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A role for XRCC2 gene polymorphisms in breast cancer risk and survival.

ABSTRACT: BACKGROUND:The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer. METHODS:The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC). RESULTS:The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10(-4), minor allele frequency (MAF)=0.23). This SNP yielded an OR(rec) of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-OR(rec) of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01). CONCLUSIONS:These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.

SUBMITTER: Lin WY

PROVIDER: S-EPMC3932658 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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A role for XRCC2 gene polymorphisms in breast cancer risk and survival.

Lin Wei-Yu WY Camp Nicola J NJ Cannon-Albright Lisa A LA Allen-Brady Kristina K Balasubramanian Sabapathy S Reed Malcolm W R MW Hopper John L JL Apicella Carmel C Giles Graham G GG Southey Melissa C MC Milne Roger L RL Arias-Pérez Jose I JI Menéndez-Rodríguez Primitiva P Benítez Javier J Grundmann Magdalena M Dubrowinskaja Natalia N Park-Simon Tjoung-Won TW Dörk Thilo T Garcia-Closas Montserrat M Figueroa Jonine J Sherman Mark M Lissowska Jolanta J Easton Douglas F DF Dunning Alison M AM Rajaraman Preetha P Sigurdson Alice J AJ Doody Michele M MM Linet Martha S MS Pharoah Paul D PD Schmidt Marjanka K MK Cox Angela A

Journal of medical genetics 20110531 7

<h4>Background</h4>The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.<h4>Methods</h4>The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and surv ...[more]

PMID: 21632523

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Project description:BackgroundGenetic variability in DNA double-strand break repair genes such as RAD51 gene and its paralogs XRCC2、XRCC3 may contribute to the occurrence and progression of breast cancer. To obtain a complete evaluation of the above association, we performed a meta-analysis of published studies.MethodsElectronic databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, were comprehensively searched from inception to September 2022. The Newcastle-Ottawa Scale (NOS) checklist was used to assess all included non-randomized studies. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by STATA 16.0 to assess the strength of the association between single nucleotide polymorphisms (SNPs) in these genes and breast cancer risk. Subsequently, the heterogeneity between studies, sensitivity, and publication bias were performed. We downloaded data from The Cancer Genome Atlas (TCGA) and used univariate and multivariate Cox proportional hazard regression (CPH) models to validate the prognostic value of these related genes in the R software.ResultsThe combined results showed that there was a significant correlation between the G172T polymorphism and the susceptibility to breast cancer in the homozygote model (OR= 1.841, 95% CI=1.06-3.21, P=0.03). Furthermore, ethnic analysis showed that SNP was associated with the risk of breast cancer in Arab populations in homozygous models (OR=3.52, 95% CI=1.13-11.0, P= 0.003). For the XRCC2 R188H polymorphism, no significant association was observed. Regarding polymorphism in XRCC3 T241M, a significantly increased cancer risk was only observed in the allelic genetic model (OR=1.05, 95% CI= 1.00-1.11, P=0.04).ConclusionsIn conclusion, this meta-analysis suggests that Rad51 G172T polymorphism is likely associated with an increased risk of breast cancer, significantly in the Arab population. The relationship between the XRCC2 R188H polymorphism and breast cancer was not obvious. And T241M in XRCC3 may be associated with breast cancer risk, especially in the Asian population.

Dataset Information

A role for XRCC2 gene polymorphisms in breast cancer risk and survival.

Publications

A role for XRCC2 gene polymorphisms in breast cancer risk and survival.

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