Gene-Environment Research and Cancer Epidemiology

A pair of hands holding puzzle pieces representing the different parts of Gene Environment research.

Image courtesy of the National Institute
of Environmental Health Sciences (NIEHS)


Risk of most cancer types are determined by a complex interplay of genetic and environmental factors. Recent studies provide theoretical and empirical evidence that additional genetic and environmental factors can be identified in studies that examine gene-environment (GxE) interactions. More importantly, GxE interaction research has the potential to facilitate insights into biological mechanisms and strategies for cancer prevention and control. Despite progress, several challenges remain for performing these studies. These challenges stem, in part, from the complex, evolving, and expanding nature of the genetic and environmental data collected.

The Epidemiology and Genomics Research Program (EGRP), at the National Cancer Institute's (NCI) Division of Cancer Control and Population Sciences (DCCPS), supports extramural research that investigates both genetic and environmental factors that may contribute to the etiology of cancer and/or impact cancer outcomes.

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Funding Opportunities

NCI-sponsored Funding Opportunity Announcements (FOAs) related to gene – environment interactions include:

  • Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes – expires May 8, 2020, unless reissued
  • Secondary Analyses of Alcohol and Chronic Disease – expires September 8, 2019, unless reissued
  • Exploratory Grants in Cancer Epidemiology and Genomics Research – expires May 8, 2019, unless reissued

EGRP also encourages investigator-initiated grant applications on this topic.

EGRP joins with other NCI Divisions, Offices, and Centers and other Institutes and Centers at the National Institutes of Health (NIH) to fund grant applications submitted in response to FOAs.

View the full list of epidemiology and genomics research FOAs.

The National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) also sponsor FOAs related to gene-environment research.

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Research Resources

Resources and tools specific to GxE research, or which provide specific modules for GxE studies, and analysis are listed below.

Analytical Tools
  • Bayesian model for Detecting Gene-Environment Interactions (BaDGE)
    This webpage, from NCI's intramural Division of Cancer Epidemiology and Genetics (DCEG), contains an R package implementing the Bayeisan model for detecting gene environment interaction.
  • Case-control Genetics (CGEN)
    Case-control Genetics (CGEN), from NCI's DCEG, is an R package for analyzing genetic data on case-control samples, with particular emphasis on novel methods for detecting Gene-Gene and Gene-Environment interactions.
  • GXEscanExternal Web Site Policy
    This program, out of the University of Southern California, detects GxE interactions in a genome-wide association study by implementing a suite of testing methods for GEWIS data, including efficient two-step methods.
  • METALExternal Web Site Policy
    This program, from the University of Michigan, performs meta-analysis of SNPxEnvionrment interaction and is a common package for combining existing GWAS results.
  • MultAssoc
    This MATLAB software package, from NCI's DCEG, tests association of a disease with a group of SNPs after accounting for their interaction with another group of SNPs or environmental exposures.
  • PLINKExternal Web Site Policy
    This program is a free, open-source whole genome association analysis toolset, designed to perform a range of basic, large-scale analyses in a computationally efficient manner. This program was developed by the Center for Human Genetic Research (CHGR), Massachusetts General Hospital (MGH), and the Broad Institute of Harvard & MIT. Tests for GxE may be performed in PLINK.
  • ProbABELExternal Web Site Policy
    This program is designed to perform association analysis by mean of regression of the outcome of interest onto estimated genotypic probabilities in a fast, memory-efficient and, consequently, genome-wide feasible manner and may be used to test for GxE. This tool is from

Programs and Macros for Estimating Power
  • GEmis2External Web Site Policy
    This SAS macro, a product of the Harvard School of Public Health, can be used for power calculations for gene-environment tests incorporating misclassified exposures.
  • Power
    This windows-based program, from NCI's DCEG, computes sample size and power for binary outcome studies (case-control and cohort studies) based on a logistic-live regression model with one covariate or two covariates (e.g., gene X exposure interactions).
  • QuantoExternal Web Site Policy
    This software's specific uses include: power calculations, GxE and joint test, case-control, case-only, family-based designs, continuous outcome. This software is a product of the University of Southern California.
  • Stata Programs for Estimation of Study PowerExternal Web Site Policy
    These programs, out of Cancer Research UK, can be used for power calculations as well as GxE testing from logistic regression.

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Selected EGRP GxE Publications

A workshop held on October 17-18, 2014 by NCI and the National Institute of Environmental Health Sciences (NIEHS), in conjunction with the annual American Society of Human Genetics meeting, explored new approaches and tools developed in recent years for GxE interaction discovery. Following this workshop, a group of participants collaborated to develop a series of scientific manuscripts that will highlight current and critical issues and themes in GxE research that need additional consideration, including the topics of improved data analytical methods, environmental exposure assessment, and incorporation of functional data and annotations.

Some additional GxE publications by EGRP and other authors follows:

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EGRP co-sponsors workshops and meetings to convene experts in the fields of cancer epidemiology and environmental research to review the state-of-the-science, identify research gaps, and establish scientific agendas/priorities for the future, such as:

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For general questions about EGRP's interests in gene-environment research, contact Leah Mechanic, Ph.D., M.P.H.

For questions about the following aspects of GxE research, contacts include:

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