The School of Public Health, Sun Yat-sen University, Guangzhou, China.
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2988. Epub 2017 Oct 10.
Immunoglobulin (Ig)A antibody of Epstein-Barr virus (EBV) was found to associate with breast cancer (BC), whereas IgA positivity was related to a series of genetic markers in the genes of homologous recombination repair system (HRRs). We assessed the associations of the polymorphisms in HRR genes with the risk and survival of BC.
A case-control study was conducted with 1551 bc cases and 1605 age-matched healthy controls between October 2008 and March 2012 in the Guangzhou Breast Cancer Study (GZBCS), China, and the case population were followed up until 31 January 2016. Five single nucleotide polymorphisms of candidate genes in HRR system were genotyped. Odds ratios (ORs) and hazards ratios (HRs) were calculated using multivariate logistic regression and Cox proportional hazards regression to estimate the risk and prognostic effect, respectively.
RFC1 rs6829064 (AA) was associated with an increased BC risk [OR = 1.35; 95% confidence interval (CI) = 1.06-1.73] compared to the wild genotype (GG). NRM rs1075496 (GT/TT versus GG) was associated with a worse progression-free survival (PFS) and the HR was 1.34 (95% CI = 1.01-1.78), particularly among advanced patients. LIG3 rs1052536 (CT/TT versus CC) was associated with a better PFS and the HR was 0.70 (95% CI = 0.53-0.93). However, RAD54L rs1710286 and RPA1 rs11078676 were not observed to be associated with either the risk or survival of BC.
The findings of the present study suggest that the polymorphisms in HRR genes were associated with BC risk (RFC1 rs6829064) and prognosis (NRM rs1075496 and LIG3 rs1052536), whereas RAD54L rs1710286 and RPA1 rs11078676 had null associations with BC.
研究发现，针对 Epstein-Barr 病毒（EBV）的免疫球蛋白（Ig）A 抗体与乳腺癌（BC）相关，而 IgA 阳性与同源重组修复系统（HRR）基因中一系列遗传标志物相关。我们评估了 HRR 基因多态性与 BC 风险和生存的相关性。
2008 年 10 月至 2012 年 3 月在中国广州乳腺癌研究（GZBCS）中进行了一项病例对照研究，共纳入 1551 例 BC 病例和 1605 例年龄匹配的健康对照，对病例人群进行随访直至 2016 年 1 月 31 日。对 HRR 系统候选基因中的 5 个单核苷酸多态性进行基因分型。采用多变量 logistic 回归和 Cox 比例风险回归分别计算比值比（OR）和风险比（HR），以估计风险和预后影响。
与野生基因型（GG）相比，RFC1 rs6829064（AA）与 BC 风险增加相关[OR=1.35；95%置信区间（CI）=1.06-1.73]。NRM rs1075496（GT/TT 与 GG）与无进展生存期（PFS）不良相关，风险比（HR）为 1.34（95%CI=1.01-1.78），特别是在晚期患者中。LIG3 rs1052536（CT/TT 与 CC）与更好的 PFS 相关，HR 为 0.70（95%CI=0.53-0.93）。然而，RAD54L rs1710286 和 RPA1 rs11078676 与 BC 的风险或生存均无关联。
本研究结果表明，HRR 基因多态性与 BC 风险（RFC1 rs6829064）和预后（NRM rs1075496 和 LIG3 rs1052536）相关，而 RAD54L rs1710286 和 RPA1 rs11078676 与 BC 无关联。
