Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer

Weiyan CHEN; Qi LONG; Lingqiao WANG; Menglong XIANG; Huan YANG; Jia CAO; Ziyuan ZHOU

doi:10.16016/j.1000-5404.201801212

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Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer

Clinical Medicine | 更新时间：2026-01-09

- Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer
- Journal of Third Military Medical University Vol. 40, Issue 10, Pages: 909-917(2018)
- 作者机构：
  
  1.400038 重庆，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
  2.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系：毒理学研究所
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81273156);the General Program of National Natural Science Foundation of China(30771841)
- DOI：10.16016/j.1000-5404.201801212
  CLC： R318.04;R394.3;R735.3
- Received：25 January 2018，
  
  Revised：2018-03-06，
  
  Published：30 May 2018
- 稿件说明：
移动端阅览
Weiyan CHEN, Qi LONG, Lingqiao WANG, et al. Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer[J]. Journal of Third Military Medical University, 2018, 40(10): 909-917.
DOI：

Weiyan CHEN, Qi LONG, Lingqiao WANG, et al. Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer[J]. Journal of Third Military Medical University, 2018, 40(10): 909-917. DOI： 10.16016/j.1000-5404.201801212.

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(

=4.89，95%

=1.29~18.51，

=0.020；OR

adj

=3.31，95%

=0.84~ 13.06，

adj

=0.087)和位点rs6891588 AG+GG基因型(

adj

=1.28，95%

=1.00~1.64，

adj

=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(

trend

=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(

分别为2.67、2.98，95%

分别为1.78~4.02、1.46~6.04，

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 (

=4.89

95%

: 1.29~18.51

=0.020;

adj

=3.31

95%

: 0.84~13.06

adj

=0.087) and rs6891588 AG+GG (

adj

=1.28

95%

: 1.00~1.64

adj

=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 (

trend

=0.004). The results of haplotype analysis showed that the haplotypes T_C_C_G_G_A_A (

=2.67

95%

: 1.78~4.02

0.001) and T_G_A_G_G_G_A (

=2.98

95%

: 1.46~6.04

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.

关键词

Keywords

references

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