Contribution of DNA repair xeroderma pigmentosum group D genotypes to pancreatic cancer risk in the Chinese Han population

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.

Associations of mRNA expression of DNA repair genes and genetic polymorphisms with cancer risk: a bioinformatics analysis and meta-analysis

“…Among those cSNPs, a few potential functional SNPs such as located in the 5'-untranslated regions (5'UTR) or Exon sites of the candidate genes could change the DNA repair capacity by regulating the transcriptional activity or protein expression, thereby playing critical roles in altering individual's susceptibility to cancer. Previous accumulating studies provided evidence about the association of SNPs in DNA repair gene with cancer risk, and most widely studied polymorphism including XPA rs2808668 19-26, rs10817938 21, 25, 26, XPC rs1870134 21, 22, 26-31, XPD rs238406 32-54, XPF rs3136038 39, 55-63, WRN rs1801195 64-67, rs1346044 64, 65, 68-75. The SNPs XPA rs10817938, XPA rs2808668 and XPF rs3136038 are all the polymorphisms in the site of the gene promoter.…”

Genetic polymorphisms and haplotypes of ERCC1 and ERCC2 associated with quality of life, depression, and anxiety status among patients with lung cancer

“…Previous studies on tumor susceptibility found that although single SNPs were not significantly associated with tumor risk, haplotypes containing one or more functional SNPs have significant associations with tumor susceptibility [ 13 ]. For example, two haplotypes containing the ERCC2 rs3916874 G allele were closely related to the risk of lung cancer, rs13181-rs3916874-rs238415 AGG haplotypes are associated with an increased risk of pancreatic cancer [ 28 ]. Studies on SNP and chemotherapy adverse reactions also found that the combination of genetic markers may be a better at-risk prediction [ 29 ].…”