结肠癌易感性与细胞毒性T淋巴细胞相关抗原4的关系

Association of cytotoxic T lymphocyte antigen-4 gene polymorphism with susceptibility on colorectal cancer

目的:探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因外显子49位点及启动子1661位点单核苷酸多态性(SNP)及临床病理参数与青岛地区人群结肠癌的发病的关系。方法:采用聚合酶链反应-限制性片段长度多态分析(PCR-RFLP)检测来自青岛地区人群结肠癌患者及对照组中位CT-LA-4+49A/G,-1661A/G基因多态性的分布,并研究多态性与结肠癌临床病理参数的关系。结果:1)CT-LA-4+49A/G:与AA基因型携带者相比,AG及GG基因型人群罹患结肠癌的风险都显著增加(P=0.00),携带GG基因型罹患结肠癌的风险明显增加5.12倍,且男性、吸烟结肠癌患者携带AG及GG基因型明显增加;2)CTLA-4-1661A/G:以AA基因型为对照,AG+GG基因型携带者的患病风险显著增高,为对照组的2.50倍(P=0.001),多态性与结肠癌患者的性别、年龄、肿瘤分化程度及TNM分期无相关性。结论:CTAL-4+49A/G及-1661A/G基因多态性与结肠癌的遗传易感性相关,性别、吸烟与否也是影响因素。

Objective： To analyze the relationship between extron 49 site and promoter 1661 in cytotoxic T lymphocyte antigen-4 （CTLA-4） gene potymorphism in Qingdao area and susceptibility to colorectal cancer. Methods： Polymerase chain restriction fragment length polymorphism and di- rect sequencing were performed to analyze the genotype of the A/G polymorphism in 49 site and 1661 site region. Results： 1）CTLA-4＋49A/G：The frequency of AG and GG genotype in 49 site were higher in the colorectal cancer group compared to the control group （P=0.00）. Individuals with the GG genotype rose to 5.12 fold risk for colorectal cancer, and men or with smoking in patients with colorectal cancer carried more AG and GG genotype. 2）CTLA-4-1661A/G：The frequency of AG＋GG genotype in 1661site was higher in the colorectal cancer group compared to the control group （P=0.001）,individuals with the AG＋GG genotype rose to 2.50 fold risk for colorectal cancer. Moreover,men or with smoking in patients with colorectal cancer carried more AG＋GG genotype. Conclusion： There is a relationship between CTLA-4＋49 A/G and 1661 A/G polymorphism and susceptibility to colorectal cancer.