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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

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Abstract

Objective

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.

Results

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%).

Conclusions

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Division of Molecular Genetics and Biochemistry, National Institute of Cancer Prevention and Research (ICMR), I-7, Sector-39, Noida, 201301, India

    Kapil Bandil, Pallavi Singhal & Mausumi Bharadwaj

  2. Dr. A.P.J. Abdul Kalam Technical University, Lucknow, UP, India

    Kapil Bandil & Mausumi Bharadwaj

  3. Research Department, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

    Atika Dogra

  4. Surgical Gynae Uro-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

    Sudhir K. Rawal

  5. Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi, India

    D. C. Doval

  6. R. G. Stone Urology and Laparoscopy Hospital, New Delhi, India

    Anil K. Varshney

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  1. Kapil Bandil
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Correspondence to Mausumi Bharadwaj.

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Bandil, K., Singhal, P., Dogra, A. et al. 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. Inflamm. Res. 66, 1085–1097 (2017). https://doi.org/10.1007/s00011-017-1088-5

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  • DOI: https://doi.org/10.1007/s00011-017-1088-5

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