Polymorphisms in folate-related genes: impact on risk of adult acute lymphoblastic leukemia rather than pediatric in Han Chinese

Abstract

Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. An aberrant folate metabolism caused by a genetic polymorphism may lead to genomic instability and affect the susceptibility to malignancies including acute lymphoblastic leukemia (ALL). This study was designed to explore the correlation between the polymorphisms in folate-related genes and the risk of ALL in Han Chinese. The DNA was isolated from 231 patients with pediatric ALL, 130 patients with adult ALL, and 367 healthy subjects (as controls). Polymorphisms were examined for RFC1 80G > A, DHFR 19 bp del/ins and 317A > G, SHMT1 1420C > T, MTHFR 677C > T and 1298A > C, MTR 2756A > G, MTRR 66A > G, TYMS 3R/2R, MTHFD1 1958G > A, and ABCG2 421G > T using real-time polymerase chain reaction (PCR) or PCR–restriction fragment length polymorphism (RFLP). The risk of adult ALL was increased by the RFC1 80AA variant (odds ratio [OR] = 2.09; 95% confidence interval [CI] 1.19–3.67) and MTRR 66GG variant (OR = 2.15; 95% CI 1.06–4.39) but reduced by the MTHFR 677TT variant (OR = 0.47; 95% CI 0.25–0.88), ABCG2 421GT variant (OR = 0.62; 95% CI 0.41–0.96), and ABCG2 421GT + TT variant (OR = 0.60; 95% CI 0.40–0.90). The increase in risk of adult ALL with the RFC1 80AA associated with the MTRR 66GG variant was even more significant (OR = 8.92; 95% CI 1.97–40.42). Furthermore, the MTHFR 677TT associated with the ABCG2 421GT + TT variant more significantly reduced the risk of adult ALL (OR = 0.32; 95% CI 0.12–0.85). However, all gene polymorphisms tested in this study failed to affect the pediatric ALL risk. Our study clearly demonstrates that polymorphisms in folate-related genes only modulate the susceptibility to adult ALL, but not to pediatric ALL, in Han Chinese.