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同源重组修复通路基因遗传变异与结直肠癌易感性的关联研究
Association between polymorphisms of homologous recombination repair pathway genes and the risk of colorectal cancer
- 第三军医大学学报 2019年41卷第18期 页码：1769-1775
- 作者机构：
1.550025 贵阳，贵州医科大学公共卫生学院
2.400038 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
3.400038 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：
[ 周紫垣，E-mail:ziyuanzhou@tmmu.edu.cn ZHOU Ziyuan, E-mail:ziyuanzhou@tmmu.edu.cn
[ 张爱华，E-mail:aihuagzykd@163.com ZHANG Aihua, E-mail: aihuagzykd@163.com
- 基金信息：国家自然科学基金面上项目(81273156);国家自然科学基金面上项目(30771841)
DOI：10.16016/j.1000-5404.201905200
中图分类号： R181.24;R394.3;R735.35收稿：2019-05-25，
修回：2019-07-15，
纸质出版：2019-09-30
- 稿件说明：
移动端阅览
禚昌龙, 陈维艳, 龙琦, 等. 同源重组修复通路基因遗传变异与结直肠癌易感性的关联研究[J]. 第三军医大学学报, 2019,41(18):1769-1775.
Changlong ZHUO, Weiyan CHEN, Qi LONG, et al. Association between polymorphisms of homologous recombination repair pathway genes and the risk of colorectal cancer[J]. Journal of Third Military Medical University, 2019, 41(18): 1769-1775.
禚昌龙, 陈维艳, 龙琦, 等. 同源重组修复通路基因遗传变异与结直肠癌易感性的关联研究[J]. 第三军医大学学报, 2019,41(18):1769-1775. DOI： 10.16016/j.1000-5404.201905200.
Changlong ZHUO, Weiyan CHEN, Qi LONG, et al. Association between polymorphisms of homologous recombination repair pathway genes and the risk of colorectal cancer[J]. Journal of Third Military Medical University, 2019, 41(18): 1769-1775. DOI： 10.16016/j.1000-5404.201905200.
摘要
目的
2
探讨我国人群同源重组修复(homologous recombination repair，HRR)通路关键基因的单核苷酸多态性与结直肠癌(colorectal cancer，CRC)易感性关联。
方法
2
以生物信息学分析结合文献筛选同源重组修复通路关键基因；采用基于通路分析的病例-对照研究设计，共纳入2001年1月至2004年6月于陆军军医大学3所附属医院普通外科经病理诊断的413例新发CRC病例与1 671例非肿瘤患者对照。以ILLUMINA人类基因组芯片对筛选出的基因上下游50 kb区域内的TagSNPs分型，采用logistic回归模型计算SNPs与CRC的关联。
结果
2
筛选出17个HRR通路中的关键基因；在17个基因及上下游50 kb区域内的2 207个SNP中有16个位点与结直肠癌风险关联显著，其中RAD52基因3’-UTR的rs11226位点携带A等位基因者的CRC风险相对携带G者增加约1.4倍(
OR
=1.42，95%
CI
=1.22~1.66，
P
=6.67×10
-6
)；CRTC3-AS1基因内含子区rs75893366位点携带G等位基因者的CRC风险仅为
携带A者的0.4倍(
OR
=0.43，95%
CI
=0.25~0.74，
P
=1.81×10
-3
)。但仅rs11226位点经bonferroni校正后在男性和女性中均具有显著性。
结论
2
同源重组修复通路中17个关键基因的单核苷酸多态性与结直肠癌患病风险显著关联，提示同源重组修复通路基因的遗传变异可能影响结直肠癌的遗传易感性。
Abstract
Objective
2
To investigate the association of single nucleotide polymorphisms (SNPs) of homologous recombination repair (HRR) pathway genes with the genetic susceptibility of colorectal cancer (CRC) in Chinese population.
Methods
2
Bioinformatics database analysis combined with literature screening was used to identify the key genes involved in the HRR pathway. Following a pathway-based case-control study design
413 patients with CRC and 1 671 cancer-free controls were recruited from 3 affiliated hospitals of the Army Military Medical University. TagSNPs of the selected genes and 50 kb of their upstream and downstream regions were genotyped using ILLUMINA human genome chip. Conditional logistic regression analysis was used to evaluate the association between the SNPs and the risk of CRC.
Results
2
Seventeen key genes in the HRR pathway were selected based on literature screening and bioinformatics database analysis. Sixteen of the total of 2207 genotyped SNPs were found significantly associated with the risk of CRC
among them the allele A at rs11226 of RAD52 3'-UTR was associated with an 1.4-fold higher risk of CRC than the allele G (
OR
=1.42
95%
CI
: 1.22~1.66
P
=6.67×10
-6
)
and the allele G at rs75893366 of CRTC3-AS1 gene was associated with a 0.43-fold lower risk of CRC than allele A (
OR
=0.43
95%
CI
: 0.25~0.74
P
=1.81×10
-3
). But after Bonferroni correction
only the SNP of rs11226 showed significant differences in both male and female patients in stratified analysis.
Conclusion
2
The 17 SNPs of the key genes in the HHR pathway are significantly associated with the risk of CRC
suggesting that the variations in HHR pathway genes contribute to the genetic susceptibility of CRC.
关键词
Keywords
references
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