Private Practice of Urology and Andrology, PO Box 19395-1849, Tehran, Iran.
Med Oncol. 2011 Dec;28 Suppl 1:S398-412. doi: 10.1007/s12032-010-9723-9. Epub 2010 Oct 29.
We performed a case-control study of 158 bladder transitional cell carcinoma (TCC) cases and 316 controls to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298G, and G1793A polymorphisms and bladder cancer susceptibility by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. The controls were frequency-matched to the cases by age (± 5 years), ethnicity, and smoking status. We also measured serum levels of total homocysteine (tHcy), folate, and vitamin B12. It was found that the 1298AC (odds ratio, OR = 3.74; 95% confidence interval, CI = 2.34-5.47; P = 0.001) and 1298CC (OR = 3.46, 95% CI = 2.37-5.52; P = 0.001) genotypes of MTHFR A1298C were significantly associated with increased risk of bladder TCC. The MTHFR C677T and G1793A polymorphisms were not associated with bladder TCC. After stratification for grade and stage, we observed that the 677TT (OR = 4.47, 95% CI = 2.74-6.72; P = 0.001) and MTHFR 1298CC (OR = 4.78, 95% CI = 2.82-6.89; P = 0.001) genotypes of MTHFR were associated with increased risk of muscle-invasive bladder TCC. We also found that the MTHFR 677CT+1298AA genotypes were associated with an approximately 70% reduction in risk of bladder cancer (OR = 0.31; 95% CI = 0.15-0.68) compared to the combined referent genotype. There were 8 haplotypes and 16 haplotype genotypes based on these three variants. When we used the haplotypes and assumed that the 677T, 1298C, and 1793G alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.88 (1.4-2.7) for any two risk alleles and 2.07 (1.6-2.8) for any three risk alleles. Serum tHcy levels were significantly higher in carriers of the 677T, 1298C, and 1793G alleles compared to noncarriers (all P < 0.01). There was no significant correlation between serum levels of tHcy and folate and bladder cancer risk. Further studies in larger samples size and different ethnicity are required to confirm our findings.
我们进行了病例对照研究，共纳入 158 例膀胱癌病例和 316 例对照，采用聚合酶链反应限制性片段长度多态性（PCR-RLFP）技术，分析亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298G 和 G1793A 多态性与膀胱癌易感性的关系。通过年龄（±5 岁）、种族和吸烟状况，将对照组与病例组进行频数匹配。我们还测量了总同型半胱氨酸（tHcy）、叶酸和维生素 B12 的血清水平。结果发现，MTHFR A1298C 的 1298AC（比值比，OR = 3.74；95%置信区间，CI = 2.34-5.47；P = 0.001）和 1298CC（OR = 3.46，95% CI = 2.37-5.52；P = 0.001）基因型与膀胱癌风险增加显著相关。MTHFR C677T 和 G1793A 多态性与膀胱癌无关。在按分级和分期分层后，我们观察到 MTHFR 677TT（OR = 4.47，95% CI = 2.74-6.72；P = 0.001）和 MTHFR 1298CC（OR = 4.78，95% CI = 2.82-6.89；P = 0.001）基因型与肌层浸润性膀胱癌风险增加显著相关。我们还发现，与联合参考基因型相比，MTHFR 677CT+1298AA 基因型与膀胱癌风险降低约 70%（OR = 0.31；95% CI = 0.15-0.68）相关。基于这三个变体，存在 8 个单倍型和 16 个单倍型基因型。当我们使用单倍型并假设 677T、1298C 和 1793G 等位基因为风险等位基时，随着风险等位基数量的增加，调整后的比值比增加：0-1 个变体的 1.00，任何两个风险等位基的 1.88（1.4-2.7）和任何三个风险等位基的 2.07（1.6-2.8）。与非携带者相比，携带 677T、1298C 和 1793G 等位基的个体血清 tHcy 水平显著升高（均 P < 0.01）。血清 tHcy 水平与叶酸和膀胱癌风险之间没有显著相关性。需要在更大的样本量和不同种族中进行进一步研究，以证实我们的发现。
