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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Zabaleta J,Su LJ,Lin HY,Sierra RA,Hall MC,Sartor AO,Clark PE,Hu JJ,Ochoa AC

doi

10.1093/carcin/bgp124

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

1358-62

issue

8

eissn

0143-3334

issn

1460-2180

pii

bgp124

journal_volume

30

pub_type

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