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.

Epistatic effect of TLR3 and cGAS‐STING‐IKKε‐TBK1‐IFN signaling variants on colorectal cancer risk

“…So far, genome‐wide association studies have reported ~100 risk loci for CRC highlighting new genes and pathways contributing to CRC susceptibility and suggesting roles for Hedgehog signaling, Krüppel‐like factors, Hippo‐YAP signaling, and immune function . Hua et al have also suggested that polymorphisms within xeroderma pigmentosum group C (XPC) and G (XPG) genes may affect CRC susceptibility through impairment of the nucleotide excision repair (NER) pathway …”

“…4,5 Hua et al have also suggested that polymorphisms within xeroderma pigmentosum group C (XPC) and G (XPG) genes may affect CRC susceptibility through impairment of the nucleotide excision repair (NER) pathway. 6,7 Moreover, chronic intestinal inflammation has long been recognized as a prominent CRC driver. 8 Patients affected by inflammatory bowel diseases (IBD), such as Crohn's disease or ulcerative colitis, have been reported to have an increased risk of CRC development.…”

Evaluation of the ERCC2 (Lys751Gln), MSH2 (gIVS12-6TC), RAD54 (Ala730Ala), XPC (Lys939Gln), XPG (Asp1104Hist), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms in the Ecuadorian population with retinoblastoma

“…In contrast with a meta-analysis that studied 679 cases of several types of cancer and 902 controls, the most prevalent allele was A with 0.62 [38], coinciding the allele frequency of the studied population. In a meta-analysis made in a Chinese population, the Lys939Gln polymorphism was significantly associated with the risk of CRC in the A/C heterozygous pattern (OR = 1.40, CI of 95% = 1.16-1.69; p < 0.05) [39]. Another research demonstrated that the patients with the C/C genotype have 2.09 times more risk of developing bladder cancer than normal A/A genotype [40].…”

Association between the miRNA‐149 rs2292832 T>C polymorphism and Kawasaki disease susceptibility in a southern Chinese population

“…A TIANamp Blood DNA Kit (Centrifugal column, Tiangen) was used to extract DNA from the blood samples according to the manufacturer's instructions . TaqMan real‐time PCR assays were set up in 384‐well plates containing positive and negative samples and were carried out in an ABI Q6 system (Applied Biosystems) to genotype the miRNA‐149 rs2292832 T>C polymorphism …”