Cai D W, Liu X F, Bu R G, Chen X N, Ning L, Cheng Y, Wu B
Department of Urology, Shengjing Hospital of China Medical University, Shenyang City, Liaoning Province, China.
J Int Med Res. 2009 Nov-Dec;37(6):1882-9. doi: 10.1177/147323000903700625.
Epidemiological studies have shown that folate deficiency increases the risk of cancer by affecting DNA repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. In this study, it was hypothesized that MTHFR (C677T and A1298C) polymorphisms would be associated with bladder cancer and also with hypermethylation of the promoter of the Ras association domain family 1A (RASSF1A) gene. This hospital-based, case-control study of 312 bladder cancer patients and 325 cancer-free controls found that individuals carrying the MTHFR 677TT genotype had a 2.00-fold increased risk of bladder cancer compared with those carrying the 677CC genotype. None of the MTHFR A1298C polymorphisms alone were associated with bladder cancer, but the combined haplotype 677TT/1298AA was associated with a 2.27-fold increased risk compared with haplotype 677CC/1298AA. There was no association between MTHFR gene variants and methylation status of the RASSF1A gene in the 45 bladder cancer patients in whom this was studied. It is concluded that the MTHFR 677TT genotype and the TTAA haplotype may increase the risk of bladder cancer.
流行病学研究表明，叶酸缺乏会通过影响DNA修复和甲基化增加患癌风险。亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢中的关键酶。在本研究中，研究者推测MTHFR（C677T和A1298C）基因多态性可能与膀胱癌相关，也与Ras关联结构域家族1A（RASSF1A）基因启动子的高甲基化有关。这项基于医院的病例对照研究纳入了312例膀胱癌患者和325例无癌对照，结果发现，与携带677CC基因型的个体相比，携带MTHFR 677TT基因型的个体患膀胱癌的风险增加了2.00倍。单独的MTHFR A1298C基因多态性均与膀胱癌无关，但与单倍型677CC/1298AA相比，联合单倍型677TT/1298AA使风险增加了2.27倍。在对45例膀胱癌患者进行研究时，未发现MTHFR基因变异与RASSF1A基因的甲基化状态之间存在关联。研究得出结论，MTHFR 677TT基因型和TTAA单倍型可能会增加患膀胱癌的风险。
