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XRCC2 Arg188His polymorphism is not directly associated with breast cancer risk: evidence from 37,369 subjects

  • Epidemiology
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Abstract

Several common single-nucleotide polymorphisms (SNPs) within the XRCC2 gene have been identified as potential breast cancer susceptibility loci and a coding SNP in exon 3 (Arg188His, rs3218536) has been extensively studied, though the results were inconclusive. We, in this study, performed a more convincing and precise estimation of the relationship between Arg188His and breast cancer by meta-analyzing the currently available evidence from literature. A total of 16 studies involving 18,341 cases and 19,028 controls (37,369 subjects) were identified for meta-analysis. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. When all the studies were pooled into meta-analysis, there was no evidence of a significant association between Arg188His and breast cancer risk in any genetic models. Notably, Arg188His tended to be related to breast cancer in a fixed-effects, dominant model (OR = 0.922, 95% CI: 0.870–0.978, P = 0.007); however, since there was a between-study heterogeneity (P h = 0.014), we assessed the association using a random-effects model instead and no significance was observed (OR = 0.932, 95% CI: 0.852–1.020, P = 0.128). Subgroup analysis by ethnicity did not change the results. In summary, the present meta-analysis suggests that the XRCC2 Arg188His is not directly associated with breast cancer risk. However, considering that susceptibility is likely to be the result of a complex interplay between genetic variation and environmental factors, we cannot rule out the possibility of interactions between Arg188His and other variants. Further investigation on the influence of this SNP in modifying the relationship between environment exposures and breast cancer risk is still needed.

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Acknowledgments

This research is supported by grants from the National Basic Research Program of China (2006CB910501), 2009 Youth Foundation of Shanghai Public Health Bureau, and the National Natural Science Foundation of China (30971143, 30972936).

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Authors and Affiliations

  1. Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, 200032, Shanghai, People’s Republic of China

    Ke-Da Yu, Ao-Xiang Chen, Li-Xin Qiu, Lei Fan, Chen Yang & Zhi-Ming Shao

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

    Ke-Da Yu, Ao-Xiang Chen, Lei Fan, Chen Yang & Zhi-Ming Shao

  3. Department of Medical Oncology, Cancer Hospital, Fudan University, Shanghai, People’s Republic of China

    Li-Xin Qiu

  4. Institutes of Biomedical Science, Fudan University, Shanghai, People’s Republic of China

    Zhi-Ming Shao

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  1. Ke-Da Yu
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Correspondence to Zhi-Ming Shao.

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Ke-Da Yu and Ao-Xiang Chen have contributed equally to this work.

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Yu, KD., Chen, AX., Qiu, LX. et al. XRCC2 Arg188His polymorphism is not directly associated with breast cancer risk: evidence from 37,369 subjects. Breast Cancer Res Treat 123, 219–225 (2010). https://doi.org/10.1007/s10549-010-0753-y

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