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A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.

ABSTRACT: INTRODUCTION: The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA. METHODS: Among the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer. RESULTS: We observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk. CONCLUSION: Our results support the hypothesis that genetic variation in XRCC1, particularly in Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic variation in XRCC1 Arg399Gln was associated with breast cancer risk only among women with a history of smoking cigarettes.

SUBMITTER: Patel AV

PROVIDER: S-EPMC1410742 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature

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A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.

Patel Alpa V AV Calle Eugenia E EE Pavluck Alexandre L AL Feigelson Heather Spencer HS Thun Michael J MJ Rodriguez Carmen C

Breast cancer research : BCR 20051121 6

<h4>Introduction</h4>The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society ...[more]

PMID: 16457697

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Project description:AimTo perform a systematic meta-analysis to investigate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk.MethodsRelevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity.ResultsEleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg's and Egger's tests did not find any obvious publication bias.ConclusionThe XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.

Project description:BackgroundPrevious studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk.MethodsThe PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals.ResultsNo significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models.ConclusionThe meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.

Dataset Information

A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.

Publications

A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.

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