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亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性
引用本文:金夏祥,朱忠政,王爱忠,贾杭若.亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性[J].世界华人消化杂志,2007,15(25):2754-2757.
作者姓名:金夏祥  朱忠政  王爱忠  贾杭若
作者单位:中国人民解放军第一一三医院病理科,浙江省宁波市,315040
基金项目:国家自然科学基金 , 江苏省南京军区医学科学技术研究计划
摘    要:目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态与结直肠癌(CRC)遗传易感性的关系.方法:采用TaqMan方法检测CRC 449例与对照672例的MTHFR C677T的基因型分布及差异.以非条件Logistic回归法计算表示相对危险度的比值比(OR)及其95%可信区间(CI).OR值均经性别、年龄、吸烟、饮酒、体质量指数和一级亲属CRC家族史等因素校正.结果:CRC组677T等位基因频率显著低于对照组,其为CRC发生的保护因素(OR:0.70,95%CI:0.58-0.83,P<0.01).与CC纯合子相比,CT杂合子的CRC风险显著降低至0.73倍(95%CI:0.56-0.95,P<0.05),而TT纯合子的CRC风险进一步降至0.47倍(95%CI:0.33-0.68,P<0.01).在非饮酒人群中,C677T的CRC风险保护效应略有增强;而在饮酒人群中,CT和TT基因型携带者的CRC发病风险虽仍低于CC基因型携带者,但差异无统计学意义.在CRC人群中,荷大肿瘤(最大直径>4cm)者携带TT基因型的比例高于荷小肿瘤者(16.3% vs 8.3%,P<0.05);荷黏液腺癌者携带TT基因型的比例高于荷乳头状腺癌及管状腺癌者(22.2% vs 17.1%,10.3%,P=0.084).结论:MTHFR C677T降低CRC发病风险,饮酒可能削弱该多态的CRC风险保护效应.TT基因型可能与CRC肿瘤进展有关.

关 键 词:结直肠肿瘤  亚甲基四氢叶酸还原酶  基因多态  遗传易感性
收稿时间:2007-07-10
修稿时间:2007-08-24

Association of methylenetetrahydrofolate reductase C677T polymorphism with genetic susceptibility to colorectal cancer
Xia-Xiang Jin,Zhong-Zheng Zhu,Ai-Zhong Wang,Hang-Ruo Jia.Association of methylenetetrahydrofolate reductase C677T polymorphism with genetic susceptibility to colorectal cancer[J].World Chinese Journal of Digestology,2007,15(25):2754-2757.
Authors:Xia-Xiang Jin  Zhong-Zheng Zhu  Ai-Zhong Wang  Hang-Ruo Jia
Abstract:AIM:To investigate the possible association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and genetic susceptibility to colorectal cancer (CRC). METHODS:The MTHFR C677T genotypes were determined by TaqMan assays in 449 cases of CRC and 672 controls.Odds ratios (ORs) for CRC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks.Potential CRC risk factors,including sex,age,cigarette smok- ing,alcohol drinking,body mass index and first- degree family history of CRC,were included in the logistic regression models as covariates in the multivariate analyses of genotype and CRC risk. RESULTS:The frequency of the T allele in the MTHFR C677T polymorphism was 0.360 in CRC and 0.444 in the controls.The T allele showed a significantly decreased risk for CRC (OR=0.70, 95% CI=0.58-0.83,P<0.01) when compared to the C allele.Compared to CC homozygotes,CT heterozygotes had a 0.73-fold decreased risk (95% CI=0.56-0.95,P<0.05),whereas TT homozy- gotes had a 0.47-fold decreased risk (95% CI=0.33 -0.68,P<0.01) of CRC.The inverse association of the C677T polymorphism with CRC risk was slightly stronger among non-drinkers (CT,OR =0.72,95% CI=0.53-0.98;TT,OR=0.40,95% CI=0.26-0.62).Among drinkers,however,no significant association of the MTHFR genotypes with CRC risk was observed,with an OR of 0.83 (95% CI=0.47-1.44) for heterozygotes and 0.75 (95% CI=0.37-1.55) for TT homozygotes when compared with CC homozygotes.No correlation was found between MTHFR C677T genotypes and tumor number,location,morphological pat- terns,histologic grade,presence of lymph node metastases,Dukes stage,or age at diagnosis.The TT genotype was more frequently found in pa- tients with a larger size tumor (>4 cm) than with a smaller size tumor (16.3% vs 8.3%,P<0.05), and was more frequently found in patients with mucinous adenocarcinoma than with tubular ad- enocarcinoma (22.2% vs 17.1%,10.3%,P=0.084). CONCLUSION:The MTHFR C677T polymor- phism is associated with a decreased risk of CRC,and alcohol consumption may negate some of the protective effect.The TT genotype may influence CRC progression.
Keywords:Colorectal cancer  Methylenetetrahydrofolate reductase  Genetic polymorphism  Genetic susceptibility
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