Association between interleuleukin-1β polymorphism (rs16944) and biomarkers levels in Iraqi patients with prostate cancer.

Abstract

Prostate cancer (PCa) is the second-leading cause of mortality in men and the most commonly diagnosed non-cutaneous male malignancy. Host genetic factors, and inflammation-induced cytokines, play a key role in prostate oncogenesis. Single Nucleotide Polymorphisms (SNP) in cytokine genes were suggested to increase the susceptibility for PCa development and progression. This study aimed to investigate the association between the SNP (rs16944) in the interleukin-1 β (IL-1β) gene and the serum levels of Prostate Specific Antigen (PSA) Prolactine (PRL), testosterone, and IL-1β in Iraqi PCa patients versus healthy controls. Taqman Real Time-PCR, was performed to investigate the IL-1β (rs16944) polymorphism in 100 Iraqi PCa patients and 50 age-matched healthy controls in a case-control study. Serum levels of PSA, PRL, and testosterone were determined by ELISA and FIA, and associated with the IL-1β serum level as well as with the SNP (rs 16944). The association between the clinico-pathological parameters and the genotype distribution of PCa patients was also studied. There level of IL-1β was significant increased in the serum of PCa patients compared to controls (P = 8.19 10-7). Serum levels for other biomarkers such as PSA, PRL and testosterone were also significantly elevated in patients compared to controls (P < 0.0001). No differences were seen for genotype and allele distribution between PCa patients and controls. Nevertheless, in the group of controls, we found that 36% carried the GG genotype against only 26% in the patients group.This suggests that this could be a protective genotype (OR 0.62, P = 0.254). In addition, we found that the GA genotype is slightly more frequent in patients as compared to controls (OR 1.22, P = 0.605). Interestingly, serum levels of IL-1β, PSA, PRL and testosterone were significantly higher in PCa patients carrying the GA genotype, and the GA and AA genotypes are strongly associated with the aggressive behavior of the disease such as advanced TNM, and high Gleason score. Our data suggest that both serum IL-1β level and IL-1β SNP (rs16944) may be considered as candidate biomarkers for PCa. Moreover, the GA, and AA genotypes carriers along with high sera levels of IL-1β, PSA and PRL, have an increased risk for PCa with aggressive behavior in Iraqi men.