Association of XPC Gene Polymorphisms with Colorectal Cancer Risk in a Southern Chinese Population: A Case-Control Study and Meta-Analysis

Abstract

Xeroderma pigmentosum group C (XPC) is a key component of the nucleotide excision repair (NER) pathway. Dysfunctional XPC protein may impair NER-mediated DNA repair capacity and further lead to genomic instability and carcinogenesis. Two common nonsynonymous polymorphisms in the XPC gene, Lys939Gln (rs2228001 A > C) and Ala499Val (rs2228000 C > T), have been investigated in various types of cancer. We genotyped these two polymorphisms in 1141 cases with histologically confirmed colorectal cancer (CRC) and 1173 healthy controls to explore their causative association with CRC susceptibility. Overall, no association was observed between these two variants and the risk of CRC. Our meta-analysis also confirmed a lack of overall association. Stratified analyses were performed by age, gender, smoking status, pack-year, drinking status, tumor sites, and Duke's stages. We found that XPC Lys939Gln polymorphism was significantly associated with an increased CRC risk in subjects at 57 years of age or younger (adjusted odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.004-1.86, p = 0.047) and non-drinkers (adjusted OR = 1.53, 95% CI = 1.10-2.12, p = 0.011). Our results indicated that XPC Lys939Gln may be a low-penetrance CRC susceptibility polymorphism. Our findings warrant further validation.

Keywords: DNA repair; XPC; colorectal cancer; genetic susceptibility; polymorphism.

Figure 1

Forest plot of effect estimates for xeroderma pigmentosum group C (XPC) rs2228001 A > C polymorphism with overall colorectal cancer risk by a recessive model. For each study, the estimates of odds ratio (OR) and its 95% confidence interval (CI) are plotted with a box and a horizontal line. ◊, pooled ORs and its 95% CIs.

Figure 2

Forest plot of effect estimates for XPC rs2228000 C > T polymorphism with overall colorectal cancer risk by a recessive model. For each study, the estimates of OR and its 95% CI are plotted with a box and a horizontal line. ◊, pooled ORs and its 95% CIs.