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ISSN: 1426-3912
Central European Journal of Immunology
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1/2020
vol. 45
 
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abstract:
Clinical immunology

Polymorphisms of genes encoding cytokines predict the risk of high-grade bladder cancer and outcomes of BCG immunotherapy

Wojciech Krajewski
1
,
Lidia Karabon
1, 2
,
Anna Partyka
2
,
Anna Tomkiewicz
2
,
Sławomir Poletajew
3
,
Andrzej Tukiendorf
4
,
Anna Kołodziej
1
,
Romuald Zdrojowy
1

  1. Department of Urology and Urological Oncology, Wroclaw Medical University, Wroclaw, Poland
  2. Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland
  3. Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland
  4. Department of Social Medicine, Wroclaw Medical University, Wroclaw, Poland
(Centr Eur J Immunol 2020; 45 (1): 37-47)
DOI: https://doi.org/10.5114/ceji.2020.94674
Online publish date: 2020/04/06
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Introduction
The present study investigated the association of cytokines genes polymorphisms (IL-2, IL-8 and IL-18) and polymorphisms in genes encoding molecules related to the differentiation of Th17 subpopulation (IL-17 and IL-23R) with the risk of bladder cancer (BC) and response to BCG immunotherapy.

Material and methods
Altogether, 175 BC patients treated with BCG due to high-grade non-muscle invasive tumors and 207 healthy individuals were genotyped for the following polymorphisms: IL-17A-197G>A (rs2275913); IL-17F+7488T>C (rs763780); IL-23Rc.309C>A (rs10889677); IL-23Rc.1142G>A (rs11209026); IL-2-330T>G (rs2069762), IL-8-251A>T (rs4073), and IL-18-137G>C (rs187238) using the TaqMan SNP genotyping assays.

Results
The IL-23Rc.-309C>A[A] allele was associated with the risk of BC (OR: 1.42, p = 0.03). Moreover, heterozygocities for IL-17A-197G>A[GA] and IL-18-137G>C[GC] increased the risk of BC, as compared to both homozygotes (OR: 1.67, p = 0.01 and OR: 1.84, p = 0.008, respectively). The IL-18-137G>C[GC] heterozygous patients had the highest risk of tumor recurrence and progression, and the worst recurrence-free and progression-free survival. Homozygous IL-17A-197G>A[GG] patients presented the best recurrence-free survival, while IL-17A-197G>A[AA] patients had 1.8-fold higher risk of recurrence.

Conclusions
The present study highlighted the importance of IL-17, IL-18, and IL-23R gene polymorphisms for BC susceptibility and BCG immunotherapy outcomes. It may help to identify appropriate candidates for early radical treatment.

keywords:

gene polymorphisms, non-muscle-invasive bladder cancer, bacillus Calmette-Guerin, recurrence, progression
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