天津地区人群hMLH1和hMSH2基因多态性与散发性结直肠癌易感性的关系

doi:10.3724/SP.J.1005.2010.01241

遗传 ›› 2010, Vol. 32 ›› Issue (12): 1241-1246.doi: 10.3724/SP.J.1005.2010.01241

天津地区人群hMLH1和hMSH2基因多态性与散发性结直肠癌易感性的关系

李会晨¹,冯会媛²,张锡朋¹,刘蕊³,马东旺¹,秦海¹,周毅¹,俞林

1. 天津市人民医院肛肠外科, 天津 300121;
2. 天津市医学高等专科学校, 天津 300222;
3. 天津市人民医院检验科, 天津 300121

收稿日期:2010-02-09 修回日期:2010-04-26 出版日期:2010-12-20 发布日期:2010-12-20
通讯作者: 李会晨 E-mail:lihuichen_tianjin@yahoo.com.cn
基金资助:
天津市卫生局科技基金项目(编号：07KG11)资助

Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region

LI Hui-Chen¹, FENG Hui-Yuan², ZHANG Xi-Peng¹, LIU Rui³, MA Dong-Wang¹, QIN Hai¹, ZHOU Yi¹, YU Lin¹

1. Department of Anus & Intestine Surgery, Tianjin People’s Hospital, Tianjin 300121, China;
2. Tianjin Medical College, Tianjin 300222, China;
3. Department of Clinical Laboratory, Tianjin People’s Hospital, Tianjin 300121, China

Received:2010-02-09 Revised:2010-04-26 Online:2010-12-20 Published:2010-12-20
Contact: LI Hui-Chen E-mail:lihuichen_tianjin@yahoo.com.cn

摘要/Abstract

摘要： 为探讨错配修复基因hMLH1和hMSH2 单核苷酸多态性(Single nucleotide polymorphism, SNP)与散发性结直肠癌(Sporadic colorectal caner, SCRC)发病易感性之间的关系, 文章采用聚合酶链式反应-变性高效液相色谱方法和序列分析技术, 检测了天津地区600例SCRC患者和600例健康对照个体hMLH1 394G/C、hMSH2 943-1G/A、hMSH2 1917T/G和hMSH2 2783C/A的基因型频率分布。结果显示: SCRC患者组hMSH2 2783C/A 3种基因型C/C、C/A、A/A频率(90%、9% 、1%)与对照组(95%、4.8%、0.2%)相比差异具有统计学意义(χ²=11.91, P<0.01)。与hMSH2 2783C/C基因型相比, C/A和A/A基因型能增加SCRC发病风险(OR值分别为1.77和11.94, 95%CI分别为1.03~3.03和1.38~103.2)。多态性位点联合分析显示, SCRC组与对照组单倍型分布差异有统计学意义(χ²=38.38, P<0.01); 与394G/943-1G/2783C单倍型相比, 394G/943-1G/2783A单倍型显著增加SCRC的发病风险(OR=2.18, 95%CI: 1.40~3.40)。结果提示hMSH2 2783C/A多态性可能成为预测SCRC发病风险的独立因素, 394G/943-1G/2783A单倍型可能增加SCRC的发病风险。

关键词: hMSH2, 单核苷酸多态性, 散发性结直肠癌, 发病易感性, 单倍型, hMLH1

Abstract: To investigate the possible association of mismatch repair gene single nucleotide polymorphisms (SNPs) with susceptibility to sporadic colorectal cancer (SCRC), the genotypes of hMLH1 394G/C, hMSH2 943-1G/A, hMSH2 1917T/G, and hMSH2 2783C/A were detected by PCR-denaturing high-performance liquid chromatography (DHPLC) in 600 SCRC patients and 600 healthy controls. The genotype distribution of hMSH2 2783C/A in SCRC patients (90%, 9%, and 1%) was significantly different from that in the controls (95%, 4.8%, and 0.23%; χ²=11.91, P<0.01). Compared to hMSH2 2783C/C, genotypes C/A and A/A significantly increased the risk of developing SCRC (OR were 1.77 and 11.94, and the reanges of 95% CI were 1.03-3.03 and 1.38-103.2). When combined analysis of three SNPs was performed, the haplotype distribution in SCRC patients was significantly different from that in controls (χ²=38.38, P<0.01). In reference to 394G/943-1G /2783C haplotype, 394G/943-1G /2783A haplotype contributed significantly to SCRC (OR=2.18, 95% CI: 1.40-3.40). These results indicate that hMSH2 2783C/A polymorphism has potential to be a susceptibility factor for SCRC and the 394G/943-1G /2783A haplotype might increase the risk of developing SCRC.

Key words: hMLH1, hMSH2, single nucleotide polymorphisms, sporadic colorectal cancer, susceptibility, haplotype

李会晨，冯会媛，张锡朋，刘蕊，马东旺，秦海，周毅，俞林. 天津地区人群hMLH1和hMSH2基因多态性与散发性结直肠癌易感性的关系[J]. 遗传, 2010, 32(12): 1241-1246.

LI Hui-Chen, FENG Hui-Yuan, ZHANG Ti-Peng, LIU Juan, MA Dong-Wang, QIN Hai, ZHOU Yi, SHU Lin. Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region[J]. HEREDITAS, 2010, 32(12): 1241-1246.

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天津地区人群hMLH1和hMSH2基因多态性与散发性结直肠癌易感性的关系

Association of mismatch repair gene polymorphism with susceptibility to sporadic colorectal cancer in Tianjin region

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