A Case-Control Study on Combined Effects of Base Excision Repair and Nucleotide Excision Repair Gene Polymorphisms in...

Gastrointestinal (GI) cancer constitute a major global health problem influenced by genetic and environmental factors. Genetic variations within base excision repair (BER and) nucleotide exchange repair (NER) pathway genes can impact DNA repair capacity. Investigating the combined effects of BER and NER pathway genes offers a promising avenue for understanding their impact on cancer susceptibility. This study was aimed to address combined effects of genetic variants in BER and NER on the risk of developing GI cancer.

Genetic polymorphisms within BER and NER genes were examined in two hundred histologically confirmed GI cancer cases, along with equal number of controls by the PCR-RFLP technique. Odds ratios (OR) with 95% CI and associated p-values were computed to assess an extent of association of these polymorphisms with GI cancer susceptibility, with statistical significance established at p ≤0.005.

Regression analysis revealed compelling evidence of synergistic effects between specific variant genotypes. Notably, combinations involving variants of XPG (rs17655) and XRCC1 (rs1799782) (OR=2.20; 95% CI: 1.02-4.72; p=0.042) and  XRCC1 (rs25487) (OR=2.56; 95% CI: 1.39-4.72; p=0.002) as well as XPD (rs238406) and XRCC1 (rs1799782) (OR=3.02; 95% CI: 1.60-5.70; p=0.0006) and XCC1 (rs25487)  (OR=6.63; 95% CI: 3.63-12.10; p=0.0001) exhibited significant associations with increased GI cancer risk within the study population.

These findings suggested combined influence of SNPs within XRCC1, XRCC3, and APE1, in combination with polymorphisms of XPC and XPD, on the development of GI cancer. Nonetheless, further investigations on larger scale are warranted to validate and expand upon these observations.