Association of IL-27 rs153109 and rs17855750 Polymorphisms with Risk and Response to Therapy in Acute Lymphoblastic Leukemia

Abstract

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p < 0.001). Combined G variant genotypes (AG + GG and TG + GG) also conferred significantly greater risk of ALL. There was a significant correlation between the genotypes of both SNPs with event-free survival (EFS). Patients with GG genotypes of both SNPs and those of rs153109 AG and rs17855750 TG had a shorter EFS than patients with rs153109 AA and rs17855750 TT genotypes (p ≤ 0.035). Combined G variant genotypes for both SNPs showed poorer response to therapy in all patients (p < 0.027) as well as B-ALL (rs153109, p < 0.001) and T-ALL (rs153109, p = 0.048) patients. In multivariate analysis, rs153109 combined G variant genotype was associated with shorter EFS (relative risk = 9.7, p = 0.026). Among those who relapsed, 87.1% had the rs153109 AG genotype and 77.4% had the rs17855750 TG genotype (p < 0.01). Patients had higher IL-27 serum levels compared to controls, but this did not differ between genotypes. In conclusion, the association of IL-27 rs153109 and rs17855750 polymorphisms with risk of ALL development and their impact on EFS suggested an important role for this cytokine in biology and response to ALL therapy.

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