Recommendations and proposed guidelines for assessing the cumulative evidence on joint effects of genes and environments on cancer occurrence in humans
Open accessAbstract
We propose guidelines to evaluate the cumulative evidence of gene-environment (G × E) interactions in the causation of human cancer. Our approach has its roots in the HuGENet and IARC Monographs evaluation processes for genetic and environmental risk factors, respectively, and can be applied to common chronic diseases other than cancer. We first review issues of definitions of G × E interactions, discovery and modelling methods for G × E interactions, and issues in systematic reviews of evidence for G × E interactions, since these form the foundation for appraising the credibility of evidence in this contentious field. We then propose guidelines that include four steps: (i) score the strength of the evidence for main effects of the (a) environmental exposure and (b) genetic variant; (ii) establish a prior score category and decide on the pattern of interaction to be expected; (iii) score the strength of the evidence for interaction between the environmental exposure and the genetic variant; and (iv) examine the overall plausibility of interaction by combining the prior score and the strength of the evidence and interpret results. We finally apply the scheme to the interaction between NAT2 polymorphism and tobacco smoking in determining bladder cancer risk.
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A few reports have addressed some of these statistical aspects but were mainly intended for an epidemiological audience.
“To date, a few reports 8,9 have addressed some of these aspects but they were mainly intended for an epidemiological audience.”
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- Authors
- Boffetta, P., Winn, D. M., Ioannidis, J. P., Thomas, D. C., Little, J., Smith, G. D., Cogliano, V. J., Hecht, S. S., Seminara, D., Vineis, P., & Khoury, M. J.
- Affiliations
- Tisch Cancer Institute (US)
- National Institutes of Health (US)
- University of Southern California (US)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Boffetta, P.
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-16
- Volume
- 41
- Issue
- 3
- Pages
- 686-704
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- PMC
- PMC3481885
- OpenAlex
- W2146841033
- Cited by
- 48
- References
- 118
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 11 · 2012: 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Epidemiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (R01ES019876)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- gene-environment interaction, cancer risk, systematic reviews, genetic variants, environmental exposure, NAT2 polymorphism, smoking, bladder cancer, interaction modeling
- MeSH terms
- Arylamine N-Acetyltransferase, Urinary Bladder Neoplasms, Data Interpretation, Statistical, Humans, Models, Theoretical, Neoplasms, Research Design, Smoking, Practice Guidelines as Topic, Gene-Environment Interaction
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