Gene-environment interactions in cancer epidemiology: A national cancer institute think tank report

Carolyn M. Hutter, Leah E. Mechanic, Nilanjan Chatterjee, Peter Kraft, Elizabeth M. Gillanders, Christian C. Abnet, Christopher Amos, David Balshaw, Heike Bickeböller, Laura Jean Bierut, Paolo Boffetta, Melissa Bondy, Stephen Chanock, Huann Sheng Chen, Nancy Cox, Immaculata De Vivo, Rao Divi, Josee Dupuis, Gary Ellison, Margaret Daniele FallinW. James Gauderman, Elizabeth Gillanders, Christopher Haiman, Carolyn Hutter, Naoko Ishibe Simonds, Edwin Iversen, Muin J. Khoury, Loic Le Marchand, Kimberly McAllister, Leah Mechanic, Ulrike Peters, Ross Prentice, Timothy Rebbeck, Jill Reedy, Nathaniel Rothman, Sheri Schully, Daniela Seminara, Daniel Shaughnessy, Sanjay Shete, Donna Spiegelman, Daniel O. Stram, Duncan Thomas, Molin Wang, Wendy Wang, Clarice Weinberg, Deborah M. Winn, John S. Witte

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)643-657
Number of pages15
JournalGenetic epidemiology
Volume37
Issue number7
DOIs
StatePublished - Nov 2013

Keywords

  • Complex phenotypes
  • Gene-environment interactions
  • Genetic epidemiology

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)

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