Polymorphism of 5,10-Methylenetetrahydrofolate Reductase Gene and Risk of Acute Lymphoblastic Leukemia in Korea

초록

The 5,10-methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has 2 variant, C677T and A1298C, that results in decreased MTHFR activity and lower plasma folate levels. MTHFR C677T variant is known to be associated with deceased risk of acute lymphoblastic leukemia (ALL) in Caucasian. In this study, we hypothesized that A1289C variant may also play a role in carcinogenesis of acute leukemia. The genotype distribution for C677T and A1289C alleles were compared between 133 Korean ALL patients (89 adults and 44 children) and 288 healthy age matched controls (254 adults and 34 children). Among 89 adults ALL patients, the MTHFR 677T genotype allele frequency was 0.36 compared with 0.39 among 254 control subjects. Frequencies of MTHFR 677CC, 677CT, and 677TT genotype were 36.0%, 56.2%, and 7.9% in the cases and 35.8%, 50.8%, and 13.4% in the controls respectively. For MTHFR 1298C, a mutant allele frequency was 0.22 in the cases and 0.26 in the controls. Frequencies of MTHFR 1298AA, 1298AC, and 1298CC genotype were 49.1%, 49.1%, and 1.8% in the cases and 77.4%, 20.7%, 1.9% in the controls respectively. Individuals with C677T mutation had decreased tendency to develop ALL in adults but statistically not significant (OR 0.577, CI 0.234-1.425; p=0.229) compared with the homologous normal. However, compared to MTHFR 1298AA and combined 677CC/1298AA types, MTHFR 1298AC (OR 3.278, 95% CI 19.555; p=0.0064) and 677CT/1298AC (OR 1.655, CI 1.245-2.201; p=0.0005) types were significantly increased in adult ALL compared with controls. We could not find any significant association between the MTHFR C677T and A1298C genotypes in childhood ALL. In summary, individuals with the 1298AC mutation may be associated with the risk of ALL in Korean adults.