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Gene-Environment Interactions in Cancer Epidemiology: A National Cancer Institute Think Tank Report

Authors

  • Carolyn M. Hutter,

    Corresponding author
    1. Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
    • Correspondence to: Carolyn M. Hutter, Host Susceptibility Factors Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Room 4E232, MSC 9763, Bethesda 20892-7393, MD, USA. E-mail: huttercm@mail.nih.gov

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    • These authors contributed equally to this paper and both are first authors.

  • Leah E. Mechanic,

    1. Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
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    • These authors contributed equally to this paper and both are first authors.

  • Nilanjan Chatterjee,

    1. Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
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    • These authors contributed equally to this paper and all are senior authors.

  • Peter Kraft,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
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    • These authors contributed equally to this paper and all are senior authors.

  • Elizabeth M. Gillanders,

    1. Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
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    • These authors contributed equally to this paper and all are senior authors.

  • on behalf of the NCI Gene-Environment Think Tank

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    • The NCI Think Tank participants are as follows (*speakers, panelists, and discussion moderators): *Christian C. Abnet, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, Bethesda, MD, USA; *Christopher Amos, Dartmouth-Hitchcock Norris Cotton Cancer Center, Community and Family Medicine, Hanover, NH, USA; *David Balshaw, National Institute of Environmental Health Sciences, Center for Risk & Integrated Sciences, Research Triangle Park, NC, USA; Heike Bickeböller, University of Göttingen, Department of Genetic Epidemiology, Gottingen, Germany; *Laura Jean Bierut, Washington University, Department of Psychiatry, St. Louis, MO, USA; *Paolo Boffetta, Mount Sinai School of Medicine, Institute for Translational Epidemiology, New York, NY, USA; *Melissa Bondy, Baylor College of Medicine, Department of Pediatrics Hematology and Oncology Division, Houston, TX, USA; *Stephen Chanock, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA; *Nilanjan Chatterjee, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Biostatistics Branch, Bethesda, MD, USA; Huann-Sheng Chen, National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Bethesda, MD, USA; *Nancy Cox, University of Chicago, Department of Medicine, Chicago, IL, USA; Immaculata De Vivo, Harvard School of Public Health, Department of Epidemiology, Boston, MA, USA; Rao Divi, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Josee Dupuis, Boston University School of Public Health, Department of Biostatistics, Boston, MA, USA; Gary Ellison, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; *Margaret Daniele Fallin, Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA; W. James Gauderman, Keck School of Medicine of University of Southern California, Department of Preventive Medicine, Los Angeles, CA, USA; *Elizabeth Gillanders, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Christopher Haiman, Keck School of Medicine of University of Southern California, Department of Preventive Medicine, Los Angeles, CA, USA; Carolyn Hutter, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Naoko Ishibe Simonds, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Edwin Iversen, Duke University, Department of Statistical Science, Durham, NC, USA; *Muin J. Khoury, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; *Peter Kraft, Harvard School of Public Health, Department of Epidemiology and Biostatistics, Boston, MA, USA; Loic Le Marchand, University of Hawaii Cancer Center, Epidemiology Program, Honolulu, HI, USA; Dongxin Lin, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Molecular Oncology, Beijing, China; *Kimberly McAllister, National Institute of Environmental Health Sciences, Division of Extramural Research and Training, Susceptibility & Population Health Branch, Research Triangle Park, NC, USA; *Leah Mechanic, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; *Ulrike Peters, Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA; *Ross Prentice, Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA, USA; Timothy Rebbeck, University of Pennsylvania, Department of Biostatistics and Epidemiology, Philadelphia, PA, USA; Jill Reedy, National Cancer Institute, Division of Cancer Control and Population Sciences, Applied Research Program, Bethesda, MD, USA; *Nathaniel Rothman, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, Bethesda, MD, USA; Sheri Schully, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Daniela Seminara, National Cancer Institute, Division of Cancer Control and Population Sciences, Epidemiology and Genomics Research Program, Bethesda, MD, USA; Daniel Shaughnessy, National Institute of Environmental Health Sciences, Division of Extramural Research and Training, Susceptibility & Population Health Branch, Research Triangle Park, NC, USA; Sanjay Shete, MD Anderson Cancer Center, Program in Biomathematics and Biostatistics, Houston, TX, USA; *Donna Spiegelman, Harvard School of Public Health, Departments of Epidemiology and Biostatistics, Boston, MA, USA; *Daniel O. Stram, Keck School of Medicine of University of Southern California, Department of Preventive Medicine, Los Angeles, CA, USA; *Duncan Thomas, Keck School of Medicine of University of Southern California, Department of Preventive Medicine, Los Angeles, CA, USA; *Molin Wang, Harvard School of Public Health, Department of Epidemiology and Biostatistics, Boston, MA, USA; Wendy Wang, National Cancer Institute, Division of Cancer Prevention, Bethesda, MD, USA; *Clarice Weinberg, National Institute of Environmental Health Sciences, Intramural Research Division, Biostatistics Branch, Research Triangle Park, NC, USA; Deborah M. Winn, National Cancer Institute, Division of Cancer Control and Population Sciences, Bethesda, MD, USA; *John S. Witte, University of California, San Francisco, Department of Epidemiology and Biostatistics, San Francisco, CA, USA


ABSTRACT

Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 < MAF < 0.05) genetic variants associated with cancer. The marginal effects of most of these variants have been small (odds ratios: 1.1–1.4). There remain unanswered questions on how best to incorporate the joint effects of genes and environment, including gene-environment (G × E) interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a “Gene-Environment Think Tank” on January 10–11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors.

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