Pro-(IL-18) and Anti-(IL-10) Inflammatory Promoter Genetic Variants (Intrinsic Factors) with Tobacco Exposure (Extrinsic Factors) May Influence Susceptibility and Severity of Prostate Carcinoma: A Prospective Study

Abstract

<b>Background:</b> It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variantsat -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk withvarious modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokineexpressed on various cells including prostate gland elements, and is a key mediator of immune responses withanti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancywhich causes immune escape. Materials and <br/><b>Methods</b>: The present study was conducted with 540 subjects,comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP andconfirmed by real time PCR probe-based methods. <br/><b>Results</b>: The findings indicated that the mutant heterozygousand homozygous genotype CC and GC+CC showed significant negative associations (p=0.01, OR=0.21; 95% CI:0.08-0.51 and p=0.011, OR=0.43; 95% CI: 0.22-0.81, respectively) thus, less chance to be diagnosed as canceragainst GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locusof IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so thatpatients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Ourresults also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significantassociation with susceptibility to cancer of the prostate, may gave profound effects on severity of the disease, as-819 TC (OR=4.60; 95%CI 1.35-15.73), and -592 AC (OR=5.04; 95%CI 1.08-25.43) of IL-10 in tobacco chewersand combined users (both chewers and smokers) respectively, are associated with diagnosis in more advancedstage than with other variants. <br/><b>Conclusions</b>: We conclude that promoter genetic variants of IL-18 and IL-10 withvarious modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.