Association of XRCC1 Arg399Gln and RAD51 135 G>C Polymorphisms and Epidemiologic Risk Factors with Colorectal Cancer Among Selected Filipinos
Objectives. Several studies have demonstrated that genetic variants of certain DNA repair genes such as the RAD51 and XRCC1 increase cancer risk substantially. The results were also observed to be race- and tumor site specific. Hence, this study aimed to determine the possible association of XRCC1 Arg399Gln and RAD51 135G>C polymorphisms combined with risk factors of colorectal cancer (CRC) among selected Filipinos.
Methods. Genomic DNA isolated from peripheral blood samples of histologically confirmed CRC patients (n=70) and their age- and sex-matched clinically healthy controls (n=70) were analyzed for polymorphisms of XRCC1 and RAD51 genes by polymerase chain reaction.
Results. The genotypic distribution pattern of RAD51 135G>C (p˃0.05) was not significantly different between the CRC cases and controls. Significantly higher incidence (p=0.016) of the XRCC1 GG genotype was noted among the cases (n=34, 49%) compared with controls (n= 20, 29%). Individuals carrying the XRCC1 AG genotype have a lower risk of developing CRC (OR=0.42, 95% CI=0.21-0.85) than the XRCC1 GG genotype. XRCC1 AG genotype combined with alcohol drinking, smoking, or family history of cancer also showed a lower risk of developing CRC. There was no significant association between the genetic variants of RAD51 135G>C and CRC risk. Carriers of both XRCC1 GG and RAD51 CC genotypes showed a 5x higher risk (OR=5.02; 95%; CI=1.0429-24.1283) compared to those carrying other genotype combinations (p=0.028).
Conclusions. XRCC1 Arg399Gln but not RAD51 135G>C may be associated with CRC development among Filipinos. Individuals who drink alcohol, smoke tobacco and have a family history of cancer have a lower risk of developing CRC when they are also carrying the XRCC1 AG genotype. The findings may have significant impli cations in designing personalized methods for screening, diagnosing, and treating CRC.