PARP-1 rs1136410 Polymorphism and Gastrointestinal Cancer Risk: A Meta-Analysis of Cancer-Type and Ethnic-Specific...

Poly (ADP-ribose) polymerase-1 (PARP-1) is a key enzyme in DNA repair pathways and has been implicated in cancer susceptibility. The rs1136410 polymorphism in the PARP-1 gene has shown inconsistent associations with gastrointestinal cancer risk across populations. This meta-analysis aimed to evaluate the association between PARP-1 rs1136410 polymorphism and the risk of colorectal cancer (CRC) and gastric cancer (GC), with a focus on ethnic differences.

A systematic literature search was performed in PubMed, Scopus, EMBASE, Web of Science, Cochrane Library, BIOSIS, LILACS, CNKI, CBM, Wan Fang, and other regional databases up to February 1, 2025. Eligible case-control studies assessing the association between PARP- 1 rs1136410 polymorphism and CRC or GC were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under five genetic models using Comprehensive Meta-Analysis software.

Thirteen case-control studies were included, comprising 3.591 patients and 5.433 controls. For GC (8 studies; 1,784 cases and 2,521 controls), significant associations were observed under multiple genetic models: allele comparison (C vs. T: OR=2.01, 95% CI 1.04-3.91, p=0.039), homozygous comparison (CC vs. TT: OR=1.77, 95% CI 1.24-2.52, p=0.002), heterozygous comparison (CT vs. TT: OR=1.36, 95% CI 1.18-1.57, p<0.001), and recessive comparison (CC vs. CT+TT: OR=1.54, 95% CI 1.08-2.20, p=0.017). No significant association was detected for CRC (5 studies; 1.807 cases and 2.912 controls). Ethnic subgroup analysis revealed a protective effect against CRC in Caucasians but increased susceptibility in Asians.

The PARP-1 rs1136410 polymorphism is associated with elevated GC risk but not CRC, with ethnicity-dependent effects suggesting differential genetic susceptibility. These findings highlight the importance of considering population-specific genetic backgrounds in gastrointestinal cancer risk assessment, prevention, and precision medicine strategies.