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Epidemiology/Lifestyle Factors: Molecular Epidemiology 1

Variability of serum IL-10 protein levels by IL-10 gene polymorphisms and individual characteristics and their association with colorectal adeanoma recurrence.

Cancer Prevention Fellowship Program, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Laboratory of Tumor Immunology & Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; Information Management Services, Inc., Rockville, MD; BioServe Biotechnologies, Ltd., Laurel, MD; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Bethesda, MD

Abstract

A189

Background Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays an important role in the regulation of inflammation in response to the immune system by inhibiting the production of pro-inflammatory cytokines. IL-10 may also play a role in the maintenance the cytokine network and progression of colorectal cancer. Serum levels of IL-10 have been shown to influence the pathology of many diseases, from autoimmune disorders to several types of cancer. IL-10 promoter single-nucleotide polymorphisms (SNPs) have been associated with inflammatory disease and a number of epithelial cancers, including colon cancer. Some studies have indicated that constitutive levels of IL-10 serum protein are genetically controlled by polymorphic variants at the cytokine gene promoter. Methods In this study, we examined the influence of three IL-10 promoter SNPs (-1082 A>G, -819 T>C, and -592 A>C), as well as IL-10 haplotypes, on constitutive IL-10 serum protein levels and on the association between serum levels and risk of recurrent colorectal adenomas. We also investigated whether diet, energy balance, and nonsteroidal anti-inflammatory drugs (NSAIDs) influenced individual IL-10 serum levels. The subjects were participants in the dietary control arm of the Polyp Prevention Trial who had available DNA for genotyping and a blood sample for the serum protein analysis. Genotyping for the IL-10 SNPs was performed by BioServe Biotechnologies Ltd. (Laurel, MD) and the IL-10 protein analysis was performed by Pierce Biotechology, Inc. (overall coefficient of variation was 11.6%). The distributions of IL-10 protein levels by individual characteristics were compared using Wilcoxon rank sum tests and odds ratios (ORs) and 95% confidence intervals (CIs) relating IL-10 SNPs, protein levels, and risk of adenoma recurrence were estimated using conditional logistic regression. Results We observed an increase in IL-10 serum protein levels with increasing age as well as with increasing BMI, however these differences were not statistically significant. We observed that individual's with the IL-10 -1082 G/G variant genotype had significantly reduced levels of IL-10 serum protein in the serum (mean IL-10 = 1.36 pg/mL), compared to individuals with the A/A genotype (mean IL-10 = 1.64 pg/mL) (p-value = 0.01). However, preliminary data does not indicate an association between the IL-10 serum protein levels and risk of colorectal adenoma recurrence (p-value = 0.74) or advanced adenoma recurrence (p-value = 0.30). We did not observe any statistically significant associations between IL-10 protein levels and adenoma recurrence.