Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, 200032 Shanghai, People's Republic of China.
Breast Cancer Res Treat. 2010 Aug;123(1):219-25. doi: 10.1007/s10549-010-0753-y. Epub 2010 Feb 2.
Several common single-nucleotide polymorphisms (SNPs) within the XRCC2 gene have been identified as potential breast cancer susceptibility loci and a coding SNP in exon 3 (Arg188His, rs3218536) has been extensively studied, though the results were inconclusive. We, in this study, performed a more convincing and precise estimation of the relationship between Arg188His and breast cancer by meta-analyzing the currently available evidence from literature. A total of 16 studies involving 18,341 cases and 19,028 controls (37,369 subjects) were identified for meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. When all the studies were pooled into meta-analysis, there was no evidence of a significant association between Arg188His and breast cancer risk in any genetic models. Notably, Arg188His tended to be related to breast cancer in a fixed-effects, dominant model (OR = 0.922, 95% CI: 0.870-0.978, P = 0.007); however, since there was a between-study heterogeneity (P (h) = 0.014), we assessed the association using a random-effects model instead and no significance was observed (OR = 0.932, 95% CI: 0.852-1.020, P = 0.128). Subgroup analysis by ethnicity did not change the results. In summary, the present meta-analysis suggests that the XRCC2 Arg188His is not directly associated with breast cancer risk. However, considering that susceptibility is likely to be the result of a complex interplay between genetic variation and environmental factors, we cannot rule out the possibility of interactions between Arg188His and other variants. Further investigation on the influence of this SNP in modifying the relationship between environment exposures and breast cancer risk is still needed.
几种常见的 XRCC2 基因内单核苷酸多态性（SNPs）已被确定为潜在的乳腺癌易感基因座，并且exon 3 中的一个编码 SNP（Arg188His，rs3218536）已经得到了广泛研究，尽管结果尚无定论。我们在这项研究中，通过对文献中现有证据进行荟萃分析，更有说服力和更精确地评估了 Arg188His 与乳腺癌之间的关系。共纳入了 16 项研究，包括 18341 例病例和 19028 例对照（37369 例）进行荟萃分析。在共显性模型、显性模型和隐性模型中，使用粗比值比（OR）和 95%置信区间（CI）来评估关联的强度。当所有研究都纳入荟萃分析时，没有证据表明 Arg188His 与乳腺癌风险之间存在显著关联。值得注意的是，Arg188His 在固定效应、显性模型中与乳腺癌有一定的相关性（OR = 0.922，95%CI：0.870-0.978，P = 0.007）；然而，由于存在研究间异质性（P(h) = 0.014），我们使用随机效应模型评估了关联，没有观察到显著意义（OR = 0.932，95%CI：0.852-1.020，P = 0.128）。按种族进行亚组分析并没有改变结果。综上所述，本荟萃分析表明，XRCC2 Arg188His 与乳腺癌风险没有直接关联。然而，考虑到易感性可能是遗传变异和环境因素之间复杂相互作用的结果，我们不能排除 Arg188His 与其他变异之间存在相互作用的可能性。进一步研究这个 SNP 在修饰环境暴露与乳腺癌风险之间的关系的影响仍然是必要的。
