Qin Qin, Lu Jing, Zhu Hongcheng, Xu Liping, Cheng Hongyan, Zhan Liangliang, Yang Xi, Zhang Chi, Sun Xinchen
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
PLoS One. 2014 May 22;9(5):e98022. doi: 10.1371/journal.pone.0098022. eCollection 2014.
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).
聚（ADP - 核糖）聚合酶 - 1（PARP - 1）是一种与核染色质相关的酶，参与多种重要的细胞过程，尤其是在DNA修复系统中。PARP - 1 rs1136410：C>T是研究最多的多态性之一，可能与人类致癌作用有关。然而，先前研究的结果尚无定论。因此，进行了一项荟萃分析，以更精确地估计该酶的作用。
在PubMed和EMBASE数据库中进行了全面检索，直至2013年12月9日。根据纳入和排除标准，共有39项研究（16,783例癌症病例和23,063例对照受试者）纳入荟萃分析。当所有研究汇总分析时，未发现PARP - 1 Val762Ala多态性与癌症风险之间存在显著关联（VA + AA与VV相比：OR = 1.03，95% CI = 0.95 - 1.11）。癌症类型的亚组分析显示，-762Ala等位基因与胃癌、宫颈癌和肺癌风险增加以及神经胶质瘤风险降低有关。此外，在亚洲后裔中观察到与该多态性相关的癌症风险显著增加（VA + AA与VV相比：OR = 1.17，95% CI = 1.09 - 1.25；AA与VV相比：OR = 1.28，95% CI = 1.08 - 1.51；VA与VV相比：OR = 1.12，95% CI = 1.04 - 1.20；AA与VA + VV相比：OR = 1.09，95% CI = 1.03 - 1.39）。这些结果还表明，PARP - 1 Val762Ala和XRCC1 Arg399Gln之间的联合作用可能与癌症发生风险有关（OR = 3.53，95% CI = 1.30 - 9.59）。
本荟萃分析提供了证据，表明PARP - 1 Val762Ala可能至少在某些种族群体（亚洲人）或某些特定癌症类型（胃癌、宫颈癌、肺癌和神经胶质瘤）中参与癌症发生。
