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

BACKGROUND:

It has been hypothesized that IL-18 (pro-) and IL-10 (anti-) inflammatory genetic variants at -607 C/A-137G/C and -819C/T,-592C/A, respectively, may generate susceptibility and severity risk with various modes of tobacco exposure in prostate carcinoma (PCa) patients. IL-18 is a pro-inflammatory cytokine expressed on various cells including prostate gland elements, and is a key mediator of immune responses with anti-cancerous properties. IL-10 is an anti-inflammatory cytokine that is associated with tumour malignancy which causes immune escape.

MATERIALS AND METHODS:

The present study was conducted with 540 subjects, comprising 269 prostate carcinoma patients and 271 controls. Genotyping was performed by PCR-RFLP and confirmed by real time PCR probe-based methods.

RESULTS:

The findings indicated that the mutant heterozygous and 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 cancer against GG genotype of tobacco smoking patients. In addition, a heterozygous GC genotype at the same locus of IL-18 pro-inflammatory cytokine may aggravate the severity (OR=2.82; 95%CI 1.09-7.29 :p=001) so that patients are more likely to be diagnosed in advanced stage than with the GG wild homozygous genotype. Our results also illustrated that anti-inflammatory cytokine (IL-10) genetic variants, although showing no significant association 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 chewers and combined users (both chewers and smokers) respectively, are associated with diagnosis in more advanced stage than with other variants.

CONCLUSIONS:

We conclude that promoter genetic variants of IL-18 and IL-10 with various modes of tobacco exposure may affect not only susceptibility risk but also severity in prostate cancer.

• Authors: Shailendra Dwivedi, Sarvesh Singh, Apul Goel, Sanjay Khattri, Anil Mandhani, Praveen Sharma, Sanjeev Misra, Kamlesh Kumar Pant
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 16 Issue 8 Pg. 3173-81 ( 2015) ISSN: 2476-762X [Electronic] Thailand
• PMID: 25921117 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Interleukin-18
• Interleukin-10

Topics

• Adult
• Aged
• Aged, 80 and over
• Case-Control Studies
• Follow-Up Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin-10 (genetics)
• Interleukin-18 (genetics)
• Male
• Middle Aged
• Neoplasm Grading
• Polymerase Chain Reaction
• Polymorphism, Genetic (genetics)
• Polymorphism, Restriction Fragment Length
• Prognosis
• Promoter Regions, Genetic (genetics)
• Prospective Studies
• Prostate (metabolism)
• Prostatic Neoplasms (etiology, pathology)
• Tobacco Use (adverse effects)