PARP-1 Val762Ala polymorphism and risk of cancer: a meta-analysis based on 39 case-control studies.
BACKGROUND
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.


RESULTS
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).


CONCLUSIONS
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).
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Qin
Q
Qin
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Jing
J
Lu
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Hongcheng
H
Zhu
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Liping
L
Xu
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Hongyan
H
Cheng
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Liangliang
L
Zhan
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Xi
X
Yang
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Chi
C
Zhang
Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Xinchen
X
Sun
D000409:Alanine / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D011110:Polymorphism, Genetic; D014633:Valine / Q000235:genetics*
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D014633:Valine; D000409:Alanine