Department of Molecular and Genetic Toxicology, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Leuk Lymphoma. 2011 Oct;52(10):1949-60. doi: 10.3109/10428194.2011.589545. Epub 2011 Jun 24.
Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA methylation and nucleotide synthesis. Accumulated evidence has demonstrated that C677T and A1298C polymorphisms of the MTHFR gene are associated with acute lymphoblastic leukemia (ALL) risk, but the results have been inconclusive. To determine a more precise estimation, we performed a meta-analysis of 28 studies with 4240 cases and 9289 controls. We found that the 677TT genotype showed a reduced risk of ALL compared with the 677CC genotype in the overall population (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.92). The reduced risk was pronounced only among the Caucasian population (OR 0.68, 95% CI 0.51-0.90), not the Asian (OR 0.89, 95% CI 0.75-1.05). For the MTHFR A1298C polymorphism, no significant association with ALL susceptibility was observed in the pooled analyses. However, significantly increased ALL risk was found in childhood in the comparison of 1298CA versus AA genotype. This study provides evidence that MTHFR polymorphisms may play an important role in the development of ALL.
亚甲基四氢叶酸还原酶（MTHFR）参与 DNA 甲基化和核苷酸合成。大量证据表明，MTHFR 基因的 C677T 和 A1298C 多态性与急性淋巴细胞白血病（ALL）风险相关，但结果尚无定论。为了更准确地评估，我们对 28 项研究进行了荟萃分析，共纳入 4240 例病例和 9289 例对照。结果发现，677TT 基因型与 677CC 基因型相比，总体人群 ALL 的发病风险降低（比值比[OR] 0.76，95%置信区间[CI] 0.61-0.92）。这种降低的风险仅在白种人群中显著（OR 0.68，95%CI 0.51-0.90），而在亚洲人群中不显著（OR 0.89，95%CI 0.75-1.05）。对于 MTHFR A1298C 多态性，荟萃分析未发现其与 ALL 易感性相关。然而，在儿童 ALL 病例与对照的比较中，发现 1298CA 与 AA 基因型相比，ALL 发病风险显著增加。本研究提供了证据表明，MTHFR 多态性可能在 ALL 的发病机制中起重要作用。
