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Title: [Correlation of XPC Ala499Val and Lys939Gln polymorphisms to risks of esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].
Author: Zhou RM, Li Y, Wang N, Zhang XJ, Dong XJ, Guo W.
Journal: Ai Zheng; 2006 Sep; 25(9):1113-9. PubMed ID: 16965652.
Abstract:
BACKGROUND & OBJECTIVE: Xeroderma pigmentosum group C(XPC) gene is involved in nucleotide excision repair (NER). Single nucleotide polymorphisms (SNP) in XPC gene may affect DNA repairing capacity and genetic susceptibility to cancer. This study was to investigate the correlation of XPC exon 8 Ala499Val and exon 15 Lys939Gln SNPs to the susceptibility of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population at a high incidence region of Hebei Province. METHODS: XPC exon 8 Ala499Val and exon 15 Lys939Gln SNPs were genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis in 327 ESCC patients, 253 GCA patients, and 612 healthy controls. RESULTS: The number of the subjects with family history of upper gastrointestinal cancer (UGIC) was significantly higher in ESCC and GCA groups than in control group. Family history of UGIC may increase the risk of developing ESCC and GCA [age and gender adjusted odds ratio (OR) =1.76 and 1.77, 95% confidence interval (CI) = 1.34-2.32 and 1.31-2.39]. The overall allelotype and genotype distributions of XPC exon 8 Ala499Val in ESCC patients were not significantly different from those in healthy controls (P>0.05). T allelotype frequency of XPC exon 8 in GCA patients was 26.5%, which was significantly lower than that in healthy controls (Chi2=6.12, P=0.01). The C/T genotype frequencies of XPC exon 8 in GCA patients and healthy controls were 35.6% and 46.1% respectively. Compared with individuals with C/C genotype, individuals with C/T genotype had significantly lower risk in developing GCA (OR=0.62, 95% CI=0.45-0.84). When stratified for smoking status and family history of UGIC, compared with individuals with C/C genotype, individuals with C/T genotype in smoker group and in the group without family history of UGIC had lower risk in developing GCA (OR=0.57, 95% CI=0.36-0.91 and 0.37-0.88). The overall allelotype and genotype distributions of XPC exon 15 Lys939Gln in ESCC and GCA patients were not significantly different from those in healthy controls (P>0.05). When stratified for smoking status and family history of UGIC, compared with individuals with A/A genotype, individuals in non-smoker group with C/C genotype had higher risk in developing ESCC (OR=2.05, 95% CI=1.15-3.66). The haplotype distribution of ESCC patients was not significantly different from that of healthy controls (P>0.05), while the haplotype distribution of GCA patients was significantly different from that of healthy controls (P=0.02). Compared with A/T haplotype, A/C and C/C haplotypes significantly increased the risk of developing GCA (OR=1.35 and 1.46, 95% CI=1.01-1.81 and 1.06-2.00). CONCLUSIONS: In the high incidence region of Hebei Province, C/T genotype of XPC exon 8 may decrease the risk of developing GCA. Lys939Gln SNP in exon 15 may have no influence on the risk of ESCC and GCA, but when stratified for smoking status, C/C genotype of XPC exon 15 may increase the risk of developing ESCC in non-smoking population. While A/C and C/C haplotypes may increase the risk of developing GCA.

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