Abstract
This study aimed to determine the association between the polymorphisms and haplotypes in the xeroderma pigmentosum group D (XPD) gene and the risk of pancreatic cancer in the Chinese Han population. SNaPshot was used for genotyping six SNP sites of the XPD gene. Comparisons of the correlations between different genotypes in combination with smoking and the susceptibility to pancreatic cancer were performed. Individual pancreatic cancer risk in patients who carry mutant C alleles (AC, CC, and AC+CC) at rs13181 increased (p < 0.05). Taking non-smoking individuals who carry the AA genotype as a reference, and non-smoking individuals who carry mutant allele C (AC+CC), the risk of pancreatic cancer increased by 3.343 times in individuals who smoked ≥ 20 cigarettes daily, 3.309 times in individuals who smoked ≥ 14 packs per year, 5.011 times in individuals who smoked ≥ 24 packs per year, and 4.013 times in the individuals who smoked ≥ 37 packs per year (P < 0.05). In addition, haplotype analysis revealed that haplotype AGG, which comprised rs13181, rs3916874 and rs238415, was associated with a 1.401-fold increase in pancreatic cancer risk (p < 0.05). We conclude that the polymorphism of XPD Lys751Gln (rs13181) in combination with smoking contributes to increased risk of pancreatic cancer in the Chinese Han population. Haplotype AGG might be a susceptibility haplotype for pancreatic cancer.
Highlights
Pancreatic cancer (PC) is highly malignant, has an insidious onset, and lacks early diagnostic methods
The risk of PC did not increase in smokers compared with non-smokers (OR=1.384, 95% confidence intervals (CIs)=0.896-2.259, p=0.150), but the risk of PC increased in patients whose daily smoking amount was more than 20 cigarettes (OR=1.569, 95% CI=1.005-2.448, p=0.047)
The polymorphisms of xeroderma pigmentosum group D (XPD) Lys751Gln and Asp312Asn had no relationship with the susceptibility of non-Hodgkin’s lymphoma (Chen et al, 2015), and meta-analysis results revealed that the polymorphism of XPD Lys751Gln was not associated with the risk of liver cancer (Zhang and Mou, 2013)
Summary
Pancreatic cancer (PC) is highly malignant, has an insidious onset, and lacks early diagnostic methods. It has been reported that mutations of the XPD gene diminish its helicase activity, resulting in defective NER capacity for bulky DNA adducts and transcriptional activity, and in an abnormal response to apoptosis (Taylor et al, 1997). The most widely investigated XPD polymorphism in association with cancer susceptibility comprise a non-synonymous A to C substitution in exon 23 causing a lysine (Lys) to glutamine (Gln) substitution in codon 751 (Lys751Gln, rs13181) (Shen et al, 1998; Benhamou and Sarasin, 2002). The variant genotypes are both associated with lower DNA repair capacity and a higher level of DNA adducts left in the genome (Shen et al, 1998; Lunn et al, 2000; Benhamou and Sarasin, 2002). The results of these reports remain inconclusive and none investigated the Chinese Han population, which is genetically conservative and different from Western populations
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