{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:01:27Z","timestamp":1791266487938,"version":"4.1.0"},"reference-count":89,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T00:00:00Z","timestamp":1459987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Risk of cancer is determined by a complex interplay of genetic and environmental factors. Although the study of gene\u2010environment interactions (G\u00d7E) has been an active area of research, little is reported about the known findings in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To examine the state of the science in G\u00d7E research in cancer, we performed a systematic review of published literature using gene\u2010environment or pharmacogenomic flags from two curated databases of genetic association studies, the Human Genome Epidemiology (HuGE) literature finder and Cancer Genome\u2010Wide 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u00d7E 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\u2010wide interaction studies (GEWIS). The most commonly reported measure was the interaction <jats:italic>P<\/jats:italic>\u2010value, of which a sizable number of <jats:italic>P<\/jats:italic>\u2010values were considered statistically significant (i.e., &lt;0.05). In addition, the magnitude of interactions reported was modest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Observations of published literature suggest that opportunity exists for increased sample size in G\u00d7E research, including GWAS\u2010identified loci in G\u00d7E studies, exploring more GWAS approaches in G\u00d7E such as GEWIS, and improving the reporting of G\u00d7E findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/gepi.21967","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T17:50:18Z","timestamp":1460310618000},"page":"356-365","source":"Crossref","is-referenced-by-count":86,"title":["Review of the Gene\u2010Environment Interaction Literature in Cancer: What Do We Know?"],"prefix":"10.1002","volume":"40","author":[{"given":"Naoko I.","family":"Simonds","sequence":"first","affiliation":[{"name":"Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armen A.","family":"Ghazarian","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla B.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences University of Massachusetts Medical School  Worcester Massachusetts United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheri D.","family":"Schully","sequence":"additional","affiliation":[{"name":"Office of Disease Prevention National Institutes of Health  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary L.","family":"Ellison","sequence":"additional","affiliation":[{"name":"Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Gillanders","sequence":"additional","affiliation":[{"name":"Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah E.","family":"Mechanic","sequence":"additional","affiliation":[{"name":"Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute  Bethesda Maryland United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-07-0598"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-012-1192-0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys010"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.3.381"},{"key":"e_1_2_6_6_1","unstructured":"Centers for Disease Control.2000.Gene\u2010Environment Interaction Fact Sheet. 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