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  • 冯伟,陆乘俊,吴俊杰,李玉涛,倪宏宇,金力,卢大儒,王久存,李菊红.亚甲基四氢叶酸还原酶基因rs1801133位点多态性与肺癌发生风险的关联分析[J].第二军医大学学报,2019,40(7):769-775    [点击复制]
  • FENG Wei,LU Cheng-jun,WU Jun-jie,LI Yu-tao,NI Hong-yu,JIN Li,LU Da-ru,WANG Jiu-cun,LI Ju-hong.Association of methylenetetrahydrofolate reductase gene rs1801133 polymorphism with lung cancer risk[J].Acad J Sec Mil Med Univ,2019,40(7):769-775   [点击复制]
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亚甲基四氢叶酸还原酶基因rs1801133位点多态性与肺癌发生风险的关联分析
冯伟1,陆乘俊2,吴俊杰3,4*,李玉涛4,倪宏宇4,金力4,5,卢大儒4,5,王久存4,5,李菊红6*
0
(1. 海军军医大学(第二军医大学)基础医学院学员二大队4队, 上海 200433;
2. 泰州市中医院胸外科, 泰州 225309;
3. 海军军医大学(第二军医大学)长海医院呼吸与危重症医学科, 上海 200433;
4. 复旦大学现代人类学教育部重点实验室, 上海 200433;
5. 复旦大学泰州健康科学研究院, 泰州 225300;
6. 海军军医大学(第二军医大学)长海医院健康体检中心, 上海 200433
*通信作者)
摘要:
目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因rs1801133位点多态性与肺癌发生风险的相关性。方法 采用病例-对照研究设计,纳入上海市及江苏省泰州地区肺癌患者974例和健康对照1 005例作为研究对象,采集研究对象外周血液后提取全血基因组DNA进行MTHFR基因rs1801133位点基因分型,用非条件logistic回归分析评估该位点单核苷酸多态性与肺癌发生风险的相关性。结果 总人群中MTHFR基因rs1801133位点CT基因型与TT基因型个体肺癌的发生风险均低于CC基因型个体[比值比(OR)=0.801,95%置信区间(CI):0.651~0.985,P=0.035;OR=0.754,95%CI:0.582~0.975,P=0.032],但经年龄、性别、吸烟状况和恶性肿瘤家族史校正后差异无统计学意义(校正后OR=0.841,95%CI:0.677~1.045,P=0.118;OR=0.799,95%CI:0.609~1.047,P=0.104)。校正后分层分析结果显示,在显性模型中CT+TT基因型男性和恶性肿瘤家族史阳性者肺癌发生风险均较CC基因型对应人群降低(OR=0.764,95%CI:0.597~0.977,P=0.032;OR=0.600,95%CI:0.385~0.925,P=0.022),CT+TT基因型人群发生肺鳞状细胞癌的风险较CC基因型人群降低(OR=0.727,95%CI:0.542~0.976,P=0.033)。结论 MTHFR基因rs1801133位点C>T突变降低了男性和恶性肿瘤家族史阳性者肺癌的发生风险,尤其是鳞状细胞癌的患病风险。
关键词:  亚甲基四氢叶酸还原酶基因  rs1801133  单核苷酸多态性  肺肿瘤
DOI:10.16781/j.0258-879x.2019.07.0769
投稿时间:2018-11-22修订日期:2019-04-30
基金项目:国家自然科学基金(81372236),国家科技支撑计划重点项目(2011BAI09B00),海军军医大学(第二军医大学)本科生创新实践能力孵化基地(FH2017186).
Association of methylenetetrahydrofolate reductase gene rs1801133 polymorphism with lung cancer risk
FENG Wei1,LU Cheng-jun2,WU Jun-jie3,4*,LI Yu-tao4,NI Hong-yu4,JIN Li4,5,LU Da-ru4,5,WANG Jiu-cun4,5,LI Ju-hong6*
(1. The Second Student Team, College of Basic Medical Sciences, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Thoracic Surgery, TCM Hospital of Taizhou, Taizhou 225309, Jiangsu, China;
3. Department of Respiratory Medicine, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
4. Key Laboratory of Contemporary Anthropology of Ministry of Education, Fudan University, Shanghai 200433, China;
5. Taizhou Institute of Health Sciences, Fudan University, Taizhou 225300, Jiangsu, China;
6. Center of Physical Examination, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding authors)
Abstract:
Objective To explore the association between methylenetetrahydrofolate reductase (MTHFR) rs1801133 polymorphism and lung cancer risk. Methods This case-control study included 974 lung cancer patients and 1 005 healthy controls living in Shanghai and Taizhou, Jiangsu Province. After collecting the peripheral blood samples of the participants, the whole blood genomic DNA was extracted for MTHFR gene rs1801133 genotyping. The effect of rs1801133 on lung cancer susceptibility was analyzed through unconditional logistic regression analysis. Results Compared with CC genotype, MTHFR rs1801133 CT and TT genotypes significantly decreased lung cancer risk (odds ratio[OR]=0.801, 95% confidence interval[CI]:0.651-0.985, P=0.035; OR=0.754, 95% CI:0.582-0.975, P=0.032), but this association became insignificant after adjusting age, gender, smoking status, and family cancer history (OR=0.841, 95% CI:0.677-1.045, P=0.118; OR=0.799, 95% CI:0.609-1.047, P=0.104). However, in dominant model, CT+TT genotypes exhibited a significantly reduced lung cancer risk in males (OR=0.764, 95% CI:0.597-0.977, P=0.032) and those with a family cancer history (OR=0.600, 95% CI:0.385-0.925, P=0.022), and a significantly reduced risk for having squamous cell carcinoma (OR=0.727, 95% CI:0.542-0.976, P=0.033). Conclusion The MTHFR gene rs1801133 C>T mutation might reduce the risk of lung cancer in males and those with a family history of cancer, especially those with squamous cell carcinoma.
Key words:  methylenetetrahydrofolate reductase  rs1801133  single nucleotide polymorphism  lung neoplasms