Rajaei Mehrdad, Saadat Iraj, Omidvari Shahpour, Saadat Mostafa
Department of Biology, College of Sciences, Shiraz University, 71454, Shiraz, Iran.
Med Oncol. 2014 Apr;31(4):885. doi: 10.1007/s12032-014-0885-8. Epub 2014 Mar 11.
Variation in DNA repair genes is one of the mechanisms that may lead to variation in DNA repair capacity. Ku, a heterodimeric DNA-binding complex, is directly involved in repair of DNA double-strand breaks. Ku consists of two subunits, Ku70 and Ku80, which are encoded by the XRCC6 and XRCC5 genes, respectively. In the present study, we investigated whether common genetic variant in variable number of tandem repeats (VNTR) XRCC5 and T-991C XRCC6 was associated with an altered risk of breast cancer. The present study included 407 females with breast cancer and 395 age frequency-matched controls which were randomly selected from the healthy female blood donors. The XRCC5 and XRCC6 polymorphisms were determined using PCR-based methods. For XRCC5 polymorphism, in comparison with the 1R/1R genotype, the 0R/0R genotype increased breast cancer risk (OR 9.55, 95%CI 1.19-76.64, P = 0.034). The 1R/3R genotype compared with 1R/1R genotype decreased the risk of breast cancer (Fisher's exact test P = 0.015). There was no association between T-991C polymorphism of XRCC6 and breast cancer risk. Mean of age at diagnosis of breast cancer for 0, 1, 2, 3, and >4 repeat in XRCC5 were 39.2, 41.9, 44.3, 45.8, and 47.3 years, respectively. The Kaplan-Meier survival analysis revealed that the number of repeat was associated with age at diagnosis of breast cancer (log rank statistic = 13.90, df = 4, P = 0.008). The findings of the present study revealed that either breast cancer risk or age at diagnosis of breast cancer was associated with the VNTR polymorphism at promoter region of XRCC5.
DNA修复基因的变异是可能导致DNA修复能力变异的机制之一。Ku是一种异源二聚体DNA结合复合物，直接参与DNA双链断裂的修复。Ku由两个亚基Ku70和Ku80组成，它们分别由XRCC6和XRCC5基因编码。在本研究中，我们调查了可变数目串联重复序列（VNTR）XRCC5和T-991C XRCC6中的常见基因变异是否与乳腺癌风险改变相关。本研究纳入了407例乳腺癌女性患者和395例年龄频率匹配的对照，这些对照是从健康女性献血者中随机选取的。使用基于PCR的方法确定XRCC5和XRCC6的多态性。对于XRCC5多态性，与1R/1R基因型相比，0R/0R基因型增加了乳腺癌风险（比值比9.55，95%置信区间1.19 - 76.64，P = 0.034）。与1R/1R基因型相比，1R/3R基因型降低了乳腺癌风险（Fisher精确检验P = 0.015）。XRCC6的T-991C多态性与乳腺癌风险之间无关联。XRCC5中0、1、2、3和>4个重复序列的乳腺癌诊断平均年龄分别为39.2岁、41.9岁、44.3岁、45.8岁和47.3岁。Kaplan-Meier生存分析显示，重复序列数量与乳腺癌诊断年龄相关（对数秩统计量 = 13.90，自由度 = 4，P = 0.008）。本研究结果表明，乳腺癌风险或乳腺癌诊断年龄均与XRCC5启动子区域的VNTR多态性相关。
