophia Wang, Ph.D. (HREB), was an invited speaker and discussant on Genetic markers of cervical cancer risk for the Early Detection Research Network meeting in New York City in September. Mary Ward, Ph.D. (OEEB), gave an invited talk, Agricultural chemicals and cancer: Evidence from occupational and environmental epidemiology studies, at the Cancer Biology Symposium at the University of Colorado at Boulder in November. |
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SPECIMEN MANAGEMENT CONFERENCEJim Vaught, Ph.D., Office of the Director (OD), presented an invited lecture on Specimen management for high throughput genotyping at the International Society of Biological and Environmental Repositories (ISBER) meeting in Perugia, Italy in October. Marianne K. Henderson, M.S., Office of Division Operations and Analysis (ODOA), also gave an invited lecture, Challenges of scientific data management for large epidemiology studies, at the meeting. Dr. Vaught and Ms. Henderson are pictured here with Dr. Robert Hanner, past president of ISBER, in front of Perugias main fountain, which dates from 1278. |
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After more than four years serving as a Visiting Fellow in the Occupational and Environmental Epidemiology Branch (OEEB), Juan Alguacil, M.D., Ph.D., has accepted a position on the faculty of the University of Huelva in Spain. He will be leading the research unit on environmental and occupational epidemiology and teaching epidemiology, preventive medicine, and occupational and environmental health at the medical school. During his stay with the OEEB, Dr. Alguacil made important contributions to the DCEG program, particularly in the areas of pancreatic cancer and bladder cancer epidemiology. Berit
Bakke, Ph.D., a postdoctoral fellow, arrived at the OEEB in October.
Dr. Bakke is an industrial hygienist from the National Institute of
Occupational Health in Oslo. She recently completed her doctoral dissertation
on adverse respiratory effects among construction workers due to exposures
generated by tunneling operations. She will be at DCEG for two years.
Dr. Bakke will be working on several occupational exposure assessment
projects, including case-control and methodologic studies, with Roel
Vermeulen, Ph.D., Joseph Coble, Sc.D., and Patricia Stewart,
Ph.D. Parveen
Bhatti, M.S., has joined the Radiation Epidemiology Branch (REB)
as a predoctoral fellow. Mr. Bhatti graduated with a Master of Science
degree in 2000 from the University of British Columbia in Vancouver
with a major in occupational and environmental hygiene. While at REB,
Mr. Bhatti plans to gain experience in molecular epidemiology in a search
for underlying genetic susceptibility to the carcinogenic effects of
ionizing radiation. He is currently completing his doctoral thesis at
the University of Washington, Seattle, on DNA double strand-break repair
polymorphisms and breast cancer risk. Elizabeth Bluhm, M.D., M.P.H., has joined the REB as a Division of Cancer Prevention (DCP) cancer prevention fellow. Dr. Bluhm received an M.D. from the Mount Sinai School of Medicine, New York City, in 2000. She earned an M.P.H. from the University of North Carolina at Chapel Hill, concentrating in epidemiology. Anil Chaturvedi, Ph.D., has joined the Viral Epidemiology Branch (VEB) as a visiting fellow. In 2004, Dr. Chaturvedi received a Ph.D. in epidemiology from Tulane University School of Public Health and Tropical Medicine in New Orleans. His doctoral dissertation was entitled Prevalence and impact of multiple infections in HIV+ and HIV women. Dr. Chaturvedi will work on a number of VEB studies, with a primary focus on immunologic parameters and genetic polymorphisms related to certain infections and their associated malignancies. Deirdre Hill, Ph.D., who has been a postdoctoral fellow in the REB since 2000, has accepted a position at the University of New Mexico, Albuquerque. During her fellowship at DCEG, Dr. Hill made significant contributions in radiation research. She worked on the risk of glioma, meningioma, and acoustic neuroma associated with diagnostic and therapeutic radiation. Aimee Kreimer, Ph.D., a DCP cancer prevention fellow, has joined the Hormonal and Reproductive Epidemiology Branch (HREB) and is being mentored by Diane Solomon, M.D., and Philip Castle, Ph.D. Dr. Kreimer has an M.S. in health evaluation sciences from the University of Virginia in Charlottesville and a Ph.D. in epidemiology from Johns Hopkins University. She spent last year at the International Agency for Research on Cancer, studying oral HPV and related neoplasias. Dr. Kreimer has continued these studies and is working on HREB cervical cancer projects. DCEG SCIENTISTS TEACH AT GWU Paul Levine, M.D., formerly of VEB and now at George Washington University (GWU), and Roxana Moslehi, Ph.D., Biostatistics Branch (BB), organized and taught a course titled Current Controversies in Cancer Epidemiology at GWUs Department of Public Health and Biostatistics from September to December. Invited speakers included Arthur Schatzkin, M.D., Dr.P.H., Nutritional Epidemiology Branch (NEB), Neil Caporaso, M.D., Genetic Epidemiology Branch (GEB), Michael Leitzmann, M.D., Dr.P.H. (NEB), Eric Engels, M.D., M.P.H. (VEB), and Ruth Pfeiffer, Ph.D. (BB). Wonjin Lee, M.D., a visiting fellow in OEEB, has taken an Associate Professor position at the Department of Preventive Medicine, College of Medicine, Korea University, Seoul. Dr. Lee joined the OEEB in 2001. He worked with several DCEG investigators on studies of stomach and esophageal cancer, lymphoma, multiple myeloma, and lung cancer, as well as exposure to occupational and environmental agents, particularly pesticides. In the Agricultural Health Study, he evaluated the incidence of cancer among pesticide applicators exposed to alachlor and chlorpyrifos. Jolanta Lissowska, Ph.D., has joined HREB for one year as a Guest Scientist under sponsorship by the NCI Office of International Affairs. Dr. Lissowska is a senior epidemiologist at the Cancer Center and Institute of Oncology in Warsaw, Poland. She has been collaborating with DCEG investigators and serving as Principal Investigator on a recently completed multidisciplinary study of breast, ovarian, and endometrial cancers in Poland. During her stay at NCI, she will work with Montserrat Garcia-Closas, M.D., Dr.P.H., Louise Brinton, Ph.D., Mark Sherman, M.D., and others on analyses of data from the study. Panagiota Mitrou, Ph.D., has joined the NEB as a postdoctoral fellow. Dr. Mitrou received her Ph.D. from the University of Cambridge in molecular epidemiology. In addition, Dr. Mitrou holds a bachelors degree in biochemistry and a masters degree in genetics from the University of Sussex, Brighton, United Kingdom. She conducted doctoral research under the supervision of Dr. Sheila Bingham at the Dunn Human Nutrition Laboratory, Cambridge, where she investigated polymorphisms in xenobiotic and folate metabolism genes in relation to colorectal adenoma and cancer risk. She will be working on genetic variation in nutrient metabolism and its impact on cancer risk within the framework of large, epidemiological studies. Diane Solomon, M.D., of the NCI Division of Cancer Prevention (DCP), recently joined HREB as an Adjunct Investigator. Dr. Solomon has collaborated extensively with Mark Schiffman, M.D., M.P.H., Mark Sherman, M.D., and other HREB staff members on cervical cancer studies. Dr. Solomon is the former Chief of the Cytopathology Section in the NCI Laboratory of Pathology. She transferred to DCP to conduct the ASCUS/ LSIL Triage Study, a large randomized trial that established the value of human papillomavirus (HPV) testing to triage equivocal cervical cytology. Dr. Solomon chaired a recent conference that revised the categorization of cervical cytology and an American Cancer Society consensus conference on screening guidelines. Kay Wanke, Ph.D., a cancer prevention fellow, has joined the GEB. Dr. Wanke received her Ph.D. in clinical psychology from Southern Illinois University at Carbondale and an M.P.H. from the Harvard School of Public Health. She is currently leading an analysis of genetic determinants of smoking cessation in heavy smoking men in the Alpha-Tocopheral Beta-Carotene Lung Cancer Prevention Trial. She is also examining the contribution of genetic factors to patterns of behavior in the Polyp Prevention Trial and the relationship of co-morbid psychological conditions to the stages of smoking in NHANES III. Dr. Wankes major interest is in the smoking phenotype. |
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BRUGGE WINS FRANKLIN AWARDDr. Joan S. Brugge, Professor of Cell Biology at Harvard Medical School, received the 4th Annual NCI Rosalind E. Franklin Award for Women in Cancer Research and gave an invited lecture on Probing mechanisms of breast epithelial oncogenesis in a 3D culture model at the 2005 NCI Principal Investigator Retreat. |
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Genetic sequencing technology has come a long way, but unfortunately the computer applications that manage the mounting volumes of data generated have lagged far behind. The current applications are error-prone, because they depend on manual data entry, and their limited visualization capabilities make it difficult for researchers to clearly see what they are looking at. To solve this problem, a team led by Meredith Yeager, Ph.D., at NCIs Core Genotyping Facility (CGF) developed the Genewindow tool for their laboratory. An article announcing Genewindows public availability appeared in the February issue of Nature Genetics (2005;37:109-110). Data that used to take CGF staff days to sift through, enter, and analyze now are handled by an automated system that can feed sequences directly into the CGF databases while also linking to other public databases. CGF staff performs genotyping and DNA sequencing for DCEG and other research groups at NCI, especially the Center for Cancer Research. Over the past year, the CGF has delivered more than four million genotypes to researchers doing genetic analyses. Data that used to take CGF staff days to sift through, enter, and analyze now are handled by an automated system that can feed sequences directly into the CGF databases while also linking to other public databases, such as that of the National Center for Biotechnology Information at the National Library of Medicine. Dr. Yeager explains, We developed this tool in response to problems we were having in databasing and annotating hundreds of genes used in DCEG-based candidate gene studies. We then realized that Genewindow is useful to outside researchers as well. Researchers from a variety of institutions, such as universities, cancer centers, biotechnology companies, and other institutes and agencies, have visited the Genewindow site (http://genewindow.nci.nih.gov) to explore it as a reference tool. Genewindows strength comes not only from its automation and ability to cut workload, but also in its visualization capabilities. It clearly delineates each gene along with its associated data so that a scientist can easily tell which parts of the gene code for a protein, what variations have been found, and how these variations affect protein structure. Bernice Packer, M.S., manager of bioinformatics at the CGF, compares Genewindow to a land map. Just as a map might display the cities in each country, Genewindow displays publicly known genetic polymorphisms as marked regions along the human genome. Like a cartographer who might add pushpins to a land map when new cities are established, CGF staff adds their own annotations in Genewindow when they find new polymorphisms. Genewindow also contains a legend, complete with diagrams and explanations. The CGF bioinformatics team has designed the tool to be as intuitive, user-friendly, and helpful as possible. They are constantly adding new features to Genewindows repertoire. In the works are the incorporation of haplotypes and haplotype tag single nucleotide polymorphisms (htSNPs) and the option to filter information from selected databases. The developers also plan to release the source code so that other laboratories can not only use Genewindow as a reference, but incorporate it into their own operations for data analysis. Cari Kornblit |
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