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single-nucleotide polymorphism (SNP) in the 5′-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers. A few studies have also investigated the genetic contribution of RAD51 135G>C to the risk of sporadic breast cancers or breast cancer in non-BRCA1/2 carriers, though the results are yet controversial and inconclusive. We, in this study, performed a more precise estimation of the relationship between 135G>C and breast cancer among non-BRCA1/2 mutation carriers by meta-analyzing the currently available evidence from the literature. A total of 12 studies involving 7,065 cases and 6,981 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. When all the studies were pooled into the meta-analysis, there was no evidence for a significant association between 135G>C and breast cancer risk in non-BRCA1/2 mutation carriers (for CC vs. GG: OR = 0.995, 95%CI: 0.741-1.336; for GC vs. GG: OR = 0.959, 95%CI: 0.869-1.057; for dominant model: OR = 0.988, 95%CI: 0.902-1.082; and for recessive model: OR = 1.037, 95%CI: 0.782-1.376). We also performed subgroup analysis by ethnicity (Caucasian) as well as did analysis using the studies fulfilling Hardy-Weinberg equilibrium, and the results did not change. In summary, the present meta-analysis suggests that the RAD51 135G>C does not modify breast cancer risk in non-BRCA1/2 mutation carriers. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5′ untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case-control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer. [ABSTRACT FROM AUTHOR]

Mutations in RAD51 gene are believed to be associated with elevated breast cancer risk. However, several case-control studies focusing on the association between RAD51 135G>C and breast cancer risk failed to achieve consensus. To clarify the effect of RAD51 135G>C polymorphism on breast cancer, a meta-analysis was performed. By searching PubMed and EMBASE, a total of 14 case-control studies, containing 12,183 cases and 10,183 controls, were included. The strength of association between RAD51 135G>C polymorphism and breast cancer risk was assessed by odds ratio (OR) with the corresponding 95% confidence interval (95% CI). When all the eligible studies were pooled into the meta-analysis, an elevated cancer risk was revealed in additive model (OR, 1.34; 95% CI, 1.01-1.78; P = 0.044) and recessive model (OR, 1.37; 95% CI, 1.03-1.82; P = 0.032). In subgroup analyses by ethnicity, BRCA1/2 mutation status, and family history, a significant association was found only among BRCA2 mutation carriers (additive model: OR, 4.92; 95% CI, 1.11-21.83; P = 0.036; recessive model: OR, 4.88; 95% CI, 1.10-21.67; P = 0.037). Sensitivity analysis did not perturb the results. In conclusion, this meta-analysis suggests that RAD51 variant 135C homozygote is associated with elevated breast cancer risk among BRCA2 mutation carriers. [ABSTRACT FROM AUTHOR]

Several studies have investigated the associations between RAD51 G135C polymorphism and the susceptibility to breast cancer, but results have been inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 case control studies, including 12,153 cases and 10,245 controls, were selected. Overall, significant decreased risk was found for the additive model (OR = 0.995, 95% CI = 0.991-0.998) and dominant model (OR = 0.994, 95% CI = 0.991-0.998). In the subgroup analysis by ethnicity, statistically significantly decreased risk was found in Asians (additive model: OR = 0.977, 95% CI = 0.954-1.000 and dominant model: OR = 0.981, 95% CI = 0.963-1.000). In conclusion, this meta-analysis suggests that the RAD51 G135C polymorphism is a low-penetrant risk factor for developing breast cancer. [ABSTRACT FROM AUTHOR]

RAD51 plays a key role in homologous recombination repair of double-stranded DNA breaks which may cause chromosomal breaks and genomic instability. We performed a meta-analysis of 9 epidemiological studies involving 13,241 cases and 13,203 controls that examined the association between RAD51 135G>C polymorphism and breast cancer. No significant association of RAD51 135G>C polymorphism with breast cancer was found in overall and European populations. However, after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded, we observed an overall significant increased breast cancer risk (for the recessive model CC vs. GG/CG: OR = 1.35, 95% CI = 1.05-1.74, P = 0.06). In summary, our meta-analysis suggested the RAD51 135G>C polymorphism may contribute to breast cancer susceptibility. [ABSTRACT FROM AUTHOR]