Polymorphisms in one-carbon metabolism pathway genes, urinary arsenic profile, and urothelial carcinoma

Background: Gene polymorphisms in the one-carbon metabolism pathway could contribute to arsenic methylation capability through plasma folate and homocysteine metabolism, thereby increasing the susceptibility to urothelial carcinoma (UC) risk. Objectives: The goal of our study was to evaluate the roles of gene polymorphisms in the one-carbon metabolism pathway in the carcinogenesis of UC. Methods: A hospital-based case-controlled study was conducted. The urinary arsenic profile was examined using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Folate levels were measured using a competitive immunoassay kit. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism technique. Results: Patients with UC had higher urinary total arsenic, inorganic arsenic percentage (InAs%) and monomethylarsenic acid percentage (MMA%), and lower dimethylarsenic acid percentage (DMA%), plasma folate and homocysteine levels than controls. The correlations between folate and DMA%, and folate and homocysteine, were significant according to Pearson's correlation coefficients. Subjects carrying the 5,10-methylenetetrahydrofolate reductase (MTHFR) CT or TT genotype had a lower DMA% and lower folate levels than those carrying the CC genotype. Participants with the methionine synthase (MS) AA genotype had higher homocysteine levels than those with the AG or GG genotype. However, neither MTHFR nor MS gene polymorphisms were associated with UC risk. Conclusions: Environmental factors played a more important role in UC carcinogenesis than MTHFR or MS gene polymorphism.