Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Breast Cancer Res Treat. 2011 Jan;125(2):479-87. doi: 10.1007/s10549-010-0959-z. Epub 2010 Jun 13.
X-ray repair cross-complementing 1 (XRCC1) plays a critical role in base excision repair and genetic variations of XRCC1 may be associated with cancer susceptibility. We tested this hypothesis by examining the contribution of polymorphism in the regulatory region of XRCC1 -77T>C to risk of breast cancer in 995 patients and 1,004 controls. We found this polymorphism was associated with an increased risk of breast cancer, with an OR of 1.25 (95% CI, 1.00-1.56) for the -77TC genotype and 2.55 (95% CI, 1.11-5.86) for the -77CC genotype compared with the -77TT genotype. Haplotype analysis combining the -77T>C with three well-studied non-synonymous polymorphisms (Arg194Trp, Arg280His, and Arg399Gln) showed that only the -77C-containing haplotype was associated with the risk. Moreover, the C allele had more than 3-fold decreased luciferase expression compared with the T allele in breast cancer cell line MCF-7 (P < 0.001). A meta-analysis of seven publications with a total 2,888 cancer cases and 3,177 controls demonstrated that -77C was significantly associated with cancer risk, with an OR of 1.34 (95% CI, 1.18-1.51) for the TC genotype and 1.53 (95% CI, 1.14-2.07) for the CC genotype compared with the TT genotype. In conclusion, these findings indicated that XRCC1 -77T>C polymorphism may be a genetic determinant for developing breast cancer.
X 射线修复交叉互补基因 1（XRCC1）在碱基切除修复中起着关键作用，而 XRCC1 的遗传变异可能与癌症易感性相关。我们通过检测 XRCC1 调控区多态性-77T>C 对 995 例患者和 1004 例对照的乳腺癌发病风险的影响，来验证这一假说。我们发现该多态性与乳腺癌发病风险增加相关，与 -77TT 基因型相比，-77TC 基因型的 OR 值为 1.25（95%CI：1.00-1.56），-77CC 基因型的 OR 值为 2.55（95%CI：1.11-5.86）。结合三个研究充分的非同义多态性（Arg194Trp、Arg280His 和 Arg399Gln）进行的单体型分析显示，只有包含-77C 的单体型与风险相关。此外，在乳腺癌细胞系 MCF-7 中，与 T 等位基因相比，C 等位基因的荧光素酶表达降低了 3 倍以上（P<0.001）。对包含 2888 例癌症病例和 3177 例对照的 7 项出版物的荟萃分析显示，与 TT 基因型相比，TC 基因型的 OR 值为 1.34（95%CI：1.18-1.51），CC 基因型的 OR 值为 1.53（95%CI：1.14-2.07）。综上所述，这些发现表明 XRCC1-77T>C 多态性可能是乳腺癌发生的遗传决定因素。
