[1]陈维艳,龙琦,王灵巧,等.PC4基因启动子区多态性与结直肠癌发病风险的关联研究 [J].第三军医大学学报,2018,40(10):909-917.
 CHEN Weiyan,LONG Qi,WANG Lingqiao,et al.Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer[J].J Third Mil Med Univ,2018,40(10):909-917.
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PC4基因启动子区多态性与结直肠癌发病风险的关联研究
 
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第10期
页码:
909-917
栏目:
临床医学
出版日期:
2018-05-30

文章信息/Info

Title:
Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer
作者:
陈维艳龙琦王灵巧向梦龙杨桓曹佳周紫垣
陆军军医大学(第三军医大学)军事预防医学系:军事环境卫生学教研室,毒理学研究所
 
Author(s):
CHEN Weiyan LONG Qi WANG Lingqiao XIANG Menglong YANG Huan CAO Jia ZHOU Ziyuan

Department of Military Environmental Hygiene, Institute of Toxicology, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
结直肠癌人转录辅因子4单核苷酸多态性启动子区病例对照研究
Keywords:
colorectal cancer human positive cofactor/coactivator 4 single nucleotide polymorphismpromoter regioncase-control study
分类号:
R318.04;R394.3;R735.3
文献标志码:
A
摘要:

目的    通过对PC4基因启动子区潜在功能性SNP位点与结直肠癌的发病风险的关联分析,探索PC4基因遗传变异作为结直肠癌遗传易感性分子标记的可能性。方法    ①经生物信息学方法筛选PC4基因启动子区SNP位点;②采用探针法和测序法对选定SNP位点进行基因分型后于病例对照研究中作多因素Logistic回归分析。结果    ①筛选出PC4启动子区7个潜在功能性SNP位点;②位点rs116123859 CC+CT基因型(OR=4.89,95% CI=1.29~18.51,P=0.020;ORadj=3.31,95% CI=0.84~13.06,Padj=0.087)和位点rs6891588 AG+GG基因型(ORadj=1.28,95% CI=1.00~1.64,Padj=0.048)与结直肠癌的发病风险有关联,但效应微弱;③随个体携带的“风险”倾向基因型的数量增多,结直肠癌风险也有随之增加的趋势(Ptrend=0.004);④单倍型T_C_C_G_G_A_A、T_G_A_G_G_G_A患结直肠癌的风险是其他单倍型的2倍(OR分别为2.67、2.98,95% CI分别为1.78~4.02、1.46~6.04,P值分别为<0.001、0.003)。结论    PC4基因启动区单核苷酸多态性与结直肠癌的风险之间具有显著关联性,提示PC4基因启动子区多态性具有作为结直肠癌遗传易感性分子标记的潜能。

Abstract:

Objective    To analyze the association between potential functional single nucleotide polymorphisms (SNPs) in human positive coactivator 4 (PC4) gene promoter and the risk of colorectal cancer and assess the possibility of genetic variation of PC4 gene as a molecular marker of colorectal cancer predisposition. Methods    The potential SNPs in PC4 gene promoter were selected using bioinformatic method, and Sanger sequencing and Taqman RT-PCR were used for genotyping these selected SNPs. Logistic regression analysis was performed to analyze the association between these SNPs and the risk of colorectal cancer in a case-control study involving 488 pathologically confirmed patients with colorectal cancer and 894 age, gender, and residence-matched concurrent patients with non-malignant diseases. Results    Seven potential SNPs in PC4 gene promoter were selected, among which the SNP sites rs116123859 AG+GG (OR=4.89, 95%CI: 1.29~18.51, P=0.020; ORadj=3.31, 95%CI: 0.84~13.06, Padj=0.087) and rs6891588 AG+GG (ORadj=1.28, 95%CI: 1.00~1.64, Padj=0.048) were found to be associated with the risk of colorectal cancer, but the effect was weak. The individuals carrying more risk genotypes tended to have increasing risks of colorectal cancer (Ptrend=0.004). The results of haplotype analysis showed that the haplotypes T_C_C_G_G_A_A (OR=2.67, 95%CI: 1.78~4.02, P<0.001) and T_G_A_G_G_G_A (OR=2.98, 95%CI: 1.46~6.04, P<0.003) were associated an increased risk of colorectal cancer by 2 folds compared with the other haplotypes. Conclusion    SNPs of PC4 gene promoter are significantly associated with the risk of colorectal cancer and can serve as a potential molecular marker of the susceptibility to colorectal cancer.

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更新日期/Last Update: 2018-05-30