title: A functional -77T>C polymorphism in XRCC1 is associated with risk of breast cancer.
abstract: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Yihua
authors.initials: Y
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Shengyu
authors.initials: S
authors.lastname: Duan
authors.forename: Rui
authors.initials: R
authors.lastname: Rui
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
authors.forename: Shaofa
authors.initials: S
authors.lastname: Nie
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human