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Smoking and selected DNA repair gene polymorphisms in controls: systematic review and meta-analysis.

ABSTRACT: When the case-only study design is used to estimate statistical interaction between genetic (G) and environmental (E) exposures, G and E must be independent in the underlying population, or the case-only estimate of interaction (COR) will be biased. Few studies have examined the occurrence of G-E association in published control group data.To examine the assumption of G-E independence in empirical data, we conducted a systematic review and meta-analysis of G-E associations in controls for frequently investigated DNA repair genes (XRCC1 Arg399Gln, Arg194Trp, or Arg280His, XPD Lys751Gln, and Asp312Asn, and XRCC3 Thr241Met), and smoking (ever/never smoking, current/not current smoker, smoking duration, smoking intensity, and pack-years).Across the 55 included studies, single nucleotide polymorphisms SNP-smoking associations in controls (OR(z)) were not reliably at the null value of 1.0 for any SNP-smoking combinations. Two G-E combinations were too heterogeneous for summary estimates: XRCC1 399 and ever-never smoking (N = 21), and XPD 751 and pack-years (N = 12). OR(z) ranges for these combinations were: [OR(z) (95% confidence interval (CI)] 0.7 (0.4, 1.2)-1.9 (1.2, 2.8) and 0.8 (0.5, 1.3)-2.3 (0.8, 6.1), respectively). Estimates for studies considered homogeneous (Cochran's Q P-value <0.10) varied 2- to 5-fold. No study characteristics were identified that could explain heterogeneity.We recommend the independence assumption be evaluated in the population underlying any potential case-only study, rather than in a proxy control group(s) or pooled controls.These results suggest that G-E association in controls may be population-specific. Increased access to control data would improve evaluation of the independence assumption.

SUBMITTER: Hodgson ME

PROVIDER: S-EPMC3108462 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Smoking and selected DNA repair gene polymorphisms in controls: systematic review and meta-analysis.

Hodgson M Elizabeth ME Poole Charles C Olshan Andrew F AF North Kari E KE Zeng Donglin D Millikan Robert C RC

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20101008 12

<h4>Background</h4>When the case-only study design is used to estimate statistical interaction between genetic (G) and environmental (E) exposures, G and E must be independent in the underlying population, or the case-only estimate of interaction (COR) will be biased. Few studies have examined the occurrence of G-E association in published control group data.<h4>Methods</h4>To examine the assumption of G-E independence in empirical data, we conducted a systematic review and meta-analysis of G-E ...[more]

PMID: 20935063

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Project description:BACKGROUND AND OBJECTIVE: The X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study. METHODS: PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status. RESULTS: A total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively). CONCLUSIONS: This meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.

Dataset Information

Smoking and selected DNA repair gene polymorphisms in controls: systematic review and meta-analysis.

Publications

Smoking and selected DNA repair gene polymorphisms in controls: systematic review and meta-analysis.

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