Polymorphism G80A in the Reduced Folate Carrier Gene and its Relationship to Survival and Risk of Relapse in Acute Lymphoblastic Leukemia

Background: The reduced folate carrier (RFC1) is a major methotrexate transporter whose impaired function was recognized as a frequent mechanism of antifolate resistance. Recently, a G80A polymorphism has been described in the RFC1. This study evaluated the effect of the G80A polymorphism in the RFC1 gene on survival and risk of relapse of acute lymphoblastic leukemia. Methods and Results: Seventy patients with acute lymphoblastic leukemia were genotyped by polymerase chain reaction restriction fragment length polymorphism method. An association between the polymorphism and risk of relapse was found (P < 0.05). Patients with the G/A genotype have 3.97 (95% confidence interval, 1.12-14.06) and carriers of the A/A genotype have 7.84 (95% confidence interval, 1.66-37.10) higher chance of a relapse. Other variables such as age and leukocyte count were associated (P < 0.05) with the risk of relapse of disease. Individuals with G/A or A/A genotypes had poorer survival (log-rank test, P = < 0.05). Conclusions: These data suggest a role of the polymorphism G80A in the risk of relapse and the mortality risk in patients with acute lymphoblastic leukemia from the State of Guerrero, Mexico.