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Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?

ABSTRACT: 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.

SUBMITTER: Simonds NI

PROVIDER: S-EPMC4911236 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?

Simonds Naoko I NI Ghazarian Armen A AA Pimentel Camilla B CB Schully Sheri D SD Ellison Gary L GL Gillanders Elizabeth M EM Mechanic Leah E LE

Genetic epidemiology 20160407 5

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27061572

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Project description:BACKGROUND: The paper hand-held record (PHR) has been widely used as a tool to facilitate communication between health care providers and a pregnant woman. Since its inception in the 1950s, it has been described as a successful initiative, evolving to meet the needs of communities and their providers. Increasingly, the electronic health record (EHR) has dominated the healthcare arena and the maternity general practice shared-care arrangement seems to have adopted this initiative. A systematic review was conducted to determine perspectives of the PHR and the EHR with regards to data completeness; experiences of users and integration of care between women and health care providers. METHOD: A literature search was conducted that included papers from 1985 to 2012. Studies were chosen if they fulfilled the inclusion criteria, reporting on: data completeness; experiences of users and integration of care between women and health care providers. Papers were extracted by one reviewer in consultation with two reviewers with expertise in maternity e-health and independently assessed for quality. RESULTS: A total of 43 papers were identified for the review, from an initial 6,816 potentially relevant publications. No papers were found that reported on data completeness in a maternity PHR or a maternity EHR, in a shared-care setting. Women described the PHR as important to their antenatal care and had a generally positive perception of using an EHR. Hospital clinicians reported generally positive experiences using a PHR, while both positive and negative impressions were found using an EHR. The few papers describing the use of the PHR and EHR by community clinicians were also divergent and inconclusive with regards to their experiences. In a general practice shared-care model, the PHR is a valuable tool for integration between the woman and the health care provider. While the EHR is an ideal initiative in the maternity setting, facilitating referrals and communication, there are issues of fragmentation and continued paper use. CONCLUSIONS: There was a surprising gap in knowledge surrounding data completeness on maternity PHRs or EHRs. There is also a paucity of available impressions from community clinicians using both forms of the records.

Project description:The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene-environment interactions are poorly understood. Recently developed approaches that treat transcript abundances of thousands of genes as quantitative traits offer the opportunity to broadly characterize the architecture of gene-environment interactions. We examined the genetic and molecular basis of variation in gene expression between two yeast strains (BY and RM) grown in two different conditions (glucose and ethanol as carbon sources). We observed that most transcripts vary by strain and condition, with 2,996, 3,448, and 2,037 transcripts showing significant strain, condition, and strain-condition interaction effects, respectively. We expression profiled over 100 segregants derived from a cross between BY and RM in both growth conditions, and identified 1,555 linkages for 1,382 transcripts that show significant gene-environment interaction. At the locus level, local linkages, which usually correspond to polymorphisms in cis-regulatory elements, tend to be more stable across conditions, such that they are more likely to show the same effect or the same direction of effect across conditions. Distant linkages, which usually correspond to polymorphisms influencing trans-acting factors, are more condition-dependent, and often show effects in different directions in the two conditions. We characterized a locus that influences expression of many growth-related transcripts, and showed that the majority of the variation is explained by polymorphism in the gene IRA2. The RM allele of IRA2 appears to inhibit Ras/PKA signaling more strongly than the BY allele, and has undergone a change in selective pressure. Our results provide a broad overview of the genetic architecture of gene-environment interactions, as well as a detailed molecular example, and lead to key insights into how the effects of different classes of regulatory variants are modulated by the environment. These observations will guide the design of studies aimed at understanding the genetic basis of complex traits.

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Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?

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Review of the Gene-Environment Interaction Literature in Cancer: What Do We Know?

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