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亚甲基四氢叶酸还原酶基因多态和叶酸摄取与乳腺癌的发病风险
引用本文:高长明,Kazuo Ta-jima,唐金海,曹海霞,丁建华,吴建中,王洁,刘燕婷,李苏平,苏平,Keitaro Matsuo,Toshim Takezaki. 亚甲基四氢叶酸还原酶基因多态和叶酸摄取与乳腺癌的发病风险[J]. 中华预防医学杂志, 2009, 43(7). DOI: 10.3760/cma.j.issn.0253-9624.2009.07.010
作者姓名:高长明  Kazuo Ta-jima  唐金海  曹海霞  丁建华  吴建中  王洁  刘燕婷  李苏平  苏平  Keitaro Matsuo  Toshim Takezaki
作者单位:1. 江苏省肿瘤防治研究所流行病审,南京,210009
2. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Japan
3. Department of Internatianal Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
基金项目:日本文部科技运动省国际科学研究癌症特别研究项目,江苏省科技厅社会发展重大项目 
摘    要:目的 研究亚甲基四氖叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)基因C677T、A1298C多态、饮食叶酸摄取与女性乳腺癌发病风险的关系.方法 采用病例-对照研究,收集江苏省乳腺癌患者669例,选取682名健康人作为埘照,用包括83个饮食项目的 定量问卷表调查研究对象的饮食状况.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测624例患者和624名对照者的MTHFR C677T和A1298C基因型,用非条件logistic回归进行分析,计算比值比(OR).结果 病例组的MTHFR C677T C/C,C/T和T/T基因型分别为32.37%(202/624)、48.88%(305/624)和18.75%(117/624),对照组分别为37.66%(235/624)、48.24%(301/624)和14.10%(88/624),两组的基因型分布差异有统计学意义(X2=6.616,P=0.037).T/T基因型者的乳腺癌发病风险显著升高[调整OR值为1.62(95%CI值:1.14~2.30)].病例组的MTHFRA1298C A/A、A/C和C/C基因型分别为71.47%(446/624)、27.08%(169/624)和1.44%(9/624),对照组分别为68.11%(425/624)、30.13%(188/624)和1.76%(11/624),两组间的基因型分布差异无统计学意义(X2=1.716,P=0.424).病例组的饮食叶酸摄取量[(263.00±137.38)μg/d]显著低于对照组[(285.12±149.61)μd](t=-2.830,P=0.005).与最低三分位组(≤199.08μg/d)相比,叶酸最高摄取量组(≥315.11μg/d)的OR值为0.70(95%CI值:0.53~0.92).在MTHFR A1298CA/A基因型者中,叶酸中间摄取量组(199.09~315.10μg/d)与最高摄取量组的OR值分别为0.89(95%C/值:0.62~1.27)、1.69(95%C/值:1.20~2.36),其线性趋势检验X2=11.372,P=0.001.结论 本研究结果 显示MTHFR遗传多态、饮食叶酸摄取与乳腺癌的发病风险相关.

关 键 词:乳腺肿瘤  亚甲基四氢叶酸还原酶  多态现象,遗传  叶酸

MTHFR polymorphisms,dietary folate intake and risks to breast cancer
CAO Chang-ming,Kazuo Ta-jima,TANG Jin-hai,CAO Hai-xia,DING Jian-hua,WU Jian-zhong,WANG Jie,LIU Yan-ting,LI Su-ping,SU Ping,Keitaro Matsuo,Toshim Takezaki. MTHFR polymorphisms,dietary folate intake and risks to breast cancer[J]. Chinese Journal of Preventive Medicine, 2009, 43(7). DOI: 10.3760/cma.j.issn.0253-9624.2009.07.010
Authors:CAO Chang-ming  Kazuo Ta-jima  TANG Jin-hai  CAO Hai-xia  DING Jian-hua  WU Jian-zhong  WANG Jie  LIU Yan-ting  LI Su-ping  SU Ping  Keitaro Matsuo  Toshim Takezaki
Abstract:Objective To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk. Methods A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and AI298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model. Results The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32. 37% (202/624), 48. 88% (3051624) and 18. 75% (117/624) in cases and 37. 66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls,respectively. The difference in distribution was significant (X2=6. 616, P=0. 037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2. 30). The frequencies of MTHFR A1298C A/A,A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68. 11% (425/624) ,30. 13% (188/624) and 1.76% (11/624) in controls, with no significant differences found (X2=1.716, P=0. 424). Folate intake of cases [(263.00±137. 38)μg/d]was significantly lower than that of controls [(285. 12±149. 61)μg/d](t=-2. 830,P=0. 005). Compared with the lowest tertile (≤199. 08μg/d) of folate intake,the adjusted OR for breast cancer in the top tertile (≥315.μg/d) was 0. 70 (95% CI:0. 53 -0. 92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0. 89 (95% CI: 0. 62 -1.27)and 1.69 (95% CI: 1.20 -2. 36) for the second to the third tertite of folato intake compared with thehighest folate intake group (Xtrend2=11. 372, P=0. 001). Conclusion The findings of the present study suggest that MTHFR genetic polymorphisms, and dietary intake of folate may modify susceptibility to breast cancer.
Keywords:Breast neoplasms  Methylenetetrahydrofolate reductase  Polymorphisms,genetic  Folic acid
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