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.

In plants, exposure to solar ultraviolet (UV) light is unavoidable, resulting in DNA damage. Damaged DNA causes mutations, replication arrest, and cell death, thus efficient repair of the damaged DNA is essential. A light-independent DNA repair pathway called nucleotide excision repair (NER) is conserved throughout evolution. For example, the damaged DNA-binding protein Radiation sensitive 4 (Rad4) in Saccharomyces cerevisiae is homologous to the mammalian NER protein Xeroderma Pigmentosum complementation group C (XPC). In this study, we examined the role of the Arabidopsis thaliana Rad4/XPC homologue (AtRAD4) in plant UV tolerance by generating overexpression lines. AtRAD4 overexpression, both with and without an N-terminal yellow fluorescent protein (YFP) tag, resulted in increased UV tolerance. YFP-RAD4 localized to the nucleus, and UV treatment did not alter this localization. We also used yeast two-hybrid analysis to examine the interaction of AtRAD4 with Arabidopsis RAD23 and found that RAD4 interacted with RAD23B as well as with the structurally similar protein HEMERA (HMR). In addition, we found that hmr and rad23 mutants exhibited increased UV sensitivity. Thus, our analysis suggests a role for RAD4 and RAD23/HMR in plant UV tolerance.