Lv Long, Wang Ping, Sun Beicheng, Chen Gong
Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu Province, China.
Tumour Biol. 2014 Jan;35(1):227-37. doi: 10.1007/s13277-013-1028-0. Epub 2013 Jul 30.
Increasing epidemiological studies have revealed the important role of methylenetetrahydrofolate reductase (MTHFR) in carcinogenesis. The association of MTHFR A1298C and MTHFR C677T polymorphisms with the risk for gastric cancer remains obscure due to inconsistent findings in independent studies among diverse ethnicities. A meta-analysis based on all available publications on this genetic association was performed. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the effect of MTHFR variants on gastric carcinogenesis. Totally, 25 eligible case-control studies were included into the meta-analysis according to the inclusion criteria. The MTHFR C677T polymorphism was demonstrated to significantly increase the susceptibility to gastric cancer (OR(T vs. C) = 1.21, 95% CI 1.10-1.34; OR(TT vs. CC )= 1.47, 95% CI 1.22-1.76; OR(TC vs. CC )= 1.20, 95% CI 1.03-1.40; OR(TT + TC vs. CC) = 1.27, 95% CI 1.10-1.47; OR(TT vs. CC + TC )= 1.29, 95% CI 1.15-1.46), whereas no significant correlation was observed when assessing the MTHFR A1298C polymorphism (OR(C vs. A )= 1.00, 95% CI 0.90-1.10; OR(CC vs. AA) = 0.99, 95% CI 0.75-1.31; OR(CA vs. AA )= 1.01, 95% CI 0.89-1.14; OR(CC + CA vs. AA) = 1.00, 95% CI 0.89-1.13; OR(CC vs. AA + CA) = 0.97, 95% CI 0.74-1.27). Subgroup analyses by ethnicity and source of controls further confirmed the findings in overall analysis. The meta-analysis suggests that the polymorphism of MTHFR C677T but not MTHFR A1298C confers a risk effect on the development of gastric cancer among Asians and Caucasians, which provides a new insight into the gastric cancer pathogenesis.
越来越多的流行病学研究揭示了亚甲基四氢叶酸还原酶（MTHFR）在致癌过程中的重要作用。由于不同种族的独立研究结果不一致，MTHFR A1298C和MTHFR C677T基因多态性与胃癌风险之间的关联仍不明确。我们基于所有关于这种基因关联的可用出版物进行了一项荟萃分析。计算了合并比值比（OR）及其95%置信区间（95%CI），以评估MTHFR变异对胃癌发生的影响。根据纳入标准，共有25项符合条件的病例对照研究被纳入荟萃分析。结果表明，MTHFR C677T基因多态性显著增加了患胃癌的易感性（OR（T vs. C）=1.21，95%CI 1.10 - 1.34；OR（TT vs. CC）=1.47，95%CI 1.22 - 1.76；OR（TC vs. CC）=1.20，95%CI 1.03 - 1.40；OR（TT + TC vs. CC）=1.27，95%CI 1.10 - 1.47；OR（TT vs. CC + TC）=1.29，95%CI 1.15 - 1.46），而在评估MTHFR A1298C基因多态性时未观察到显著相关性（OR（C vs. A）=1.00，95%CI 0.90 - 1.10；OR（CC vs. AA）=0.99，95%CI 0.75 - 1.31；OR（CA vs. AA）=1.01，95%CI 0.89 - 1.14；OR（CC + CA vs. AA）=1.00，95%CI 0.89 - 1.13；OR（CC vs. AA + CA）=0.97，95%CI 0.74 - 1.27）。按种族和对照来源进行的亚组分析进一步证实了总体分析的结果。荟萃分析表明，MTHFR C677T而非MTHFR A1298C的基因多态性在亚洲人和高加索人中对胃癌的发生具有风险效应，这为胃癌发病机制提供了新的见解。
