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

• Published in: PloS one Vol. 9; no. 5; p. e98022
• Main Authors: Qin, Qin, Lu, Jing, Zhu, Hongcheng, Xu, Liping, Cheng, Hongyan, Zhan, Liangliang, Yang, Xi, Zhang, Chi, Sun, Xinchen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.05.2014; Public Library of Science (PLoS)
• Subjects: Adenosine diphosphate; Alanine - genetics; Apoptosis; Biomarkers; Bladder cancer; Breast cancer; Cancer; Cancer research; Carcinogenesis; Carcinogens; Case-Control Studies; Cell cycle; Cervix; Chromatin; Deoxyribonucleic acid; Development and progression; DNA; DNA damage; DNA repair; Enzymes; Genes; Genetic aspects; Genetic Predisposition to Disease; Glioma; Gliomas; Health aspects; Health risk assessment; Health risks; Humans; Ionizing radiation; Lung cancer; Lungs; Medicine and Health Sciences; Meta-analysis; Minority & ethnic groups; Monosaccharides; Neoplasms - genetics; Oncology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - genetics; Polymorphism; Polymorphism, Genetic; Proteins; Ribose; Risk; Risk factors; Risk reduction; Studies; Subgroups; Valine - genetics; XRCC1 protein; China
• DOI: 10.1371/journal.pone.0098022
• ISSN: 1932-6203

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. PARP-1 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. 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 PARP-1 Val762Ala 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 PARP-1 Val762Ala and XRCC1 Arg399Gln could be involved in the risk of cancer development (OR = 3.53, 95% CI = 1.30-9.59). The present meta-analysis provides evidence that the PARP-1 Val762Ala 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).