National Key Clinical Specialty of Urology, Second Affiliated Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin, China.
PLoS One. 2013 Jul 19;8(7):e69366. doi: 10.1371/journal.pone.0069366. Print 2013.
Studies investigating the association between single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and cancer risk report conflicting results. To derive a more precise estimation of the relationship between MTHFD1 polymorphisms and cancer risk, the present meta-analysis was carried out.
METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search was conducted to determine all the eligible studies about MTHFD1 polymorphisms and cancer risk. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between the MTHFD1 polymorphisms and cancer risk. We investigated by meta-analysis the effects of 2 polymorphisms in MTHFD1: G1958A (17 studies, 12348 cases, 44132 controls) and G401A (20 studies, 8446 cases, 14020 controls). The overall results indicated no major influence of these 2 polymorphisms on cancer risk. For G1958A, a decreased cancer risk was found in acute lymphoblastic leukemia (ALL)/Asians (the dominant: OR = 0.74, 95% CI = 0.58-0.94, P = 0.01; allelic: OR = 0.80, 95% CI = 0.65-0.99, P = 0.04) and other cancers (recessive: OR = 0.80, 95% CI = 0.66-0.96, P = 0.02). For G401A, the data showed that MTHFD1 G401A polymorphism was associated with a decreased colon cancer risk under dominant model (OR = 0.89, 95% CI = 0.80-0.99, P = 0.04).
The results suggest that MTHFD1 G1958A polymorphism might be associated with a decreased risk of ALL and other cancers. Meanwhile, the MTHFD1 G401A might play a protective role in the development of colon cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.
研究单核苷酸多态性（SNP）与癌症风险之间的关系表明，亚甲基四氢叶酸脱氢酶 1（MTHFD1）存在冲突结果。为了更准确地评估 MTHFD1 多态性与癌症风险之间的关系，进行了本次荟萃分析。
方法/主要发现：全面检索了有关 MTHFD1 多态性与癌症风险的所有合格研究。使用合并优势比（OR）和 95％置信区间（CI）来评估 MTHFD1 多态性与癌症风险之间的关联强度。通过荟萃分析研究了 MTHFD1 中的 2 种多态性的影响：G1958A（17 项研究，12348 例病例，44132 例对照）和 G401A（20 项研究，8446 例病例，14020 例对照）。总体结果表明，这两种多态性对癌症风险没有重大影响。对于 G1958A，在急性淋巴细胞白血病（ALL）/亚洲人群（显性：OR = 0.74，95％CI = 0.58-0.94，P = 0.01；等位基因：OR = 0.80，95％CI = 0.65-0.99，P = 0.04）和其他癌症（隐性：OR = 0.80，95％CI = 0.66-0.96，P = 0.02）中发现癌症风险降低。对于 G401A，数据表明，MTHFD1 G401A 多态性与显性模型下结肠癌风险降低相关（OR = 0.89，95％CI = 0.80-0.99，P = 0.04）。
结果表明，MTHFD1 G1958A 多态性可能与 ALL 和其他癌症的风险降低有关。同时，MTHFD1 G401A 可能在结肠癌的发生中起保护作用。需要进行大规模和精心设计的病例对照研究来验证本荟萃分析中确定的风险。
