凋亡基因Caspase3和Caspase7单核苷酸多态性与胃癌遗传易感性研究

doi:10.11904/j.issn.1002-3070.2019.03.011

实用肿瘤学杂志 ›› 2019, Vol. 33 ›› Issue (3): 250-255.doi: 10.11904/j.issn.1002-3070.2019.03.011

凋亡基因Caspase3和Caspase7单核苷酸多态性与胃癌遗传易感性研究

刘佳音¹,燕飞虎²,张艳桥¹

1.哈尔滨医科大学附属肿瘤医院(哈尔滨 150081);
2.海南省肿瘤医院

收稿日期:2019-03-06 修回日期:2019-04-09 出版日期:2019-06-20 发布日期:2019-06-18
通讯作者: 张艳桥,E-mail:yanqiaozhang@126.com
作者简介:刘佳音,女,(1989-),硕士,住院医师,从事消化系统及胸部肿瘤的研究

Genetic susceptibility of gastric cancer with single nucleotide polymorphisms(SNPs)of apoptotic genes - caspase-3 and caspase-7

LIU Jiayin¹,YAN Feihu²,ZHANG Yanqiao¹

1.Harbin Medical University Cancer Hospital,Harbin 150081,China;
2.Hainan Cancer Hospital

Received:2019-03-06 Revised:2019-04-09 Online:2019-06-20 Published:2019-06-18

摘要/Abstract

摘要： 目的 Caspase家族的SNP在乳腺癌、头颈部肿瘤、食管癌、肺癌等癌症中研究较多,而Caspase3,7的SNP与中国人群胃癌发病风险之间的研究较少。本实验旨在利用大样本研究Caspase3和Caspase7基因的SNP与胃癌遗传易感性的关系。方法收集东北地区胃癌病例1 000例、对照组1 036例血液标本,进行基因组DNA提取。根据NCBI的dbSNP数据库和HapMap数据库,对Caspase 3,7选择潜在的SNP位点,所选位点均位于Caspase3,Caspase7的3′UTR。对Caspase 3,7的SNP位点运用Taqman探针法进行基因型分型。病例对照之间不同变量构成比差异采用双侧χ²检验,对每个位点进行Hardy-Weinberg遗传平衡检验后,采用χ²检验比较病例组和对照组的单个位点基因型频率差异,再通过单因素和多因素Logistic回归模型分析基因型与疾病的关联,对每个位点分层分析比较不同性别、年龄、吸烟、饮酒状况亚层之间基因型与疾病的关联。结果病例组与对照组的吸烟、饮酒状态以及年吸烟包数(Pack-years)构成存在统计学差异(P＜0.05)。所选位点基因型频率符合Hardy-Weinberg遗传平衡定律(P＞0.05)。将带有风险等位基因的基因型组合后进行分析,显示出针对两个基因来说,带有两个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了69.6%,调整了协变量影响后带有3个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了27.6%,带有大于1个风险基因型的个体比带有0~1个风险基因型的个体患病风险增加了35%。两个基因组合之后的分层分析中,年龄≤60岁、男性、从不吸烟、年吸烟包数≤25、胃非贲门腺癌的亚层中风险基因型与疾病有统计学关联,即具有更显著的危险性。结论本研究所选取的四个位点的SNP均与胃癌风险无关。但通过多因素分析Caspase3、Caspase7的四个位点,带有2个风险基因型比带有0~1个风险基因型的个体患病风险增加。此外,通过分层分析Caspase7的两个位点,其在年龄≤60岁,从不吸烟,年吸烟包数≤25包和非胃贲门腺癌人群中患病风险更为明显。

关键词: 凋亡基因, 单核苷酸多态性, 胃癌, 遗传易感性

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 database,potential SNP sites were selected for CASP3,7,which locate CASP3,CAS′s 3′UTR.The Tasman probe method was used for genotyping of the SNP sites of CASP3,7.The difference between the different variables in the case-control group was analyzed by the bilateral 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 association 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 increased 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 analysis showed that the SNPs at the four sites selected in this study were not associated with the risk of gastric cancer.However,multivariate 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 gastric cancer is more obvious in people aged ≤60 years,never smoking or smoking ≤25 packs per year,and non-gastric cardia adenocarcinoma.

Key words: Apoptotic gene, Single nucleotide polymorphism, Gastric cancer, Genetic susceptibility

中图分类号:

R735.2

刘佳音,燕飞虎,张艳桥. 凋亡基因Caspase3和Caspase7单核苷酸多态性与胃癌遗传易感性研究[J]. 实用肿瘤学杂志, 2019, 33(3): 250-255.

LIU Jiayin,YAN Feihu,ZHANG Yanqiao. Genetic susceptibility of gastric cancer with single nucleotide polymorphisms(SNPs)of apoptotic genes - caspase-3 and caspase-7[J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(3): 250-255.

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凋亡基因Caspase3和Caspase7单核苷酸多态性与胃癌遗传易感性研究

Genetic susceptibility of gastric cancer with single nucleotide polymorphisms(SNPs)of apoptotic genes - caspase-3 and caspase-7

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