Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma

作者：Keitaro Matsuo, Ritsuro Suzuki, Nobuyuki Hamajima, Michinori Ogura, Yoshitoyo Kagami, Hirofumi Taji, Eisei Kondo, Satoko Maeda, Shoji Asakura, Sadayuki Kaba, Shigeo Nakamura, Masao Seto, Yasuo Morishima, Kazuo Tajima · 发表于：Blood · 年份：2001 · DOI：10.1182/blood.v97.10.3205 · 被引用次数：204 · 研究领域：Folate and B Vitamins Research、Epigenetics and DNA Methylation、RNA modifications and cancer

Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG typ...