Relationship between Rad51 G135C and G172T Variants and the Susceptibility to Cancer: A Meta-Analysis Involving 54 Case-Control Studies

<div><p>Background</p><p>The associations between Rad51 gene polymorphisms (G135C and G172T) and risk of cancer have been investigated, but the results were inconclusive. To get a comprehensive evaluation of the association above, we performed a meta-analysis of published studies.</p><p>Methods</p><p>A computerized search of PubMed, Embase and Web of Knowledge databases for all relevant studies was performed and the data were analyzed in a meta-analysis. The overall odds ratio (OR) with the 95% confidence interval (95% CI) was calculated to assess the strength of the association between Rad51 polymorphisms and cancer risk. Data were analyzed using fixed- or random-effects model when appropriate. Sensitivity analysis and publication bias test were also estimated.</p><p>Results</p><p>Overall, a total of 54 case-control studies were included in the current meta-analysis, among which 42 studies with 19,142 cases and 20,363 controls for RAD51 G135C polymorphism and 12 studies with 6,646 cases and 6,783 controls for G172T polymorphism. For G135C polymorphism, the pooled results indicated that significantly increased risk was found in overall cancers (homozygote model: OR = 1.776, 95% CI = 1.288–2.449; allelic genetic model: OR = 1.169, 95% CI = 1.016–1.345; recessive model: OR = 1.946, 95% CI = 1.336–2.835), especially in breast cancer (homozygote model: OR = 1.498, 95% CI = 1.026–2.189; recessive model: OR = 1.732, 95% CI  =  1.170–2.562). For G172T polymorphism, a decreased cancer risk was observed in head and neck cancer (homozygote model: OR  =  0.621, 95% CI  =  0.460–0.837; allelic genetic model: OR  =  0.824, 95% CI  =  0.716–0.948; recessive model: OR  =  0.639, 95% CI = 0.488–0.837).</p><p>Conclusions</p><p>Our results suggested that the Rad51 G135C polymorphism is a candidate for susceptibility to overall cancers, especially to breast cancer, and that the Rad51 G172T might play a protective role in the development of head and neck cancer.</p></div

Characteristics of the studies included on Rad51 G135C polymorphism.

<p>PB: population based; HB: hospital based; HWE: Hardy-Weinberg equilibrium (significant at the 0.05 level)</p><p>AML: acute myelocytic leukemia; HNC: head and neck cancer.</p

Flow chart explaining the selection of eligible studies included in the meta-analysis.

<p>Flow chart explaining the selection of eligible studies included in the meta-analysis.</p

Overall and subgroup results of the association between MTHFR C677T polymorphism and NSCL/P.

<p>Overall and subgroup results of the association between MTHFR C677T polymorphism and NSCL/P.</p

Meta-analysis of the Rad51 G135C polymorphism on cancer risk.

<p>P-values for ORs; <i>Ph</i> values of Q-test for heterogeneity test; I² refers to the proportion of total variation owing to between-study heterogeneity</p><p>Bold data represent the positive results.</p><p>PB: population based; HB: hospital based; AML: acute myelocytic leukemia; HNC: head and neck cancer</p>*<p>Random-effects model was used when <i>Ph</i> value for heterogeneity test <0.05; otherwise, fix-effects model was used.</p

Forest plot of association between MTHFR A1298C polymorphism and NSCL/P risk in mothers (T vs. C).

<p>Forest plot of association between MTHFR A1298C polymorphism and NSCL/P risk in mothers (T vs. C).</p

Association between MTHFR C677T and A1298C Polymorphisms and NSCL/P Risk in Asians: A Meta-Analysis

<div><p>Objective</p><p>Several studies have reported the association between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and nonsyndromic cleft lip with or without palate (NSCL/P) in Asian populations. However, findings have been conflicting. In order to investigate the association, a meta-analysis was performed.</p><p>Methods</p><p>We searched Pubmed, MedLine and EmBase database to selected eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated using fixed effects model or random effects model to assess the association between MTHFR polymorphisms and NSCL/P in both Asian children and mothers.</p><p>Results</p><p>Finally, nine case-control studies were included. Overall, the MTHFR C677T polymorphism and NSCL/P showed pooled ORs (95%CI) of 1.41(1.23–1.61) in Asian children, and 1.70(1.19–2.42) in Asian mothers. Subgroup analyses by geographical locations further identified the association in Eastern Asian children, Western/Central Asian children and mothers, but not in Eastern Asian mothers. However, no significant relationship between MTHFR A1298C polymorphism and NSCL/P was found in this meta-analysis.</p><p>Conclusions</p><p>The MTHFR 677T allele was associated with an increased risk of NSCL/P in Asian populations.</p></div

Forest plot of association between MTHFR C677T polymorphism and NSCL/P risk in children (T vs. C).

<p>Forest plot of association between MTHFR C677T polymorphism and NSCL/P risk in children (T vs. C).</p

The characteristics of eligible studies included in the meta-analysis.

<p><b>HWE</b> Hardy-Weinberg equilibrium; <b>HB</b> hospital based; <b>PB</b> population based.</p>a<p>two groups of control.</p