engleski

Influence of IL-10 promoter SNPs on IL-10 mRNA expression in sporadic colorectal cancer

The influence of an individual's genetic background and identification of single nucleotide polymorphisms (SNPs) that contribute to cancer susceptibility is of great imortance in cancer prevention and treatment. Cytokines are important mediators of cancer development and progression due to their role in regulation of the immune response and cell growth. Various studies report that polymorphisms in cytokine genes may result in increased susceptibility to and/or poorer prognosis in certain cancer patients. Limited studies have suggested relationship between cytokine gene SNPs and their production. However, results of in vitro expression analysis are not always in accordance to the in vivo mRNA expression in tissues due to different experimental settings, inducers of mRNA expression and cell types analyzed.In this study we have examined the influence of IL-10 promoter SNPs -1082A/G, -819 T/C and -592 A/C on IL-10 mRNA expression in sporadic colorectal tumors. These SNPs were described as risk factors for development and/or progression in various types of cancer, however their importance in sporadic colorectal cancer has not been evaluated. Methods: DNAs and RNAs were extracted from 60 colorectal tumor tissue samples. Real-time PCR-SNP analysis of IL10 -1082A/G was performed using a TaqMan SNP genotyping assay C1747360_10. IL10 -819T/C and -592A/C SNPs were analysed by PCR-RFLP analysis with MaeIII (-819T/C) or RsaI (-592A/C) and submerged gel electrophoresis on Spreadex EL gels. Real-time RT-PCR analysis for IL-10 gene and house keeping gene RPLP0 was performed using TaqMan assay reagents, Hs00174086_m1 (IL-10) and Hs99999902_m1 (RPLP0).A statistically significant correlation between IL-10 mRNA expression and IL-10 SNPs was observed. IL-10 genotypes -1082 AA (p=0.022), -819 TT (p=0.013) and -592 AA (p=0.02) were associated with lower IL-10 mRNA expression. IL-10 promoter SNPs are associated with cancer susceptibility and prognosis in various studies. Since most SNP genotyping studies are not accompanied with mRNA expression analysis our study is a contribution to a rising pool of information concerning the influence of IL-10 promoter SNPs on the actual mRNA expression in tumors.

Interleukin-10; sporadic colon cancer; SNP; MRNA expression

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