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NCI’s Division of Cancer Epidemiology and Genetics Neil Caporaso, M.D. Chief, Genetic Epidemiology Branch DCEG, NCI www.dceg.cancer.gov Division of Cancer Epidemiology and Genetics Discovering the Causes of Cancer national and international intramural, population-based research Mission: * broad-based, high quality, high impact research to uncover causes of cancer and means of its prevention. * national and international perspective. * develop research resources and strategic partnerships in molecular epidemiology across NCI, NIH and the research global community * train the next generation of scientists in cancer epidemiology and related areas. National Cancer Institute Intramural Divisions DCEG 8 Branches/1 Lab 69 Principal Investigators Extramural Divisions CCR ~205 Investigators National Cancer Institute (NCI) Division of Cancer Epidemiology and Genetics Find the CAUSE! Genetic Epidemiology Branch Other Branches focus on Nutrition, Hormones, Infection, Occupation, Statistics, Radiation Why have an intramural program? Example 1 In the 1980/90s many groups independently reported that normal patients had excess clonal B lymphocytes in the blood. Each investigator gave it a different name Benign monoclonal B-cell lymphocytosis (BMBCL) Idiopathic persistent lymphocytosis B-monoclonal lymphocytosis undetermined significance Smoldering CLL B-cell monoclonal lymphocytosis (BCML) Sub-clinical BCLL B-cell monoclonal lymphocytosis CD5 negative BMLUS CLL-like immunophenotype (CLUS) Han 1984 Bassan 1988 Garcia 1989 Montserrat 1988 Marti 1993 Maiese 1997 Wang 2002 Rawstron 2 Why have an intramural program? 2 2003 2005 2007 2010 Monoclonal B Cell Lymphocytosis (MBL) Example 2 Family Studies were not popular Early ideas in human genetics: If it’s genetic it’s rare If its genetic it’s only in families If it’s genetic you can’t change it If it’s genetic there is no treatment If it’s genetic the environment doesn’t matter ALL THESE ASSUMPTIONS WERE WRONG Family studies by our group….. Family studies by our group….. dysplastic nevus Most Cancer is due to the Environment Dramatic differences in cancer rates by geography and over time are only compatible with extrinsic environmental causes Established by a vast body of descriptive, ecological, and analytical epidemiology Per-Capita Consumption of Different Forms of Tobacco in The U.S. 1880-2003 Pounds of Tobacco Per-Capita 14 Cigarettes Cigars Pipe/roll your own Chewing Snuff 12 10 8 6 4 Snuff Chewing Pipe/roll your own Cigarettes Cigars 2 0 1880 1890 1900 1910 Decades 1920 1930 in the1940 1900s1950 1960 1970 1980 1990 2000 Year Data Source USDA Lung cancer rate drops after smoking cessation Relative Risks of Lung Cancer According to Years Since Quitting Smoking among Males in Three Cohort Studies of Smokers 20 18 16 Relative Risk 14 12 10 8 6 4 2 0 0 1-4 5-9 10-14 15-19 Years Since Quitting Smoking British Physicians U.S. Veterans American Cancer Society 20+ Why here? Copper Smelter, Montana Traditional epidemiology E Exposure Tobacco D Disease Lung Cancer Molecular epidemiology G E exposure ID EBE ASF ED D internal dose early biological effect altered structure or function early disease disease Adding biomarkers allows us to investigate genes and mechanisms Integrative epidemiology G B E ID EBE ASF ED D O exposure internal dose early biological effect altered structure or function early disease disease Behavior Outcome DCEG Areas of Investigation • Lifestyle risk factors (hormonal and nutritional exposures) • Environmental and occupational exposures • Infectious agents • Radiation • Statistics and methods development • Genetic predisposition • Genome-wide association studies and Next-gen sequencing DCEG Staff and Trainee Profile ~25 summer students ~100 postbaccalaureate, predoctoral, postdoctoral and clinical trainees 36 staff scientist/staff clinicians 26 tenure-track investigators 43 senior investigators DCEG Selected Discoveries Hormone replacement and breast/ovarian cancer Benzene and formaldehyde and leukemia/lymphoma Role of p53 gene in Li-Fraumeni syndrome Gail breast cancer risk model Cancer risk among atomic bomb survivors No link between breast implants – breast cancer, cell phones – brain cancer, or power-lines – childhood leukemia Personal view- Our Branch Selected Discoveries (GEB/2014) Largest study of genes and lung cancer POT1- gene associated with familial melanoma Methylome and lung cancer The “Time to First Cigarette” is a critical determinant of lung cancer risk DCEG What we look for in early career investigators • Great science: important work, published in top-notch journals • Good quality work: strong rationale and research methods • Depth and breath of scientific knowledge • Evidence of creativity, innovation, and originality – person is moving the field forward • Collaborative, interdisciplinary spirit • Capacity for independence and leadership • Ability and enthusiasm to mentor Personal view What we look for in early career investigators 3 qualities TRAINING MOVIVATION and CHARACTER HARD WORK