DNA repair genes XPC, XPG polymorphisms: Relation to the risk of colorectal carcinoma and therapeutic outcome with oxaliplatin‐based adjuvant chemotherapy

Abstract

Xeroderma pigmentosum complementation group C and G (XPC, XPG) play important roles in DNA damage repairing machinery. Genetic variations in the XPC and XPG may be associated with increased risk for colorectal carcinoma (CRC). In this study, we evaluated the relation between the XPC Lys939Gln, XPG Asp1104His polymorphisms, and CRC susceptibility in a population-based case-control study, which included 1,028 CRC cases and 1,085 controls. Compared with the corresponding wild genotypes, we found that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) and XPG Asp1104His (GC or CC genotype) had an increased risk for CRC. In addition, the variant genotypes of the XPC Lys939Gln AC/CC (P = 0.027) or XPG Asp1104His GC/CC (P = 0.003) reduced the elevation of preoperative carcinoembryonic antigen (CEA) level. Moreover a significantly longer progression-free survival (PFS) after Oxaliplatin-based adjuvant chemotherapy was observed in patients with XPG Asp1104His wide-type GG genotype (n = 432, Log-rank test: P = 0.033). Cox proportional hazards analyses demonstrated that variant genotypes of XPG Asp1104His [hazard ratio (HR) = 1.692, 95% confidence interval (95%CI): 1.202-2.383, P = 0.003] as well as pathology grade (HR = 2.545, 95%CI: 2.139-3.030, P < 0.001), and lymph node metastases (HR = 1.851, 95%CI: 1.306-2.625, P < 0.001) were predictive of shorter PFS for the CRC patients with Oxaliplatin-based adjuvant chemotherapy. In conclusion, the current data suggested that XPC Lys939Gln and XPG Asp1104His polymorphisms might contribute to the identification of patients with increased risk for CRC.

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

“…The additional functions of XPG are evident by the presence of structural motifis that are common with proteins involved in repair-recombination and cell cycle regulation (Klungland et al, 1999). It is reported that polymorphisms in XPG are associated with various cancers, such as colorectal cancer, esophageal cancer and lung cancer as well as bladder cancer (Chang et al, 2008;Pan et al, 2009;Rouissi et al, 2011;Liu et al, 2012). However, there was only one study conducted in Chinese population about the association between XPG and gastric cancer risk .…”

Associations of ABCB1 and XPC Genetic Polymorphisms with Susceptibility to Colorectal Cancer and Therapeutic Prognosis in a Chinese Population

“…Moreover, recent year studies have established that the polymorphisms in DNA repair genes can either change protein coding or alter the levels of transcription or translation, consequently, which can reduce DNA repair capacity and induce genetic instability or carcinogenesis. Few studies have investigated the associations between XPC Lys939Gln and risk of CRC, and these findings were inconsistent (Hansen et al, 2007;Engin et al, 2010;Wu et al, 2011;Liu et al, 2012). Overall, the XPC Lys939Gln was found to be associated with CRC risk in two case-control studies (Wu et al, 2011;Liu et al, 2012) while others did not find any statistically significant associations (Hansen et al, 2007;Engin et al, 2010).…”

“…Few studies have investigated the associations between XPC Lys939Gln and risk of CRC, and these findings were inconsistent (Hansen et al, 2007;Engin et al, 2010;Wu et al, 2011;Liu et al, 2012). Overall, the XPC Lys939Gln was found to be associated with CRC risk in two case-control studies (Wu et al, 2011;Liu et al, 2012) while others did not find any statistically significant associations (Hansen et al, 2007;Engin et al, 2010). In this study, although there were no statistically significant association observed between XPC Lys939Gln polymorphism and CRC risk, it is worth to note that current data regarding XPC Lys939Gln polymorphism showed a tendency for a higher risk of developing CRC in heterozygous AC genotypes (P=0.0759) or AC+CC variants carriers (P=0.0903).…”

“…Previously studies have shown that polymorphisms of the NER pathway genes may alter the DNA repair capacity and thus could play an important role in carcinogenesis (Friedberg, 2001). Only few studies have investigated the association of Lys 939Gln polymorphism of XPC with CRC risk, and the findings were inconclusive (Hansen et al, 2007;Engin et al, 2010;Wu et al, 2011;Liu et al, 2012). Wu et al found that the XPC Lys939Gln CC genotype was associated with a significantly increased risk of CRC compared with the AA genotype (Wu et al, 2011).…”

“…Wu et al found that the XPC Lys939Gln CC genotype was associated with a significantly increased risk of CRC compared with the AA genotype (Wu et al, 2011). Similarly, Liu et al observed that individuals with at least one copy of the XPC Lys939Gln (AC or CC genotype) had an increased risk for CRC (Liu et al, 2012). However, in Denmark population, there are no significant association oberved between Lys939Gln and CRC risk, whereas they found a significant interaction between Lys939Gln and consumption of red meat, with a 3.7-fold increase in CRC risk per 100 g red meat intake per day among carriers of the homozygous variant, but virtually no effect of red meat intake among carriers of the wild type allele (Hansen et al, 2007).…”