Cytokine Gene Polymorphisms in Turkish Patients with Childhood Acute Lymphoblastic Leukemia.

Abstract

Cytokines are chemical mediators between cells and they bind on their own specific receptors on the target cells. Cytokine gene polymorphism may be implicated in the pathogenesis of infections autoimmun disease and malignancies via their effect on cytokine production and regulation. Leukemic cells proliferate under the influence of cytokines. It is known that acute lymphoblastic leukemia (ALL) which is sensitive to some cytokine gene is one of the hematological malignances derived from lymphoid tissue.Our aim is to determined frequencies of selected cytokines (TNF-α, TGF-β, IL-10, IL-6, IFN-γ) in childhood ALL patients and unrelated healthy control groups. We also investigated weather these polymorphism might contribute to the pathogenesis of ALL. Method: Genotyping was performed by polymerase chain reaction with sequence specific primers (PCR-SSP) using “ One lamda” kit in 44 ALL patients and 50 unrelated healthy individuals. Allelic frequencies were determined 24 polymorphism located within 16 cytokine genes. Genotype frequencies between ALL patients and controls were compared using Chi-Square Yates, Fisher's Exact Tests and Stepwise Logistic Regression Analysis (SLRA).Results: The frequency of TGF-β(TT/GG) allel (29,5% versus 8%, respectively;in chi-square p=0,007,odds ratio=4,82, 95% confidence interval (CI) 1,49–16,16; in SLRA p=0,002, OR=15,26,95% CI 2,77–84,05), TGF-β(TC/GG) allel (36,4% versus 10%, respectively; in chi-square p=0,002,odds ratio=5,14, 95% CI 1,69–15,59; in SLRA p=0,005,OR=10,21, 95% CI 2,02–51,61), IL-6(GC) allel (38,6% versus 8%, respectively; in chi-square p<0,001; odds ratio 7,24; 95% CI 2,20–23,76; in SLRA p=0,02,OR=6,37, 95% CI 1,22–33,15), IL-10(GCC/ATA) allel (36,4% versus 8%, respectively; in chi-square p=0,001, odds ratio 6,57, 95% CI 1,99–21,64; in SLRA p=0,01,OR=8,04, 95% CI 1,40–46,04), IFN-γ(TA) allel (54,5% versus 10%, respectively; in chi-square p<0,001, odds ratio 10,8, 95% CI 3,60–32,40; in SLRA p<0,001,OR=29,43, 95% CI 5,47–158,35) frequencies were found higher in patients with ALL compared to the control group. On the other hand IFN-γ(TT) allel (20% versus 48%, respectively; p=0,005; odds ratio 0,27; 95% CI 0,11–0,70), IFN-γ(AT)(0% versus 22%, respectively; p=0,001; odds ratio 1,28; 95%CI 1,10–1,48; fisher's exact=0,001) and IL-6(CA)(0% versus 22%, respectively; in chi-square p<0,001; odds ratio 1,28; 95% CI 1,10–1,28; fisher's exact=0,001) allel frequencies were found higher in the control group compared to the patients with ALL.TNF-α(GG) allel frequency was higher both in patients with ALL and in the control group (72% versus 85%). As a conclusion higher frequency in TGF-b(TT/GG),TGF-b(TC/GG),IL-6(GC), IL-10(GCC/ATA) and IFN-g(TA) allels may predispose to ALL.On the other hand IFN-g(TT), IFN-g(AT) and IL-6(CA) allels might be the preventive factor for ALL The present study is rather significant that it is the study which assessed the relation of the cytokines in patients with ALL compared to the control group taken from the genetic pool of The Turkish population but larger groups of studies must be done in future.