Research Article
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Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer

Year 2022, Volume: 12 Issue: 3, 1336 - 1344, 01.09.2022
https://doi.org/10.21597/jist.1107271

Abstract

The aim of this study is to evaluate the association of interleukin-4 (IL-4) gene intron 3 and interleukin-1 receptor antagonist (IL-1Ra) gene intron 2 variable number tandem repeat (VNTR) polymorphisms with bladder cancer (BC) susceptibility in Turkish population. A total of 75 BC patients and 126 healthy controls were included in this case-control study. Genotyping for the interested polymorphisms were analyzed through polymerase chain reaction (PCR). The strength of association between both IL-4 and IL-1Ra gene VNTRs and BC susceptibility was estimated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI). In the study, no statistically significant differences were determined in the allele distributions for either in IL-4 gene intron 3 VNTR (OR= 1.33; CI 0.704-2,41, p=0.390) or in IL-1Ra gene intron 2 VNTR polymorphisms (OR= 0.890; CI 0.569-1.394, p=0.346) between BC patients and control groups. The genotype distributions of IL-4 gene were estimated for RP1/RP2 (OR= 1.55; CI 0.11-7.74, p = 0.590) and RP1/RP1 (OR= 2.08; CI 0.48-9.06, p = 0.320), found no difference between BC and control groups. The genotype distributions of IL-1Ra gene were estimated for 2L (OR= 1.401; CI 0.753-2.610, p = 0.287) and 22 (OR=0.908; CI 0.252-3.276, p = 0.883) and found no difference between BC and control groups. This study suggest that there were no statistically significant differences determined either in genotype or allele distributions between BC patients and control groups for both IL-4 intron 3 VNTR and IL-1Ra intron 2 VNTR polymorphisms in Turkish population and therefore there was no association of these variants with BC risk in this population.

Supporting Institution

Scientific Research Project Unit of Kocaeli University

Project Number

2017-055-BAP-HD

References

  • Ahirwar D, Kesarwani P, Manchanda, PK, Mandhani, A, Mittal, RD, 2008. Anti- and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade, and bacillus Calmette-Guérin immunotherapy in bladder cancer. Cancer Genetics and Cytogenetics, 184(1):1–8.
  • Ahirwar D K, Agrahari A, Mandhani A, Mittal R D, 2009. Cytokine gene polymorphisms are associated with risk of urinary bladder cancer and recurrence after BCG immunotherapy. Biomarkers, 14(4):213-218.
  • Ahmed A, Abdelgadir R, Muddathir A, Elshibli EM, Elmula FI, 2006. Interleukin-4 intron 3 VNTR polymorphism gene in leukemic patients. Journal of Blood Disorders & Transfusion, 7(3):100357.
  • Bhayal AC, Krishnaveni D, Rao KPR, Kumar AR, Jyothy A, Nallari, P, et. al., 2015. Significant association of Interleukin4 Intron 3 VNTR Polymorphism with susceptibility to gastric cancer in a South Indian population from Telangana. PloS ONE, 10(9): e0138442.
  • Bid HK, Manchanda PK, Mittal R, 2006. Association of interleukin-1Ra gene polymorphism in patients with bladder cancer: case control study from North India. Urology, 67(5):1099-1104.
  • Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J, McNicholl J, Pociot F, Hardt C, D’Alfonso S, 1999. Cytokine gene polymorphism in human disease: on-line databases. Genes &Immunity, 1(1):3–19.
  • Briukhovetska D, Dörr J, Endres S, Libby P, Dinarello CA, Kobolt S, 2021. Interleukins in cancer: from biology to therapy. Nature Reviews Cancer, 21: 481-499.
  • Bozdogan ST, Erol B, Dursun A, Bozdoğan G, Dönmez I, Mungan NA, et. al., 2015. The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case–control study. World Journal of Urology, 33:389–395.
  • Cai L, Zhang JW, Xue XX, Wang ZG, Wang JJ, Tang SW, et. al., 2014. Meta-Analysis of Associations of IL1 Receptor Antagonist and Estrogen Receptor Gene Polymorphisms with Systemic Lupus Erythematosus Susceptibility. PLoS ONE, 9(10):e109712.
  • Cauci S, Di Santolo, M, Ryckman KK, Williams, SM, Banfi G, 2010. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status. BMC Medical Genetics,11(1):29.
  • Chu H, Ma L, Wang M, Shi D, Qin C, Yuan L. et al., 2012. The polymorphisms of IL-4, IL-4R and IL-13 genes and bladder cancer risk in a Chinese population: a case-control study. Molecular Biology Reports, 39:5349-57.
  • Dinarello CA, 2018. Overview of the IL-1 family in innate inflammation and acquired immunity, Immunological Reviews, 281 (1):8–27.
  • Duan Y, Pan C, Shi J, Chen H, Zhang S, 2014. Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk. Cancer cell international, 14 (1):131.
  • Elghoroury EA, Fadel FI, Farouk H, Elshamaa MF, Kamel S, Kandil D, et al., 2018. Association of variable number tandem repeats polymorphism in the IL-4 gene with end-stage renal disease in children. Egypt Journal of Medical Human Genetics, 19(3):191-195.
  • Garlanda C, Dinarello C, Mantovani A, 2013. The interleukin-1 family: back to the future. Immunity, 39(6):1003-1018.
  • Guo H, Callaway JB, Ting JP, 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature Medicine, 21:677-87.
  • Hallegua DS, Weisman MH, 2002. Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases. Annals of the Rheumatic Diseases, 61:960–967.
  • John A, Günes C, Bolenz C, Vidal-y-Sy S, Bauer AT, Schneider SW, et al., 2020. Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface. BMC Cancer, 20:1178. https://doi.org/10.1186/s12885-020-07548-z
  • Kok YY, Ong HH, Say YH, 2017. Interleukin-1 receptor antagonist and interleukin-4 genes variable number tandem repeats are associated with adiposity in Malaysian subjects. Journal of obesity, 2017: Article ID:4104137, doi: 10.1155/2017/4104137
  • Lewis AM, Varghese S, Xu H, Alexander HR, 2006. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. Journal of translational medicine, 4(1):48.
  • Madeb R, Messing EM, 2004. Gender, racial and age differences in bladder cancer incidence and mortality. Urologic Oncology, 22(2):86-92.
  • Makhlouf MM, Elhamid SMA, 2014. Expression of IL4 (VNTR intron 3) and IL10 (-627) genes polymorphisms in childhood immune thrombocytopenic purpura. Laboratory medicine, 45(3):211-219.
  • Mout R, Willemze R, Landegent JE, 1991. Repeat polymorphisms in the interleukin-4 (IL-4). Nucleic Acids Research, 19(13):3763.
  • Mungan NA, Kiemeney LA, van Dijck JA, van der Poel, HG, Witjes JA, 2000. Gender differences in stage distribution of bladder cancer. Urology, 55(3):368-371.
  • Mustea A, Sehouli J, Könsgen D, Stengel D, Sofroni D, Lichtenegger W, 2003. Interleukin 1 receptor antagonist (IL-1RA) polymorphism in women with cervical cancer. Anticancer Research, 23:1099-1102.
  • Oliveira JG, Duarte MC, Silva AE, 2012. IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-β pro-inflammatory cytokine is not. Molecular biology reports, 39(7):7617-7625.
  • Olver S, Apte S, Baz A, Kienzle N, 2007. The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?, Tissue Antigens, 69(4):293–298.
  • Sehouli J, Mustea A, Koensgen D, Chen FK, Lichtenegger W, 2003. Interleukin-1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer. Annals of oncology, 14(10):1501-1504, https://doi.org/10.1093/annonc/mdg413
  • Schneider L, Liu J, Zhang C, Azoitei A, Meessen S, Zheng X, Cremer C, Gorzelanny C, Kempe-Gonzales S, Brunner C, 2021. The Role of Interleukin-1-Receptor-Antagonist in Bladder Cancer Cell Migration and Invasion. International Journal of Molecular Sciences, 22:5875,
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F, 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA a Cancer Journal of Clinicians, 71(3):209-249. https://doi: 10.3322/caac.21660
  • Swain SL, Weinberg AD, English,M, Huston G, 1990. IL-4 directs the development of Th2-like helper effectors, The Journal of Immunology., 145(11):3796–3806.
  • Tao L, Qiu J, Jiang M, Song W, Yeh S, Yu H, et. al., 2016. Infiltrated T cells promote bladder cancer progression via increasing IL-1→ androgen receptor (AR)→ HIF-1α→ VEGFa signals, Molecular. Cancer Therapeutics, 15(8):943-1951.
  • Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, et. al.,1993. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Human Genetics, 91(4):173-176.
  • Tsai FJ, Chang CH, Chen CC, Hsia TC, 2005. Interleukin-4 gene intron-3 polymorphism is associated with transitional cell carcinoma of the urinary bladder. BJU International. 95:430–435.
  • Vamvakopoulos J, Green C, Metcalfe S, 2002. Genetic control of IL-1 I bioactivity through differential regulation of the IL-1 receptor antagonist. European Journal of Immunology, 32:2988–2996.
  • Worst TS, Reiner V, Gabriel U, Weiß C, Erben P, Martini T, Bolenz C, 2014. IL1RN and KRT13 Expression in bladder cancer: association with pathologic characteristics and smoking status. Advances in urology, 2014: Article ID:184602. https://doi.org/10.1155/2014/184602
  • Yang CM, Chen HC, Hou YY, Lee MC, Liou HH, Huang SJ, et al., 2014. A high IL-4 production diplotype is associated with an increased risk but better prognosis of oral and pharyngeal carcinomas, Archieves of Oral Biology, 59(1):35–46.
Year 2022, Volume: 12 Issue: 3, 1336 - 1344, 01.09.2022
https://doi.org/10.21597/jist.1107271

Abstract

Project Number

2017-055-BAP-HD

References

  • Ahirwar D, Kesarwani P, Manchanda, PK, Mandhani, A, Mittal, RD, 2008. Anti- and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade, and bacillus Calmette-Guérin immunotherapy in bladder cancer. Cancer Genetics and Cytogenetics, 184(1):1–8.
  • Ahirwar D K, Agrahari A, Mandhani A, Mittal R D, 2009. Cytokine gene polymorphisms are associated with risk of urinary bladder cancer and recurrence after BCG immunotherapy. Biomarkers, 14(4):213-218.
  • Ahmed A, Abdelgadir R, Muddathir A, Elshibli EM, Elmula FI, 2006. Interleukin-4 intron 3 VNTR polymorphism gene in leukemic patients. Journal of Blood Disorders & Transfusion, 7(3):100357.
  • Bhayal AC, Krishnaveni D, Rao KPR, Kumar AR, Jyothy A, Nallari, P, et. al., 2015. Significant association of Interleukin4 Intron 3 VNTR Polymorphism with susceptibility to gastric cancer in a South Indian population from Telangana. PloS ONE, 10(9): e0138442.
  • Bid HK, Manchanda PK, Mittal R, 2006. Association of interleukin-1Ra gene polymorphism in patients with bladder cancer: case control study from North India. Urology, 67(5):1099-1104.
  • Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J, McNicholl J, Pociot F, Hardt C, D’Alfonso S, 1999. Cytokine gene polymorphism in human disease: on-line databases. Genes &Immunity, 1(1):3–19.
  • Briukhovetska D, Dörr J, Endres S, Libby P, Dinarello CA, Kobolt S, 2021. Interleukins in cancer: from biology to therapy. Nature Reviews Cancer, 21: 481-499.
  • Bozdogan ST, Erol B, Dursun A, Bozdoğan G, Dönmez I, Mungan NA, et. al., 2015. The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case–control study. World Journal of Urology, 33:389–395.
  • Cai L, Zhang JW, Xue XX, Wang ZG, Wang JJ, Tang SW, et. al., 2014. Meta-Analysis of Associations of IL1 Receptor Antagonist and Estrogen Receptor Gene Polymorphisms with Systemic Lupus Erythematosus Susceptibility. PLoS ONE, 9(10):e109712.
  • Cauci S, Di Santolo, M, Ryckman KK, Williams, SM, Banfi G, 2010. Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status. BMC Medical Genetics,11(1):29.
  • Chu H, Ma L, Wang M, Shi D, Qin C, Yuan L. et al., 2012. The polymorphisms of IL-4, IL-4R and IL-13 genes and bladder cancer risk in a Chinese population: a case-control study. Molecular Biology Reports, 39:5349-57.
  • Dinarello CA, 2018. Overview of the IL-1 family in innate inflammation and acquired immunity, Immunological Reviews, 281 (1):8–27.
  • Duan Y, Pan C, Shi J, Chen H, Zhang S, 2014. Association between interleukin-4 gene intron 3 VNTR polymorphism and cancer risk. Cancer cell international, 14 (1):131.
  • Elghoroury EA, Fadel FI, Farouk H, Elshamaa MF, Kamel S, Kandil D, et al., 2018. Association of variable number tandem repeats polymorphism in the IL-4 gene with end-stage renal disease in children. Egypt Journal of Medical Human Genetics, 19(3):191-195.
  • Garlanda C, Dinarello C, Mantovani A, 2013. The interleukin-1 family: back to the future. Immunity, 39(6):1003-1018.
  • Guo H, Callaway JB, Ting JP, 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature Medicine, 21:677-87.
  • Hallegua DS, Weisman MH, 2002. Potential therapeutic uses of interleukin 1 receptor antagonists in human diseases. Annals of the Rheumatic Diseases, 61:960–967.
  • John A, Günes C, Bolenz C, Vidal-y-Sy S, Bauer AT, Schneider SW, et al., 2020. Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface. BMC Cancer, 20:1178. https://doi.org/10.1186/s12885-020-07548-z
  • Kok YY, Ong HH, Say YH, 2017. Interleukin-1 receptor antagonist and interleukin-4 genes variable number tandem repeats are associated with adiposity in Malaysian subjects. Journal of obesity, 2017: Article ID:4104137, doi: 10.1155/2017/4104137
  • Lewis AM, Varghese S, Xu H, Alexander HR, 2006. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. Journal of translational medicine, 4(1):48.
  • Madeb R, Messing EM, 2004. Gender, racial and age differences in bladder cancer incidence and mortality. Urologic Oncology, 22(2):86-92.
  • Makhlouf MM, Elhamid SMA, 2014. Expression of IL4 (VNTR intron 3) and IL10 (-627) genes polymorphisms in childhood immune thrombocytopenic purpura. Laboratory medicine, 45(3):211-219.
  • Mout R, Willemze R, Landegent JE, 1991. Repeat polymorphisms in the interleukin-4 (IL-4). Nucleic Acids Research, 19(13):3763.
  • Mungan NA, Kiemeney LA, van Dijck JA, van der Poel, HG, Witjes JA, 2000. Gender differences in stage distribution of bladder cancer. Urology, 55(3):368-371.
  • Mustea A, Sehouli J, Könsgen D, Stengel D, Sofroni D, Lichtenegger W, 2003. Interleukin 1 receptor antagonist (IL-1RA) polymorphism in women with cervical cancer. Anticancer Research, 23:1099-1102.
  • Oliveira JG, Duarte MC, Silva AE, 2012. IL-1ra anti-inflammatory cytokine polymorphism is associated with risk of gastric cancer and chronic gastritis in a Brazilian population, but the TNF-β pro-inflammatory cytokine is not. Molecular biology reports, 39(7):7617-7625.
  • Olver S, Apte S, Baz A, Kienzle N, 2007. The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?, Tissue Antigens, 69(4):293–298.
  • Sehouli J, Mustea A, Koensgen D, Chen FK, Lichtenegger W, 2003. Interleukin-1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer. Annals of oncology, 14(10):1501-1504, https://doi.org/10.1093/annonc/mdg413
  • Schneider L, Liu J, Zhang C, Azoitei A, Meessen S, Zheng X, Cremer C, Gorzelanny C, Kempe-Gonzales S, Brunner C, 2021. The Role of Interleukin-1-Receptor-Antagonist in Bladder Cancer Cell Migration and Invasion. International Journal of Molecular Sciences, 22:5875,
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F, 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA a Cancer Journal of Clinicians, 71(3):209-249. https://doi: 10.3322/caac.21660
  • Swain SL, Weinberg AD, English,M, Huston G, 1990. IL-4 directs the development of Th2-like helper effectors, The Journal of Immunology., 145(11):3796–3806.
  • Tao L, Qiu J, Jiang M, Song W, Yeh S, Yu H, et. al., 2016. Infiltrated T cells promote bladder cancer progression via increasing IL-1→ androgen receptor (AR)→ HIF-1α→ VEGFa signals, Molecular. Cancer Therapeutics, 15(8):943-1951.
  • Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, et. al.,1993. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Human Genetics, 91(4):173-176.
  • Tsai FJ, Chang CH, Chen CC, Hsia TC, 2005. Interleukin-4 gene intron-3 polymorphism is associated with transitional cell carcinoma of the urinary bladder. BJU International. 95:430–435.
  • Vamvakopoulos J, Green C, Metcalfe S, 2002. Genetic control of IL-1 I bioactivity through differential regulation of the IL-1 receptor antagonist. European Journal of Immunology, 32:2988–2996.
  • Worst TS, Reiner V, Gabriel U, Weiß C, Erben P, Martini T, Bolenz C, 2014. IL1RN and KRT13 Expression in bladder cancer: association with pathologic characteristics and smoking status. Advances in urology, 2014: Article ID:184602. https://doi.org/10.1155/2014/184602
  • Yang CM, Chen HC, Hou YY, Lee MC, Liou HH, Huang SJ, et al., 2014. A high IL-4 production diplotype is associated with an increased risk but better prognosis of oral and pharyngeal carcinomas, Archieves of Oral Biology, 59(1):35–46.
There are 37 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Biyoloji / Biology
Authors

Fikriye Polat 0000-0002-5414-2501

Günsel Bingöl 0000-0001-9834-0019

Songül Budak Diler 0000-0002-7156-583X

Project Number 2017-055-BAP-HD
Early Pub Date August 26, 2022
Publication Date September 1, 2022
Submission Date April 21, 2022
Acceptance Date June 30, 2022
Published in Issue Year 2022 Volume: 12 Issue: 3

Cite

APA Polat, F., Bingöl, G., & Budak Diler, S. (2022). Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer. Journal of the Institute of Science and Technology, 12(3), 1336-1344. https://doi.org/10.21597/jist.1107271
AMA Polat F, Bingöl G, Budak Diler S. Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer. J. Inst. Sci. and Tech. September 2022;12(3):1336-1344. doi:10.21597/jist.1107271
Chicago Polat, Fikriye, Günsel Bingöl, and Songül Budak Diler. “Association of IL-4 and IL-1 Ra Gene Polymorphisms With the Risk of Bladder Cancer”. Journal of the Institute of Science and Technology 12, no. 3 (September 2022): 1336-44. https://doi.org/10.21597/jist.1107271.
EndNote Polat F, Bingöl G, Budak Diler S (September 1, 2022) Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer. Journal of the Institute of Science and Technology 12 3 1336–1344.
IEEE F. Polat, G. Bingöl, and S. Budak Diler, “Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer”, J. Inst. Sci. and Tech., vol. 12, no. 3, pp. 1336–1344, 2022, doi: 10.21597/jist.1107271.
ISNAD Polat, Fikriye et al. “Association of IL-4 and IL-1 Ra Gene Polymorphisms With the Risk of Bladder Cancer”. Journal of the Institute of Science and Technology 12/3 (September 2022), 1336-1344. https://doi.org/10.21597/jist.1107271.
JAMA Polat F, Bingöl G, Budak Diler S. Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer. J. Inst. Sci. and Tech. 2022;12:1336–1344.
MLA Polat, Fikriye et al. “Association of IL-4 and IL-1 Ra Gene Polymorphisms With the Risk of Bladder Cancer”. Journal of the Institute of Science and Technology, vol. 12, no. 3, 2022, pp. 1336-44, doi:10.21597/jist.1107271.
Vancouver Polat F, Bingöl G, Budak Diler S. Association of IL-4 and IL-1 Ra Gene Polymorphisms with the Risk of Bladder Cancer. J. Inst. Sci. and Tech. 2022;12(3):1336-44.