Contribution of Xeroderma Pigmentosum Complementation Group C Genotypes to Colorectal Cancer in Taiwanese

Xeroderma pigmentosum complementation group C (XPC) is reported to play important roles in DNA integrity and genomic instability, however, the contribution of XPC to colorectal cancer (CRC) carcinogenesis is largely uncertain. Therefore, we aimed to examine the potential associations of XPC rs2228000 and rs2228001 genotypes and CRC susceptibility in a Taiwanese cohort.

A total of 362 patients with CRC and non-cancer controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. The distribution of genotypes and alleles was assessed, and conformity to Hardy-Weinberg equilibrium was checked.

Firstly, no statistically significant differences were observed in the genotypic frequencies of XPC rs2228000 and rs2228001 between patients with CRC and healthy controls (p for trend=0.5419 and 0.5005, respectively). Secondly, the allelic analyses revealed lack of associations with CRC risk regarding XPC rs2228000 T allele (odds ratio=0.89, 95% confidence interval=0.72-1.11, p=0.3446), and rs2228001 C allele (odds ratio=1.14, 95% confidence interval=0.92-1.41, p=0.2688). Interestingly, individuals carrying the CT or TT genotypes of XPC rs2228000 were prone to presenting metastatic behavior (p=0.0001). Moreover, individuals carrying the AC or CC genotypes of XPC rs2228001 were more likely to have larger tumor sizes (≥5 cm, p=0.0116), lymph node involvement (p=0.0014), advanced clinical stage (III-IV, p=0.0002), and metastasis (p=0.0002).

Although the investigated XPC polymorphisms were not associated with CRC susceptibility, the rs2228000 and rs2228001 variant genotypes may serve as novel prognostic biomarkers. Further large-scale studies across diverse populations are recommended to validate these findings.