Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population
Methylenetetrahydrofolate reductase C677T polymorphism and predisposition towards esophageal squamous cell carcinoma in a German Caucasian and a northern Chinese population
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DOI：
10.1007/s00432-004-0585-4
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发表时间：
2004-07
影响因子：
3.6
通讯作者：
Jian-hui Zhang;R. Zotz;Yan Li;Rui Wang;S. Kiel;W. Schulz;D. Wen;Zhi-feng Chen;Liwei Zhang;Shijie Wang;H. Gabbert;M. Sarbia
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文献类型：
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作者：
Jian-hui Zhang;R. Zotz;Yan Li;Rui Wang;S. Kiel;W. Schulz;D. Wen;Zhi-feng Chen;Liwei Zhang;Shijie Wang;H. Gabbert;M. Sarbia
叶酸缺乏被认为是增加食管癌发病风险的重要因素。亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢的关键酶。MTHFR cDNA的核苷酸677处的单个C → T取代影响酶活性。本研究的目的是比较MTHFR C677 T多态性与食管鳞状细胞癌（ESCC）易感性的关系。检测430例食管鳞癌患者MTHFR C677 T基因型（241名德国白人和189名北方中国人）和397名无关的健康对照结果MTHFR C677 T基因型分布在德国白种人和中国北方人中有显著差异（C/C，41.8%，C/T，44.9%，T/T，13.3%）与北方中国对照组（C/C，17.7%，C/T，38.3%，T/T，44.0%）比较，差异有显著性（χ2= 52.19，P <0.001）。德国ESCC患者MTHFR C677 T基因型分布（C/C，39.0%，C/T，48.1%，T/T，12.9%）与健康对照组比较差异无统计学意义（χ2= 0.531，P =0.767）。ESCC患者C/C基因型频率（8.5%）显著低于健康对照组（17.7%）（χ2= 6.37，P =0.012）。与C/T和T/T基因型的组合相比，C/C基因型与ESCC的发展风险显著降低相关（调整OR=0.38，95%CI =0.16-0.88）。结论我们的研究结果表明，与德国高加索人相比，MTHFR 677 CC纯合子野生型在北方中国人群ESCC的发展中起着保护作用。
PurposeFolate deficiency is considered to increase the risk of developing esophageal cancer. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. A single C → T substitution at nucleotide 677 of the MTHFR cDNA influences enzyme activity. The purpose of this study is to compare the association of the MTHFR C677T polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC).MethodsUsing real-time PCR and melting curve analysis, the MTHFR C677T genotypes were determined in 430 patients with ESCC (241 German Caucasians and 189 northern Chinese) and 397 unrelated healthy controls (256 German Caucasians and 141 northern Chinese).ResultsA significant difference in MTHFR C677T genotype distribution was observed between German Caucasian controls (C/C, 41.8%, C/T, 44.9%, T/T, 13.3%) and northern Chinese controls (C/C, 17.7%, C/T, 38.3%, T/T, 44.0%) (χ2=52.19,P<0.001). The distribution of the MTHFR C677T genotypes among German ESCC patients (C/C, 39.0%, C/T, 48.1%, T/T, 12.9%) was not significantly different from that among healthy controls (χ2=0.531,P=0.767). In contrast, the frequency of the C/C genotype among Chinese ESCC patients (8.5%) was significantly lower than among Chinese healthy controls (17.7%) (χ2=6.37,P=0.012). The C/C genotype was correlated with a significantly reduced risk for the development of ESCC as compared to the combination of C/T and T/T genotypes (adjusted OR=0.38, 95% CI=0.16–0.88).ConclusionsOur results suggest that, in contrast to German Caucasians, the MTHFR 677CC homozygous wild-type plays a protective role in the development of ESCC in the northern Chinese population.