Abstract
Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; however, most previous case-control studies were small sized and biased. Additionally, recent studies suggested that XRCC1 polymorphisms could be a biomarker of response to platinum-based chemotherapy. A comprehensive search was conducted to retrieve eligible studies and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to measure association strength. A total of 13 studies were identified and analyzed. We found that the Arg194Trp polymorphism (Trp vs. Arg, OR=1.342, 95% CI: 1.176) was associated with increased risk of cervical cancer, while no significant association was found with Arg280His (His vs. Arg, OR=1.059, 95% CI: 0.863, 1.299) or Arg399Gln (Gln vs. Arg, OR=1.144, 95% CI: 0.938, 1.394). As for response to platinum- based chemotherapy, the variant XRCC1 399Gln allele (Gln vs. Arg, OR=0.345, 95% CI: 0.163, 0.729) was linked with a poor response; however, the Arg194Trp polymorphism (TrpArg vs. ArgArg, OR=6.421, 95% CI: 1.573, 26.205) predicted a good response. The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response.
Highlights
Uterine cervical cancer is one of the worldwide most common malignant cancers and a leading cause of death in women
The disequilibrium of HardyWinberg equilibrium (HWE) was detected for Arg280His polymorphism in 1 study (Xiao-qin; et al, 2010) and Arg194Trp polymorphism in 2 studies (Barbisan et al, 2011; Settheetham-Ishida et al, 2011), and the 2 studies were not excluded because no disequilibrium was found in the Arg399Gln polymorphism
x-ray repair cross-complementing protein 1 (XRCC1) belongs to the DNA base excision repair (BER) pathway and repairs single-strand breaks and XRCC1 is crucial to the integrity of chromosome
Summary
Uterine cervical cancer is one of the worldwide most common malignant cancers and a leading cause of death in women. Studies have demonstrated that functional single nucleotide polymorphisms (SNPs) of XRCC1 are associated with cancer risks, such as lung cancer (Dai et al, 2012), bladder cancer (Narter et al, 2009), gastric cancer (Xue et al, 2011) and other cancers (Przybylowska-Sygut et al, 2012). Functional single nucleotide polymorphisms of x-ray repair cross-complementing protein 1 (XRCC1) have been suspected to contribute to uterine cervical cancer risk for a long time; most previous case-control studies were small sized and biased. Conclusion: The Arg194Trp polymorphism of XRCC1 increases risk of cervical cancer; the variant 399Gln allele predicts poor response to platinum-based chemotherapy, while the Arg194Trp polymorphism indicates a good response
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