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Background. Interleukin-10 (IL-10) mediates angiogenesis, a biological process involved the formation of microvasculature necessary for growth and metastasis of solid tumors. We hypothesize that variations within the regulatory or coding regions of the IL-10 gene may reduce mRNA/protein expression, induce angiogenesis, and ultimately increase susceptibility to prostate cancer and disease progression. Objectives. A nested case-control study design was used to determine the association between low expressing IL-10 variant alleles and prostate cancer risk. A case-case analysis was used to examine the relationship between variant IL-10 genotypes and prostate cancer progression. Methods. Germ-line DNA, isolated from whole-blood, was collected from prostate cancer cases (n = 622) and controls (n = 622), matched on age and α-tocopherol intervention group, among middle-aged Finnish men. Participants were genotyped for four variants (-853T/C, -626A/C, -1116C/T and 210C/T) within the IL-10 gene using Taqman polymerase chain reaction. Results. The prevalence of the homozygous variant low expressing IL-10 -853CC, -626CC, -1116GG, and 210TT alleles were 61.6%, 4.4%, 20.0%, and 29.1%, respectively. We observed a linear increase (P-trend = 0.02) in prostate cancer risk among men who were heterozygous (ORadjusted = 1.26; 95% CI = 0.99-1.62) and homozygous variant (ORadjusted = 1.82; 95% CI = 1.06-3.16) for the IL-10 -626C low expressing allele. However, the low expressing IL-10 -853 C/C genotype was associated with a decrease in the risk of developing prostate cancer (ORadjusted = 0.54; 95% CI = 0.31-0.92; p = 0.02) and aggressive tumor grade, but not advanced disease. Haplotype analysis is currently underway, to assess the relationship between multiple variant IL-10 alleles and prostate cancer risk. Conclusions. A single nucleotide polymorphism at positions -626 within the regulatory region of IL-10 may increase the risk of developing prostate cancer among our study participants; however, the -853 T/C SNP may counteract this increase in disease susceptibility. Subsequent observational studies are required to further elucidate the role of IL-10 in the angiogenesis pathway and prostate cancer risk.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]