Genetic susceptibility to esophageal cancer: the role of the nucleotide excision repair pathway

Abstract

In this case-control study with 387 White esophageal patients and 462 White controls matched to cases by age and sex, we evaluated the associations between 13 potential functional polymorphisms in eight major nucleotide excision repair (NER) genes and esophageal cancer risk. In individual single nucleotide polymorphism analysis, after adjustment for multiple comparisons, the heterozygous GT genotype of the ERCC1 3' untranslated region (UTR) was associated with an increased risk, whereas the homozygous variant genotype TT was associated with 60% reduction in risk with an odds ratio (OR) of 0.40 (95% confidence interval [CI] = 0.19-0.86). The heterozygous AG genotype of XPA 5' UTR was at 2.11-fold increased risk (95% CI = 1.33-3.35) and the risk reached 3.10-fold (95% CI = 1.94-4.95) for the homozygous variant GG genotype. These associations were also significant when restricted the analyses in patients with esophageal adenocarcinoma. Further, the CT genotype of the RAD23B Ala249Val was associated with increased esophageal cancer risk (OR = 1.44; 95% CI = 1.05-1.97), whereas the poly-AT-/+ genotype of the XPC intron 9 conferred a decreased risk (OR = 0.71, 95% CI = 0.51-0.97). In joint analysis, individuals carrying 1 (OR = 2.64, 95% CI = 1.57-4.52) and > or = 2 (OR = 2.74, 95% CI = 1.58-4.75) unfavorable genotypes exhibited significantly increased risk for esophageal cancer risk with significant dose-response trend (P for trend = 0.006). The pathway-based risk was more evident in ever smokers, overweight/obese individuals, men and ever drinkers. Our results support the hypothesis that increasing numbers of unfavorable genotypes in the NER predispose susceptible individuals to increased risk of esophageal cancer. These findings warrant further replications in different populations.

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 .…”

Genetic variation of XPA gene and risk of cancer: A systematic review and pooled analysis

“…5 To date, a number of molecular epidemiological studies have been done to evaluate the association between XPA À4G>A polymorphism and different types of cancer risk in diverse populations. The tumor types included lung cancer, 6,13,22,24,[29][30][31][32][33][34] gastric cancer, 7,17 colorectal cancer, 8,12,23 squamous cell carcinoma of the head and neck, 8,10 basal and squamous cell carcinomas of the skin (BCC and SCC), 20,27 breast cancer, 8,18,26 esophageal cancer, 11,14,15 and so on. However, the results were inconsistent or even contradictory.…”

XPD Lys751Gln Polymorphisms and the Risk of Esophageal Cancer: An Updated Meta-Analysis

“…1. Two cancer types were included in the studies by Pan and Ye; therefore, there were 21 case-control studies in this meta-analysis (23,28). As shown in Table 1, there were 14 case-control studies, including 3,457 cancer cases and 4,855 controls, of the XPD Lys751Gln polymorphism and ESCC risk and seven studies, including 1,726 cases and 3,396 controls, of the XPD Lys751Gln polymorphism and EADC risk.…”