Cytokine genetic polymorphisms and prostate cancer aggressiveness

Abstract

Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.

IL-10 polymorphisms and prostate cancer risk: a meta-analysis

“…31 For example, a previous report found that the association of IL-10 SNPs with PCa aggressiveness in CaucasianAmerican individuals and cytokine gene-SNP interactions might have a role in this process. 32 Many tumors induce various productions of cytokines, including IL-6, IL-8, IL-10 and tumor necrosis factor, to promote their own growth and limit immune responses. 33,34 Modulation and interactions of these cytokine productions may be pivotal for the control of inflammation and tumor progression.…”

Pro-inflammatory Genes as Biomarkers and Therapeutic Targets in Oral Squamous Cell Carcinoma

“…One important gene identified by this strategy was IL-8. High levels of IL-8 have been found in various human diseases and malignancies (17)(18)(19)(20)(21). IL-8 levels were found to be highly expressed in saliva of OSCC patients (22).…”

HOX transcription factors and the prostate tumor microenvironment

“…A role for IL8 in angiogenesis and its potential as a therapeutic target in cancer was demonstrated using fully-humanized antibodies to this protein in a mouse model of melanoma [87] , and it was subsequently shown that IL8 increases expression of the key proangiogenic ligand VEGF in endothelial cells resulting in a self-reinforcing, autocrine loop through the VEGF receptor 2 (VEGFR2) expressed on the surface of these cells [88] . Correspondingly, polymorphisms in the IL8 gene were shown to be associated with more aggressive prostate cancer [89] . CXCL1 is also a proangiogenic cytokine and has a potential role in the development of tumor resistance to anti-VEGF based therapy [90] , and in gastric cancer has been shown to promote tumor growth through the VEGF pathway [91] .…”