IL2 polymorphisms have no impact on risk, but genetic variants in IFNG have a protective role in acute lymphoblastic leukemia and are associated with gender in Mexican children

Abstract

Aim Acute lymphoblastic leukemia (ALL) is the most common cancer in children (26%). ALL patients present a defective immune system with deregulation of cytokine production. A lower population of IL-2 and INF- γ producer cells Th1 and Tc1 are evident in ALL patients. These cytokines promote cellular immunity and its protein production may be altered by inherited polymorphisms. The aim of this study was to evaluate the role of IFNG(+874 A/T) and IL2(−330 G/T) SNPs in the expression of ALL in Mexican children and the gender influence in susceptibility to the disease. Methods ALL patients (N = 148) were genotyped for INFG and 110 for IL2; 376 healthy controls were included for comparison. All individuals are Mexican Mestizos, born in Mexico. The patients’ age ranged between 1 and 17 years; 59.4% were males and 40.6% females. DNA was obtained from peripheral blood samples using the Maxwell16 instrument. Allele discrimination of IFNG +874A/T(rs2430561) and IL2 −330 G/T(rs2069762) was performed using a Taqman real time PCR assay and an ABI 7500 Real-Time PCR equipment. Results A protective role of IFNG(+874A/T) SNP was shown for the expression of ALL. The frequency of the T allele (OR = 0.482; p = 0.00005) and TT genotype (OR = 0.052 p = 0.000006) were found decreased in the patients, while AA genotype was increased (OR = 1.86; CI 1.25–2.76; (p = 0.003). Upon sex-stratification, TT was protective in both, males (OR = 0.087; p = 0.003) and females (OR = 0.127; p = 0.02). IL2(−330G/T) SNP did not show any statistical deviation between cases and controls. Conclusions IL2(−330 G/T) was not associated with the development of childhood ALL. However, our results support the role of IFNG (+874 A/T) in surveillance against tumor cells in ALL in Mexican Mestizo children, IFNG +874 TT genotype has been associated with high cytokine production, since +874T matches with the transcription factor NF- κ B binding site that may enhance IFNG transcription. The cytokine has antitumor and anti-proliferative properties; and our data agree with other reports emphasizing the role of IFN- γ alleles in immune surveillance and its possible effect as an immunotherapeutic agent in certain forms of ALL. Moreover, recent data suggest the association of TT genotype on age at clinical onset in B-lineage ALL, in older children expressing the TT high producing IFN- γ genotype.