Association of SNPs/haplotypes in promoter of TNF A and IL-10 gene together with life style factors in prostate cancer progression in Indian population
Levels of proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines play a key role in the progression of inflammation as well as cancer disease. We were investigating the potential association of single-nucleotide polymorphisms (SNPs)/haplotypes in proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines locus with the development of PCa in Indian population.
Materials and methods
We had genotyped 235 BPH/PCa samples (130 BPH and 105 cancer) along with 115 control samples for proinflammatory (TNF A −238G/A and −308G/A) and anti-inflammatory (IL-10 −1082A/G, −819C/T and −592C/A) cytokines SNPs in the gene promoter region using ARMS-PCR method.
Allelic frequencies of TNF A and IL-10 SNPs were found to be significantly associated with the risk of prostate cancer and BPH when compared to controls (p = 0.05). Further haplotypic analysis showed that two haplotypes of TNF A (AG and AA) and IL-10 gene (CCG and CTG) were serving as risk haplotypes for prostate cancer development. IL-10 risk haplotypes were found to be positively associated with aggressiveness of prostate cancer. We also noticed successively increasing percentage of TNF A and IL-10 risk haplotypes with life style habits like smoking (10 and 26%) and alcohol consuming (9 and 27%).
According to our data, TNF A −238G>A and IL-10 −1082A>G, −819C>T and −592C>A may be associated with the development of prostate cancer and BPH. We could also notice higher frequency of TNF A and IL-10 risk haplotypes in smoker and alcohol user. Interestingly, IL-10 risk haplotype was positively associated with aggressiveness of tumor. This information can be used for the early diagnosis of disease and to improve tissue-specific treatment’s efficacy which will be moving ultimately towards the discovery of personalized therapy.
KeywordsProstate cancer TNF A IL-10 Haplotype
The authors thank patients, their relatives, and clinicians for their support and cooperation. The study was supported by funds provided by NICPR-ICMR, Noida to MB.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 22.Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. Cold spring harbor laboratory press; 1989.Google Scholar
- 28.Horvat V, Sudarevic B, Cosic I, Milicevic N, Bosnjak S, Mandic S, et al. Lack of association between TNF-alpha promoter polymorphism and prostate carcinoma susceptibility in eastern Croatian population. Coll Antropol. 2014;37:1199–202.Google Scholar
- 39.Pacheco SO, Pacheco FJ, Zapata GM, Garcia JM, Previale CA, Cura HE, et al. Food habits, lifestyle factors, and risk of prostate cancer in Central Argentina: a case control study involving self-motivated health behavior modifications after diagnosis. Nutrients. 2016;8(7):1–22. doi: 10.3390/nu8070419.CrossRefGoogle Scholar