NCI Gene-Environment Think-Tank


Overview

Risk of cancer is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with cancer. However, it remains unclear how to best incorporate gene-environment interplay into study design and analysis in order to better understand cancer etiology, or to identify public health interventions.

NCI's Epidemiology and Genomics Research Program (EGRP) sponsored a Gene-Environment Think-Tank on January 10-11, 2012 in Rockville, MD.

The objective was to facilitate discussions on the:

  1. goals of gene-environment interaction studies in cancer epidemiology;
  2. state of the science of gene-environment interactions; and
  3. opportunities for the future, including novel study design and analysis tools.

Topics covered included presentations on summary results from large consortia studies of breast, lung, colon, and bladder cancer; review of current statistical methods; and discussion of challenges in the field. The Think-Tank expanded on earlier discussions about gene-environment interactions made at the September 2010 Workshop on Next-Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases.

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Agenda

View Agenda for Day 1 of the Think Tank
January 10 Topic
12:30 p.m. Welcome
Muin Khoury, M.D., Ph.D.
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences (DCCPS)
National Cancer Institute (NCI)
12:35 p.m. Introduction to Meeting
Leah Mechanic, Ph.D., M.P.H.
Host Susceptibility Factors Branch
Epidemiology and Genomics Research Program, DCCPS, NCI
12:45 p.m. Goals of Gene-Environment Interaction Studies in Cancer Epidemiology
Nilanjan Chatterjee, Ph.D.
Division of Cancer Epidemiology and Genetics, NCI
1:00 p.m. State of the Science - Short Presentations
  • What has been learned from studies of recognized gene-environment interactions? Have epidemiologic studies used gene-environment interaction to uncover new loci, modifiable risk factors, or biological insights into cancer etiology and outcomes? (i.e., What has been found? What are current strategies? What are alternate strategies for the future?)
  • Are we asking the right questions?
1:00 p.m. Breast Cancer
Peter Kraft, Ph.D.
Harvard School of Public Health
1:20 p.m. Colorectal Cancer
Ulrike Peters, Ph.D.
Fred Hutchinson Cancer Research Center
1:40 p.m. Lung Cancer
Christopher Amos, Ph.D.
The University of Texas MD Anderson Cancer Center
2:00 p.m. Bladder Cancer
Nathaniel Rothman, M.D., M.P.H., M.H.S.
Division of Cancer Epidemiology and Genetics, NCI
2:20 p.m. Glioma
Melissa Bondy, Ph.D.
Baylor College of Medicine
2:40 p.m. Knowledge Management and Synthesis
Paolo Boffetta, Ph.D.
The Mount Sinai Hospital
3:20 p.m. Group Discussion: State of the Science
  • Discussion expanding upon presented data, data not presented, and other cancer types

Panel:
Peter Kraft, Ph.D., Harvard School of Public Health
Ulrike Peters, Ph.D., Fred Hutchinson Cancer Research Center
Christopher Amos, Ph.D., MD Anderson Cancer Center
Nathaniel Rothman, M.D., M.P.H., M.H.S., Division of Cancer Epidemiology and Genetics, NCI
Melissa Bondy, Ph.D., Baylor College of Medicine
Paolo Boffetta, Ph.D., The Mount Sinai Hospital

Moderator:
Elizabeth Gillanders, Ph.D., Host Susceptibility Factors Branch, Epidemiology and Genomics Research Program, DCCPS, NCI

Facilitators:
Naoko Simonds, Sc.D., Clinical and Translational Epidemiology Branch, Epidemiology and Genomics Research Program, DCCPS, NCI
Carolyn Hutter, Ph.D., Fred Hutchinson Cancer Research Center

4:20 p.m. Methodological Challenges and Opportunities - Analytical Methods
4:20 p.m. Emerging Approaches for Gene-Environment Wide Association Studies
Duncan Thomas, Ph.D.
Keck School of Medicine of the University of Southern California
4:40 p.m. Beyond Logistic Regression and Case-Only Tests
Clarice Weinberg, Ph.D.
National Institute of Environmental Health Sciences
5:00 p.m. Group Discussion: Analytical Methods

Panel
Duncan Thomas, Ph.D., Keck School of Medicine
Clarice Weinberg, Ph.D., National Institute of Environmental Health Sciences
Peter Kraft, Ph.D., Harvard School of Public Health

Moderator:
Nilanjan Chatterjee, Ph.D., Division of Cancer Epidemiology and Genetics, NCI

Facilitators:
Kimberly McAllister, Ph.D., National Institute of Environmental Health Sciences
Jim Gauderman, Ph.D., University of Southern California


View Agenda for Day 2 of the Think Tank
January 11 Topic
8:00 a.m. Introduction to Day 2
Leah Mechanic, Ph.D., M.P.H.
Host Susceptibility Factors Branch
Epidemiology and Genomics Research Program, DCCPS, NCI
8:10 a.m. Methodological Challenges and Opportunities - Measurement or Assessment of the Environment
8:10 a.m. Exposure Measurement Error in Complex Studies, Some Basic Principles and Relevant Examples
Daniel O. Stram, Ph.D.
Keck School of Medicine of the University of Southern California
8:30 a.m. Challenges of Exposure Assessment and Measurement Error in Studies of GxE Interaction
Donna Spiegelman, Ph.D.
Harvard School of Public Health
8:50 a.m. Novel Methodologies for Exposure Assessment - Report from Genes Environment and Health Initiative (GEI) Exposure Biology Program
David Balshaw, Ph.D.
National Institute of Environmental Health Sciences
9:10 a.m. Time Varying Exposure Metrics and Timing of Exposure Effects
Molin Wang, Ph.D.
Harvard School of Public Health
9:50 a.m. Group Discussion: Measurement or Assessment of the Environment

Panel:
Daniel O. Stram, Ph.D., Keck School of Medicine
Donna Spiegelman, Ph.D., Harvard School of Public Health
David Balshaw, Ph.D., National Institute of Environmental Health Sciences
Molin Wang, Ph.D., Harvard School of Public Health

Moderator:
Kimberly McAllister, Ph.D., National Institute of Environmental Health Sciences

Facilitators:
Gary Ellison, Ph.D., Modifiable Risk Factors Branch, Epidemiology and Genomics Research Program, DCCPS, NCI
Daniel Shaughnessy, Ph.D., National Institute of Environmental Health Sciences

10:50 a.m. Methodological Challenges and Opportunities - Study Designs and Approaches
11:10 a.m. Opportunities for Study in Diverse Populations
Christian Abnet, Ph.D.
Division of Cancer Epidemiology and Genetics, NCI
11:30 a.m. Epigenetics Studies for Gene-Environment
Margaret Daniele Fallin, Ph.D.
The Johns Hopkins University
11:50 a.m. Opportunities for Study of Gene-Environment in Cancer
Laura Jean Bierut, M.D.
Washington University
1:10 p.m. Group Discussion: Study Designs and Approaches

Panel:
Christian Abnet, Ph.D., Division of Cancer Epidemiology and Genetics, NCI
Margaret Daniele Fallin, Ph.D., The Johns Hopkins University
Laura Jean Bierut, M.D., Washington University

Moderator:
Nancy Cox, Ph.D., University of Chicago

Facilitators:
Jill Reedy, Ph.D., Applied Research Program
Sheri Schully, Ph.D., Host Susceptibility Factors Branch, Epidemiology and Genomics Research Program, DCCPS, NCI

2:10 p.m. Clinical and Public Health Implications
2:10 p.m. Application of GxE to Cancer Prevention Studies
Ross Prentice, Ph.D.
Fred Hutchinson Cancer Research Center
3:00 p.m. Group Discussion: Discussion and Meeting Summation
  • Overview and discussion of controversial issues raised during course of meeting
  • Where do we go from here?

Panel:
Nilanjan Chatterjee, Ph.D., Division of Cancer Epidemiology and Genetics, NCI
Margaret Daniele Fallin, Ph.D., The Johns Hopkins University
Peter Kraft, Ph.D., Harvard School of Public Health
Nathaniel Rothman, M.D., M.P.H., M.H.S., Division of Cancer Epidemiology and Genetics, NCI
John Witte, Ph.D., University of California, San Francisco

Moderator:
Stephen Chanock, M.D., Division of Cancer Epidemiology and Genetics, NCI

4:00 p.m. Group Discussion: Meeting Conclusions
  • What can NCI and NIH do to facilitate research in genes and environment?

Moderator:
Peter Kraft, Ph.D., Harvard School of Public Health

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Workshop Summary

Hutter CM, Mechanic LE, Chatterjee N, Kraft P, Gillanders EM, on behalf of NCI Gene-Environment Think Tank. Gene-Environment Interactions in Cancer Epidemiology: A National Cancer Institute Think Tank ReportExternal Web Site Policy. Genet Epidemiol. 2013 Nov;37(7):643-657. [Epub 2013 Oct 5]

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Additional Resources

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Related Funding Opportunities

A related NIH Funding Opportunity Announcement (FOA), Methods and Approaches for Detection of Gene-Environment InteractionsExternal Web Site Policy (PAR-11-032), was announced in November 2010; applications were due February 2011.

EGRP does not currently have any gene-environment interaction FOAs, but encourages investigator-initiated grant applications on the topic.

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Contact

For further information or questions about the Think-Tank, contact Leah Mechanic, Ph.D., M.P.H., Program Director, Host Susceptibility Factors Branch, Epidemiology and Genomics Research Program.

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