Polymorphisms of the DNA repair gene xeroderma pigmentosum groups A and C and risk of esophageal squamous cell carcinoma in a population of high incidence region of North China

Abstract

Aim: Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity (DRC) and genetic susceptibility to different cancers. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum group A (XPA) and XPC can influence the risk of esophageal squamous cell carcinoma (ESCC).

Methods: In this report, one SNP of XPA and three SNPs of XPC were genotyped by polymerase-chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) assay in 327 ESCC patients and 612 healthy controls in a high incidence region of North China.

Results: Family history of upper gastrointestinal cancers (UGIC) may increase the risk of developing ESCC. The overall genotype and allelotype distributions of XPA A23G in ESCC patients were significantly different from that in healthy controls (P < 0.05). The A/G + G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype. When stratified for family history of UGIC, compared with A/A genotype, A/G + G/G genotype significantly decreased the risk of ESCC in groups with negative history of UGIC. The overall genotype and allelotype distributions of XPC intron 9 PAT(+/-) and exon 15 Lys939Gln and exon 8 Val499Ala in ESCC patients were not significantly different from that in healthy controls (P > 0.05). When stratified for smoking status and UGIC family history, compared with A/A genotype, C/C genotype of exon 15 Lys939Gln significantly increased the risk of developing ESCC in non-smoker group.

Conclusions: We concluded that XPA23 polymorphism may be useful markers for identifying individuals at risk of developing ESCC. C/C genotype of XPC exon 15 may be one of the factors that affect the risk of developing ESCC in nonsmoking population in the high incidence region of China.

Fig. 1

XPA A23G genotype 1: G/G genotype; 2,5:A/A genotype; 3,4,6,7: A/G genotype; 8: negative control; 9: 100 bp DNA marker

Fig. 2

XPC PAT^+/− genotype 1,3,6: +/− genotype; 2:+/+ genotype; 4,5: −/− genotype; 7: negative control; 8: 100 bp DNA marker

Fig. 3

XPC Ala499Val genotype 1: 100 bp DNA marker; 2,4,8: T/T genotype; 3,6,9,10,11: C/C genotype; 5,7,12: C/T genotype

Fig. 4

XPC Lys939Gln genotype 1:100 bp DNA marker; 2,8: A/C genotype; 3,4,10: C/C genotype; 5,6,7,9: A/A genotype