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Review of the Gene‐Environment Interaction Literature in Cancer: What Do We Know?
Author(s) -
Simonds Naoko I.,
Ghazarian Armen A.,
Pimentel Camilla B.,
Schully Sheri D.,
Ellison Gary L.,
Gillanders Elizabeth M.,
Mechanic Leah E.
Publication year - 2016
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21967
Subject(s) - pharmacogenomics , colorectal cancer , cancer , genome wide association study , breast cancer , medicine , bioinformatics , biology , genetics , gene , genotype , single nucleotide polymorphism
Background Risk of cancer is determined by a complex interplay of genetic and environmental factors. Although the study of gene‐environment interactions (G×E) has been an active area of research, little is reported about the known findings in the literature. Methods To examine the state of the science in G×E research in cancer, we performed a systematic review of published literature using gene‐environment or pharmacogenomic flags from two curated databases of genetic association studies, the Human Genome Epidemiology (HuGE) literature finder and Cancer Genome‐Wide Association and Meta Analyses Database (CancerGAMAdb), from January 1, 2001, to January 31, 2011. A supplemental search using HuGE was conducted for articles published from February 1, 2011, to April 11, 2013. A 25% sample of the supplemental publications was reviewed. Results A total of 3,019 articles were identified in the original search. From these articles, 243 articles were determined to be relevant based on inclusion criteria (more than 3,500 interactions). From the supplemental search (1,400 articles identified), 29 additional relevant articles (1,370 interactions) were included. The majority of publications in both searches examined G×E in colon, rectal, or colorectal; breast; or lung cancer. Specific interactions examined most frequently included environmental factors categorized as energy balance (e.g., body mass index, diet), exogenous (e.g., oral contraceptives) and endogenous hormones (e.g., menopausal status), chemical environment (e.g., grilled meats), and lifestyle (e.g., smoking, alcohol intake). In both searches, the majority of interactions examined were using loci from candidate genes studies and none of the studies were genome‐wide interaction studies (GEWIS). The most commonly reported measure was the interaction P ‐value, of which a sizable number of P ‐values were considered statistically significant (i.e., <0.05). In addition, the magnitude of interactions reported was modest. Conclusion Observations of published literature suggest that opportunity exists for increased sample size in G×E research, including GWAS‐identified loci in G×E studies, exploring more GWAS approaches in G×E such as GEWIS, and improving the reporting of G×E findings.