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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

  • Dwivedi, Shailendra (Department of Biochemistry, All India Institute of Medical Sciences) ;
  • Singh, Sarvesh (Department of Pharmacology and Therapeutics, King George Medical University) ;
  • Goel, Apul (Department of Urology, King George Medical University) ;
  • Khattri, Sanjay (Department of Pharmacology and Therapeutics, King George Medical University) ;
  • Mandhani, Anil (Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences) ;
  • Sharma, Praveen (Department of Biochemistry, All India Institute of Medical Sciences) ;
  • Misra, Sanjeev (Department of Surgical Oncology, All India Institute of Medical Sciences) ;
  • Pant, Kamlesh Kumar (Department of Pharmacology and Therapeutics, King George Medical University)
  • Published : 2015.04.29

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.

Keywords

Prostate carcinoma;tobacco smokers/chewers;combined users;IL-18;IL-10;genetic polymorphisms

Acknowledgement

Supported by : Indian Council of Medical Research

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