Association between the PARP1 Val762Ala polymorphism and cancer risk: evidence from 43 studies

Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial.

We searched literatures from MEDLINE, EMBASE and CBM pertaining to such associations, and then calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using random-effects model. The false-positive report probability (FPRP) analysis was used to confirm the validity of significant findings. Moreover, potential effects of rs1136410 variants on PARP1 mRNA expression were analyzed for three ethnicities by combining data from HapMap (genotype) and SNPexp (mRNA expression).

The final meta-analysis incorporated 43 studies, consisting of 17,351 cases and 22,401 controls. Overall, our results did not suggest significant associations between Ala variant (Ala/Ala or Ala/Val genotype) and cancer risk. However, further stratification analysis showed significantly increased risk for gastric cancer (Ala/Ala vs. Val/Val: OR = 1.56, 95% CI = 1.01-2.42, Ala/Val vs. Val/Val: OR = 1.34, 95% CI = 1.14-1.58, dominant model: OR = 1.41, 95% CI = 1.21-1.65 and Ala vs. Val: OR = 1.29, 95% CI = 1.07-1.55). On the contrary, decreased risk for brain tumor (Ala/Val vs. Val/Val: OR = 0.77, 95% CI = 0.68-0.87, dominant model: OR = 0.77, 95% CI = 0.68-0.87 and Ala vs. Val: OR = 0.82, 95% CI = 0.74-0.91). Additionally, we found that the Ala carriers had a significantly increased risk in all models for Asians. Our mRNA expression data provided further biological evidence to consolidate this finding.

Despite some limitations, this meta-analysis found evidence for an association between the PAPR1 Val762Ala and cancer susceptibility within gastric cancer, brain tumor and Asian subgroups.