Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk

Abstract

Purpose-Functional variation in DNA repair capacity through single nucleotide polymorphisms (SNPs) of key repair genes is associated with a higher risk of developing various types of cancer. Studies have focused on the nucleotide excision repair (NER) and base excision repair (BER) pathways. We investigated whether variant alleles in seven SNPs within these pathways increased the risk of esophageal adenocarcinoma. NIH Public Access Author ManuscriptCancer Causes Control. Author manuscript; available in PMC 2011 June 1. Results-Variant alleles in NER SNPs XPD Lys751Gln (AOR = 1.50, 95% CI 1.1-2.0), ERCC1 8092 C/A (AOR = 1.44, 95% CI 1.1-1.9), and ERCC1 118C/T (AOR = 1.42, 95% CI 1.0-1.9) were individually associated with esophageal adenocarcinoma risk. An increasing number of variant alleles in NER SNPs showed a significant trend with esophageal adenocarcinoma risk (p = 0.007).Conclusions-The presence of variant alleles in NER genes increases risk of esophageal adenocarcinoma. There is evidence of an additive role for SNPs along a common DNA repair pathway. Future larger studies of esophageal adenocarcinoma etiology should evaluate entire biological pathways.

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

“…Some previous studies showed a dose-response relationship between cancer risk and the number of variant alleles in both NER and BER. 33 In the study of Tse et al 47 an increased risk of esophageal adenocarcinoma was observed with the number of variant alleles. And Hu et al 48 also reported rising lung cancer risk associated with a combination of several variant alleles.…”

Meta-analysis demonstrates association of XRCC1 genetic polymorphism Arg399Gln with esophageal cancer risk in the Chinese population

“…Previous epidemiological studies demonstrated that nitrosamine carcinogens, cigarette smoking, alcohol drinking, and genetic polymorphisms might increase the risk of the disease (Gao et al, 1994;van Schooten et al, 1997;Yu et al, 2004). However, not all of those who have been exposed to the risk factors will develop EC, suggesting inter-individual differences in susceptibility.…”

Association Between XPD Asp312Asn Polymorphism and Esophageal Cancer Susceptibility: A Meta-analysis

“…Of the 45 records found initially, 8 case-control studies were included for this meta-analysis (Xing et al, 2002;Xing et al, 2003;Yu et al, 2004;Ye et al, 2006;Liu et al, 2007;Tse et al, 2008;Pan et al, 2009;Huang et al, 2012). A detailed flowchart of the selection process was showed in Figure 1.…”

“…The subjcets form 135 to 433 in case group while 152 to 524 in control group, comprising 2165 cases and 3141 controls. Four studies were conducted in China (Xing et al, 2002;Xing et al, 2003;Yu et al, 2004;Huang et al, 2012), three in the USA (Liu et al, 2007;Tse et al, 2008;Pan et al, 2009), and one in Sweden (Ye et al, 2006). In terms of source of control, all had a well matched, two was form hosptial-based (HB) (Yu et al, 2004;Huang et al, 2012), and 6 were population-based (PB) (Xing et al, 2002;Xing et al, 2003;Ye et al, 2006;Liu et al, 2007;Tse et al, 2008;Pan et al, 2009).…”

“…Four studies were conducted in China (Xing et al, 2002;Xing et al, 2003;Yu et al, 2004;Huang et al, 2012), three in the USA (Liu et al, 2007;Tse et al, 2008;Pan et al, 2009), and one in Sweden (Ye et al, 2006). In terms of source of control, all had a well matched, two was form hosptial-based (HB) (Yu et al, 2004;Huang et al, 2012), and 6 were population-based (PB) (Xing et al, 2002;Xing et al, 2003;Ye et al, 2006;Liu et al, 2007;Tse et al, 2008;Pan et al, 2009). The cancer type of 4 were ESCC (Xing et al, 2002;Xing et al, 2003;Yu et al, 2004;Huang et al, 2012), two were EADC (Liu et al, 2007;Tse et al, 2008), and 2 were both (Ye et al, 2006;Pan et al, 2009).…”