Genetic susceptibility of gastric cancer with single nucleotide polymorphisms(SNPs) of apoptotic genes - caspase-3 and caspase-7 / 实用肿瘤学杂志

ABSTRACT

Objective The SNPs of caspase family have been studied in breast cancer,head and neck cancer,esophageal cancer,lung cancer and other cancer. There are few studies between the SNP of CASP3,7 and the risk of gastric cancer in Chinese population. The aim of this study was to investigate the relationship between the SNP of CASP3,7 genes and the genetic susceptibility of gastric cancer using large samples. Methods Blood samples from 1000 cases of gastric cancer and 1036 cases of normal non-cancer control in Northeast China were collected for genomic DNA extraction. Based on the dbSNP NCBI database and HapMap data-base,potential SNP sites were selected for CASP3,7,which locate CASP3,CAS′s 3′UTR. The Tasman probe method was used for gen-otyping of the SNP sites of CASP3,7. The difference between the different variables in the case-control group was analyzed by the bi-lateral χ2 test. After the Hardy-Weinberg genetic balance test for each locus,the χ2 test was used to compare the genotype frequency differences between the case and control groups. Univariate and multivariate logistic regression models were used to analyze the associ-ation between genotype and disease. The stratification analysis of each locus compared the genotypes between the different sexes,ages, smoking,and drinking status. Results The χ2 test compared the differences between the case and control groups. The results showed that there was a significant difference in the smoking,drinking status and smoking in packet number( Pack-years) between the case and control groups(P<0. 05). The genotype frequencies of selected loci were in accordance with Hardy-Weinberg′s law of genetic balance(P>0. 05). Combining and analyzing genotypes with risk alleles,there showed that individuals with two risk genotypes in- creased by 69. 6% in comparison with individuals with 0~1 risk genotype. After adjusted for covariate effects,individuals with three risk genotypes were increased by 27. 6% when compared to individuals with 0~1 risk genotypes. Individuals with more than one risk genotype were increased by 35% when compared to individuals with 0-1 risk genotypes. In the stratified analysis,after combination of two genes,the risk genotype in the sub-layer of age ≤60 years old,male,never smoking,annual smoking package ≤25,gastric non-cardiac adenocarcinoma was statistically associated with disease,i. e. more risk of gastric cancer. Conclusion Univariate analy-sis showed that the SNPs at the four sites selected in this study were not associated with the risk of gastric cancer. However,multivari-ate analysis of CASP3 and CASP7 at the four sites showed that individuals with two risk genotypes increased the risk of gastric cancer in comparison with individuals with 0~1 risk genotypes. In addition,after stratified analysis of the two sites of CASP7,the risk of gas-tric cancer is more obvious in people aged≤60 years,never smoking or smoking≤25 packs per year,and non-gastric cardia adeno-carcinoma.