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Polymorphisms of MTHFD,plasma homocysteine levels, and risk of gastric cancer in ahigh-risk Chinese population

南京医科大学学报（自然科学版） 2007年第7期27卷 670-670页

作者： Wang, L. N Ke, Q Chen, W. S Wang, J. M Tan, Y. F Zhou, Y Hua, Z. L Ding, W. L Niu, J. Y Shen, J Zhang, Z. F Wang, X. R Xu, Y. H Shen, H. B Yi Xing Nanjing Med Univ Dept Epidemiol ＆ Biostat lnst Toxicol Nanjing 210029 Peoples R China Peoples Hosp Yangzhong Peoples R China. Univ Calif Los Angeles Sch Publ Hlth Dept Epidemiol Los Angeles CA 90024 USA.

Purpose:Accumulative evidence suggests that folate has a protective effect on gastric cancer. The methylenetetrahyd-rofolate dlehydrogenase(MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase(MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine(tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results:The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric canceradjusted odds ratio(OR), 2.05; 95% confidence interval(95% CI),1.34-3.13 for 1958AA; adjusted OR,1.43; 95% CI,1.14-1.80 for 401CC compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TT genotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls(P 13.6 mu mol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy(<= 8.0 pmol/L;adjusted OR,1.82; 95% CI,1.20-2.75). Conclusions:The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.

关键词：等离子体同型半胱氨酸胃癌高风险人群多态性 MTHFD 神经管缺陷白血病还原酶

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