<i>PARP-1 Val762Ala</i> Polymorphism and Risk of Cancer: A Meta-Analysis Based on 39 Case-Control Studies

<div><p>Background</p><p>Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear chromatin-associated enzyme involved in several important cellular processes, particularly in the DNA repair system. <i>PARP-1</i> rs1136410: C>T is among the most studied polymorphisms and likely involved in human carcinogenesis. However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this enzyme.</p><p>Methodology and Principal Findings</p><p>A comprehensive search was conducted in the PubMed and EMBASE databases until December 9, 2013. A total of 39 studies with 16,783 cancer cases and 23,063 control subjects were included in the meta-analysis on the basis of the inclusion and exclusion criteria. No significant association between the <i>PARP-1 Val762Ala</i> polymorphism and cancer risk was found when all of the studies were pooled into the analysis (VA + AA vs. VV: OR = 1.03, 95% CI = 0.95–1.11). The subgroup analysis of cancer types revealed that the –762Ala allele was associated with increased risk of gastric, cervical, and lung cancers and a decreased risk of glioma. In addition, a significantly increased risk of cancer associated with the polymorphism was observed in Asian descendents (VA + AA vs. VV: OR = 1.17, 95% CI = 1.09–1.25; AA vs. VV: OR = 1.28, 95% CI = 1.08–1.51; VA vs. VV: OR = 1.12, 95% CI = 1.04–1.20; AA vs. VA + VV: OR = 1.09, 95% CI = 1.03–1.39). These results also indicated that a joint effect between <i>PARP-1 Val762Ala</i> and <i>XRCC1 Arg399Gln</i> could be involved in the risk of cancer development (OR = 3.53, 95% CI = 1.30–9.59).</p><p>Conclusion</p><p>The present meta-analysis provides evidence that the <i>PARP-1 Val762Ala</i> may be involved in cancer development at least in some ethnic groups (Asian) or some specific cancer types (gastric, cervical, and lung cancers, and glioma).</p>