| dc.description.abstract | Endemic Burkitt lymphoma (eBL) is the most common paediatric cancer in sub-Saharan Africa and occurs at a high incidence in western Kenya. The tumour has the highest proliferative rate of any other human cancer. Although EBV and malaria co-infections appear to be primary factors in the aetiology of eBL, host genetic contributions that renders some children permissive to this pathologic pathway remains to be elucidated. Cytokine signals have the potential to be deletious in the context of lymphoma development by acting as growth facts and promoting tumour cell survival. Over expression of IL-6 and IL-I0 is suspected to playa role in the pathogenesis of eBL. It has been shown that genetic variants within the IL-6 and IL-IO gene promoters correlate with elevated levels of these cytokines, but whether these SNPs confer risk to eBL development is unknown. Children genetically predisposed to produce elevated levels of these cytokines may be more susceptible to eBL development. This case-control study investigated the association between the IL-6 (174G/C) and IL-IO (-1082A1G, -819Crr and -592C/A) promoter polymorphisms and susceptibility to eBL and whether these polymorphisms influence EBV loads in children (n=205) from western Kenya. DNA samples from 117 eBL cases and 88 healthy agematched controls were used in the analysis. A real-time polymerase chain reaction (PCR) using TaqMan allelic discrimination assay was used for genotyping. The EBV loads were measured using quantitative real-time PCR. The distribution of IL-6 and IL-IO genotypes was compared using X2 test. Across group comparisons were evaluated using Kruskal-Wallis test, while the association between the polymorphisms/haplotypes and susceptibility to eBL was determined using logistic regression analyses. Results showed comparable frequencies for IL-6 and IL-I0 genotypes between the cases and controls. Logistic regression analysis demonstrated that the individual IL-6 -174G/C (p=0.080), IL-I0 -1082A1G (p=0.900), 819Crr (P=O.541)and -592C/A (P=O.541) genotypes and the -1082A1-S19C/-592C (ACC) [p=0.671], ATA [P=O.356] and GeC [p=0.708] haplotypes were not associated with susceptibilityto eBL or increased EBV load. Results from this study do not eliminate a role for IL-6 and IL-IO in eBL pathogenesis however these common polymorphisms do not predisposeto eBL development. The baseline information from this study necessitates future studiesto explore other genetic variants regulating immune mediators that could contribute to eBLcarcinogenesis. | en_US |
