Association between the XRCC3 T241M polymorphism and risk of cancer: Evidence from 157 case–control studies

• Published in: Gene Vol. 523; no. 1; pp. 10 - 19
• Main Authors: He, Xiao-Feng, Wei, Wu, Li, Jia-Lin, Shen, Xu-Liang, Ding, Da-peng, Wang, Su-Lan, Liu, Zhi-Zhong, Qin, Jiang-Bo, Wu, Li-Xia, Xie, Dao-Lin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2013
• Subjects: breast neoplasms; Breast Neoplasms - ethnology; Breast Neoplasms - genetics; Cancer; Case-Control Studies; colorectal neoplasms; confidence interval; Confidence Intervals; Databases, Genetic; DNA-Binding Proteins - genetics; Early Detection of Cancer - methods; European Continental Ancestry Group - genetics; Female; Genetic Association Studies - methods; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Geography; Humans; lung neoplasms; Lung Neoplasms - ethnology; Lung Neoplasms - genetics; melanoma; Meta-analysis; Odds Ratio; Polymorphism; Polymorphism, Genetic; risk; Risk Factors; stomach neoplasms; Susceptibility; urinary bladder neoplasms; Urinary Bladder Neoplasms - ethnology; Urinary Bladder Neoplasms - genetics; Whites; X-radiation; X-ray cross-complementing group 3; XRCC3; X-ray cross-complementing group 3; OR; Susceptibility; XRCC3; HRR; HR; CIs; BER; Meta-analysis; MMR; HWE; NER; NHEJ; DSBR; Polymorphism; Cancer
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.03.071

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR]=1.07, 95% confidence interval [CI]=1.00–1.13; recessive model: OR=1.15, 95% CI=1.08–1.23; additive model: OR=1.17, 95% CI=1.08–1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development. •XRCC3 T241M is associated with breast cancer risk, especially in Caucasians.•XRCC3 T241M is associated with bladder cancer risk, especially in Caucasians.•XRCC3 T241M is associated with lung cancer risk.•New studies are important for XRCC3 T241M association in some cancer types.•Our manuscript included 61,861 cases and 84,584 controls from 157 studies.