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

Abstract

BackgroundThe 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.MethodsA 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.ResultsOverall, 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).ConclusionsOur 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.

Homologous Recombination Repair Polymorphisms, Cancer Susceptibility and Treatment Outcome

“…Another RAD51 polymorphism, rs1801321 was investigated in only one meta-analysis and even though overall cancer risk was not modified [54], the decreased risk in carriers of polymorphic allele for head and neck cancer confirmed the results of previous studies [24]. Decreased breast cancer risk was also observed in carriers of polymorphic allele [58].…”

“…RAD51 rs1801320 SNP was also associated with increased overall cancer risk in the two largest meta-analyses that included more than 40 individual studies [54,55], however no association was observed in an earlier study [56]. Increased risk for several cancer types, including hematological malignancies, ovarian, colorectal, and endometrial cancer was observed in a recent study [55], but not all were replicated in other studies (Table 4).…”

“…More recent meta-analyses are presented in Table 4. Some suggested that rs1801320 may increase breast cancer susceptibility [54,55], but one of the studies suggested a potential role of this polymorphism only in individuals with BRCA2 mutations [56]. BRCA2 directly interacts with RAD51 and influences intracellular transport as well as function of RAD51 [57], thus playing an important role in HRR, so these observations are biologically plausible.…”

Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer

“…XRCC3 protein is another important protein, structurally and functionally related to RAD51, which plays an important role in the homologous recombination repair system (Krupa et al, 2011). A number of epidemiological studies have evaluated the association between RAD51 135G/C, 172 G/T and XRCC3 Thr241Met polymorphisms with pathogenesis of different cancer (Wang et al, 2013;Mao et al, 2014;Zhao et al, 2014). However, limited numbers of studies are available for above mentioned polymorphisms and HNC patients with inconclusive results.…”

Rad51 paralogs and the risk of unselected breast cancer: A case-control study

“…Both these SNPs were reported to be associated with altered gene transcription [22,23]. Large meta-analyses have shown that 135 C allele increases the general risk as well as the risk of BrC, with a distinct dosedependent effect [10,24]. The 172 T allele-containing genotypes, on the other-hand, were found to be associated with some 25% reduction of general odds of cancer compared to the 172 GG wild-type one [10].…”