Functional genetic variability at promoters of pro-(IL-18) and anti-(IL-10) inflammatory affects their mRNA expression and survival in prostate carcinoma patients: Five year follow-up study.
BACKGROUND
Inflammation is an important hallmark of all cancers. The net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which, in turn, is determined by the genetic make-up. The present study investigates the role of variations in the promoter regions of IL-18 and IL-10 (anti-inflammatory) cytokines on mRNA expressions and survival in prostate cancer (PCa) patients.


METHODS
The study was conducted on 584 volunteer males (291 patients of PCa, between 40-80 years of age. Genetic variants were studied by using RFLP and confirmed by probe based method. Expressions of mRNA were evaluated by real-time PCR (Roche light cycler 480). Relative mRNA and fold change gene expressions were analyzed by ([1/2] (ΔCt) ) and (2(-ΔΔCt) ) methods, respectively, and 5 year follow-ups were evaluated by Log-rank (Mantel-Cox) test with Log-rank test for trends.


RESULTS
IL-18 mRNA expression was significantly elevated in GG genotypes (at -137) of PCa with relative mRNA expression of 13.95, that is, 8.48 folds higher (P < 0.05) than controls; and showed a significant median survival of 1243 days. The CC genotypes of IL-10 at both loci (-819 T/C and -592C/A) showed 3.63 and 3.52 higher relative mRNA expressions than controls, but poor survival of 984 and 1052 days than TT of 1359 days and AA of 1371 days.


CONCLUSIONS
Genetic variants of pro-inflammatory IL-18 which showed higher relative mRNA expressions have better survival. Genetic variants of anti-inflammatory IL-10 with higher relative mRNA expression showed decreased chances of survival.
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.|Department of Pharmacology and Therapeutics, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India.
Shailendra
S
Dwivedi
Department of Urology, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India.
Apul
A
Goel
Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, Uttar Pradesh, India.
Anil
A
Mandhani
Department of Pharmacology and Therapeutics, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India.
Sanjay
S
Khattri
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.
Praveen
P
Sharma
Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India.
Sanjeev
S
Misra
Department of Pharmacology and Therapeutics, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India.
Kamlesh Kumar
KK
Pant
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005500:Follow-Up Studies; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate
C508609:IL10 protein, human; D020382:Interleukin-18; D012333:RNA, Messenger; D016753:Interleukin-10
genetic variations; mRNA expression; pro- and anti-inflammatory interleukins (IL-18 and IL-10); prostate carcinoma; survival