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Dr. Deborah M. Winn, Associate Director (Acting), Epidemiology and Genetics Research Program
These are exciting times for those of us in the field of cancer epidemiology, and a thrilling time to be at the National Cancer Institute (NCI). Major shifts are occurring in how epidemiologists work together and with the greater scientific community, the types of scientific questions they are asking, the technical approaches they are using to answer fundamental questions of cancer etiology, and the uses to which epidemiology is being put. These remarkable changes are likely to yield new insights into causes of cancer and potential applications to prevent and ameliorate the consequences of cancer.
The Epidemiology and Genetics Research Program (EGRP) is the largest funder of cancer epidemiology grants nationally and worldwide, with support provided to U.S. and international investigators. Supported investigators undertake studies to understand the determinants of cancer occurrence and health outcomes, including behavioral, environmental, infectious, medical, and social and cultural factors and life events and experiences that have a health impact, as well as genetic factors and other personal susceptibility factors.
Findings from EGRP-supported studies can lead to the development of interventions and approaches to prevent cancer, detect it earlier, and reduce morbidity and mortality from the disease. Epidemiologic findings are critical to NCI’s goals because they generate important hypotheses that can be tested in experimental studies in animals and humans; improve cancer risk assessment; lead to improved prevention, diagnosis, and treatment of cancer; and reduce morbidity and mortality after a cancer diagnosis.
An important role of EGRP is to advance the field of cancer epidemiology. Staff are developing research agendas in areas such as public health genomics, genetic epidemiology, epigenetics, pharmacoepidemiology and pharmacogenomics, and racial/ethnic disparities in cancer susceptibility. New funding initiatives are being created in high-priority research areas, including extension of genome-wide association studies (GWAS) to new phenotypes, analyses, technologies, and populations; risk prediction modeling; and energy-balance. Our staff work directly with individual grant applicants and grantees by advising them on grantsmanship issues from the presubmission stage through the end of the grant, including identification of appropriate funding mechanisms and NCI and EGRP scientific priorities. Staff also monitor scientific progress offering advice, if needed, and ensuring a strong return on NCI’s investment.
EGRP also plays a key role in building and supporting research infrastructures and resources through the facilitation and funding of cancer epidemiology research consortia and cohorts. Epidemiologists increasingly are aware of the importance of achieving sample sizes that are often beyond the size of any given study and now frequently are using existing scientific consortia or creating new ones to address scientific questions in cancer epidemiology. These consortia jointly pool data from their studies to enable analyses of data and biospecimens using larger numbers of study participants than would be possible with any single investigator’s study. Consortia are comprised of investigators who are engaged in case-control studies of a particular tumor type, or who are responsible for large population cohorts, and/or who are studying high-risk families to understand genetic factors in cancer etiology. EGRP develops and encourages the formation of consortia in many different ways, including serving on steering committees that govern these collaborative teams, providing advice on best practices, guidance on obtaining funding, and meeting support. Additionally, staff assist investigators leverage their research resources by providing data-sharing infrastructures.
GWAS hold promise for greatly advancing our understanding of the etiology of cancer. They are studies of genetic variation across the entire genome designed to identify genetic associations with cancer. These studies examine differences between people with cancer and control groups of people without cancer at hundreds of thousands of points across the genome. GWAS have generated a wealth of data, and a challenge now is to follow up these clues with rigorous and efficient investigations on genomic variants to establish with confidence the significance of these variants in cancer susceptibility. To this end, EGRP is supporting transdisciplinary research projects designed to take advantage of existing cancer GWAS by exploiting previously generated “initial scan” GWAS data and to accelerate and coordinate integrative post-GWAS discovery research. Other enormous challenges exist in the design, validation, and analyses of GWAS, and EGRP is providing funding and helping to foster interchange among investigators to address them.
EGRP also strives to expand the type of scientific questions being asked in epidemiologic studies based on new discoveries in basic sciences. For example, EGRP and the National Institute of Environmental Health Sciences (NIEHS) cofund the Breast Cancer and Environment Research Program (BCERP) to study environmental exposures that may predispose a woman to breast cancer throughout her life. Two coordinated efforts are underway to examine the fundamental hypothesis that increased exposure to estrogens and estrogen-like compounds during a woman’s lifetime increases her risk of breast cancer. The first effort is an epidemiologic study of ethnically diverse cohorts of young girls that aims to examine the onset of breast development, age at menarche, and the pubertal time course, as well as factors affecting these transitions, such as exposures to chemical agents, diet, exercise, obesity, family medical history, psychosocial stressors, and markers of genetic susceptibility.
In parallel, BCERP is conducting animal studies to characterize the molecular features of the mammary gland and determine how exposure to potential carcinogens during critical times in the life cycle influences cancer risk. While the focus of the human studies is on the pre-pubertal and pubertal stage of the lifespan, the animal studies allow us to consider environmental and other influences over the lifespan, including mammary carcinogenesis. BCERP works in partnership with advocacy groups to add their insight and experience to the research effort, leverage expertise in outreach activities, and help translate research results into improved understanding and prevention of breast cancer. The ultimate goal is to discover possible environmental causes of breast cancer in order to protect future generations from this disease.
Scientific partnerships are fostered across NCI, the National Institutes of Health (NIH), and with other federal and international cancer research agencies. EGRP works extensively with epidemiologists and scientists in other disciplines in the Division of Cancer Epidemiology and Genetics (DCEG), which is NCI’s intramural epidemiology research arm, and elsewhere across the NIH. It makes contributions to the Institutes through service on key committees and working groups, such as committees concerned with data sharing and biospecimen repositories; the Trans-NCI Human Genomics Coordinating Committee; the Trans-NCI Pharmacoepidemiology and Pharmacogenomics Working Group; the NIH Roadmap Initiative on Epigenetics; and other trans-NIH initiatives, such as the Genes, Environment, and Health Initiative (GEI) and research on climate change. Building and sustaining these relationships promotes transdisciplinary approaches that synergize scientific discovery.
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