Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei, China; Department of Surgery, Hebei General Hospital, Shijiazhuang, Hebei, China; Department of Oncology & Immunotherapy, Hebei General Hospital, Shijiazhuang, Hebei, China; Department of Surgery, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China.
Department of Surgery, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China.
PLoS One. 2014 Mar 18;9(3):e92083. doi: 10.1371/journal.pone.0092083. eCollection 2014.
Converging evidence supports the central role of DNA damage in progression to breast cancer. We therefore in this study aimed to assess the potential interactions of seven common polymorphisms from five DNA repair genes (XRCC1, XRCC2, XRCC3, XPA and APEX1) in association with breast cancer among Han Chinese women.
METHODOLOGY/PRINCIPAL FINDINGS: This was a case-control study involving 606 patients diagnosed with sporadic breast cancer and 633 age- and ethnicity-matched cancer-free controls. The polymerase chain reaction-ligase detection reaction method was used to determine genotypes. All seven polymorphisms were in accordance with Hardy-Weinberg equilibrium in controls. Differences in the genotypes and alleles of XRCC1 gene rs25487 and XPA gene rs1800975 were statistically significant between patients and controls, even after the Bonferroni correction (P<0.05/7). Accordingly, the risk for breast cancer was remarkably increased for rs25487 (OR = 1.28; 95% CI: 1.07-1.51; P = 0.006), but decreased for rs1800975 (OR = 0.77; 95% CI: 0.67-0.90; P = 0.001) under an additive model at a Bonferroni corrected alpha of 0.05/7. Allele combination analysis showed higher frequencies of the most common combination C-G-G-C-G-G-G (alleles in order of rs1799782, rs25487, rs3218536, rs861539, rs1800975, rs1760944 and rs1130409) in controls than in patients (PSim = 0.002). In further interaction analysis, two-locus model including rs1800975 and rs25487 was deemed as the overall best model with the maximal testing accuracy of 0.654 and the cross-validation consistency of 10 out of 10 (P = 0.001).
Our findings provide clear evidence that XRCC1 gene rs25487 and XPA gene rs1800975 might exert both independent and interactive effects on the development of breast cancer among northern Chinese women.
越来越多的证据表明 DNA 损伤在乳腺癌的进展中起着核心作用。因此，本研究旨在评估五个 DNA 修复基因（XRCC1、XRCC2、XRCC3、XPA 和 APEX1）中的七个常见多态性与汉族女性乳腺癌之间的潜在相互作用。
方法/主要发现：这是一项病例对照研究，涉及 606 名确诊为散发性乳腺癌的患者和 633 名年龄和种族匹配的无癌对照。聚合酶链反应-连接酶检测反应方法用于确定基因型。所有七种多态性在对照组中均符合哈迪-温伯格平衡。XRCC1 基因 rs25487 和 XPA 基因 rs1800975 的基因型和等位基因在患者和对照组之间存在统计学差异，即使经过 Bonferroni 校正（P<0.05/7）。因此，rs25487 的乳腺癌风险显著增加（OR=1.28；95%CI：1.07-1.51；P=0.006），而 rs1800975 的风险降低（OR=0.77；95%CI：0.67-0.90；P=0.001），在 Bonferroni 校正后的α为 0.05/7。等位基因组合分析显示，最常见的组合 C-G-G-C-G-G-G（按 rs1799782、rs25487、rs3218536、rs861539、rs1800975、rs1760944 和 rs1130409 的顺序）在对照组中的频率高于患者（PSim=0.002）。在进一步的相互作用分析中，包括 rs1800975 和 rs25487 的双位点模型被认为是总体最佳模型，其最大检测准确率为 0.654，10 次交叉验证一致性为 10 次（P=0.001）。
我们的研究结果提供了明确的证据，表明 XRCC1 基因 rs25487 和 XPA 基因 rs1800975 可能在中国北方女性乳腺癌的发生中发挥独立和交互作用。
