TSitologiya i Genetika 2020, vol. 54, no. 5, 114-116
Cytology and Genetics 2020, vol. 54, no. 5, 487–492, doi: https://www.doi.org/10.3103/S0095452720050138

Association of IL-1RA and IL-4 gene vntrs with susceptibility to prostate cancer in turkish population

Bingöl G., Polat F., Diler S.B.

  1. Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Ankara Yıldırım Beyazıt University, Ankara, Turkey
  2. Department of Mathematics and Science Education, Faculty of Education, Kocaeli University, Kocaeli, Turkey
  3. Department of Biotechnology, Faculty of Science and Literature, Nigde Omer Halisdemir University, Nigde, Turkey

Prostate cancer (PCa) is a very common type of cancer among men. It was revealed that Interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1Ra) genes had important functions such as development of prostate cells or regulating the inflammatory processes. The important role of cytokines in inflammatory mechanisms leads to the possibility that polymorphisms of these genes may contribute to the formation of prostate cancer. In this study, we aimed to investigate the association of variable number tandem repeat (VNTR) polymorphisms in the IL-1Ra and IL-4 genes with PCa in Turkish population. 70 prostate cancer patients and 110 healthy controls were involved in a case-control study. Genotype distributions and allele frequencies for the IL-1Ra intron 2 (rs2234663) and IL-4 intron 3 (rs79071878) VNTR polymorphisms were analyzed by using PCR technique. No statistically significant association was identified for both IL-1Ra intron 2 and IL-4 intron 3 polymorphisms between PCa patients and controls (P> 0.05). IL-1Ra intron 2 and IL-4 intron-3 VNTR polymorphisms were not found to be risk factors in prostate cancer and its development in Turkish population.

Keywords: prostate cancer, variable number tandem repeats, interleukin-1 receptor antagonist, interleukin-4, polymorphism

TSitologiya i Genetika
2020, vol. 54, no. 5, 114-116

Current Issue
Cytology and Genetics
2020, vol. 54, no. 5, 487–492,
doi: 10.3103/S0095452720050138

Full text and supplemented materials

References

1. Köse, M.R., Başara, B.B., Güler, C., Soytuta, I., Aygün, A., and Özdemir, T.A., Republic of Turkey Ministry of Health, Health Statistics Yearbook 2015, Ankara, Turkey, General Directorate of Health Research, Ministry of Health, 2016.

2. Kgatle, M.M., Kalla, A.A., Islam, M.M., Sathekge, M., and Moorad, R., Prostate cancer: epigenetic alterations, risk factors, and therapy, Prostate Cancer, 2016, vol. 2016, p. 111.

3. Tindall, E.A., Haye, V.M., and Petersen, D.C., Inflammatory genetic markers of prostate cancer risk, Cancers, 2010, vol. 2, no. 2, pp. 1198–1120.

4. Howell, W.M., Calder, P.C., and Grimble, R.F., Gene polymorphisms, inflammatory diseases and cancer, Proc. Nutr. Soc., 2002, vol. 61, pp. 447–456.

5. Patterson, D., Jones, C., Hart, I., Bleskan, J., Berger, R., Geyer, D., Eisenberg, S.P., Smith, M.F., Jr., and Arend, W.P., The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region, Genomics, 1993, vol. 15, no. 1, pp. 173–176.https://doi.org/10.1006/geno.1993.1025

6. Steinkasserer, A., Spurr, N.K., Cox, S., Jeggo, P., and Sim, R.B., The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14–q21, in the region of the IL-1α and IL-1β loci, Genomics, 1992, vol. 13, no. 3, pp. 654–657.

7. Tarlow, J.K., Blakemore, A.I., Lennard, A., Solari, R., Hughes, H.N., Steinkasserer, A., et al., Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat, Hum. Genet., 1993, vol. 91, no. 4, pp. 403–404.

8. Steinkasserer, A., Koelble, K., and Sim, R.B., Length variation within intron 2 of the human IL-1 receptor antagonist protein gene (IL1RN), Nucleic Acids Res., 1991, vol. 19, no. 18, p. 5095.

9. Zhang, Y., Liu, C., Peng, H., Zhang, J., and Feng, Q., IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis, PLoS One, 2012, vol. 7, no. 9, p. e46017.

10. Arinob,u. Y., Atamas, S.P., Otsuka, T., Niiro, H., Yamaoka, K., Mitsuyasu, H., Niho, Y., Hamasaki, N., White, B., and Izuhara, K., Antagonistic effects of an alternative splice variant of human IL-4, IL-4d2, on IL-4 activities in human monocytes and B cells, Cell. Immunol., 1999, vol. 191, pp. 161–167. https://doi.org/10.1006/cimm.1998.1431

11. Olver, S., Apte, S., Baz, A., and Kienzle, N., The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?, Tissue Antigens, 2007, vol. 69, no. 4, pp. 293–298.

12. Kramer, G., Steiner, G.E., Handisurya, A., Stix, U., Haitel, A., Knerer, B., Gessl, A., Lee, Ch., and Marberger, M., Increased expression of lymphocyte derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation, Prostate, 2002, vol. 52, no. 1, pp. 43–58. https://doi.org/10.1002/pros.10084

13. Arai, N., Nomura, D., Villaret, D., Malefijt, R.D., Seiki, M., Yoshida, M., Minoshima, S., Fukuyama, R., Maekawa, M., and Kudoh, J., Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression, J. Immun., 1989, vol. 142, no. 1, pp. 274–282.

14. Witte, J.S., Goddard, K.A., Conti, D.V., Elston, R.C., Lin, J., Suarez, B.K., Broman, K.W., Burmester, J.K., Weber, J.L., and Catalon,a, W.J., Genome-wide scan for prostate cancer–aggressiveness loci, Am. J. Hum. Genet., 2000, vol. 67, no. 1, pp. 92–99. https://doi.org/10.1086/302960

15. Mout, R., Willemze, R., and Landegent, J.E., Repeat polymorphisms in the interleukin-4 (IL-4), Nucleic Acids Res., 1991, vol. 19, no. 13, p. 3763.

16. Bhayal, A.C., Krishnaveni, D., Rao, K.P., Kumar, A.R., Jyothy, A., Nallari, P., and Venkateshwari, A., Significant association of interleukin 4 Iintron 3 VNTR polymorphism with susceptibility to gastric cancer in a South Indian population from Telangana, PLos One, 2015, vol. 10, no. 9, e0138442. https://doi.org/10.1371/journal.pone.0138442

17. Susceptibility to Gastric Cancer in a South Indian Population from Telangana, PLoS One, 2015, vol. 10, no. 9, e0138442.

18. Tsai, F.J., Chang, C.H., Chen, C.C., Hsia, T.C., Chen, H.Y., and Chen, W.C., Interleukin-4 gene intron-3 polymorphism is associated with transitional cell carcinoma of the urinary bladder, BJU Int., 2005, vol. 95, no. 3, pp. 432–435.

19. Diler, S.B. and Öden, A., The T-786C, G894T, and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases, Russ. J. Genet., 2016, vol. 52, no. 2, pp. 220–225.

20. Bid, H.K., Manchanda, P.K., and Mittal, R.D., Association of interleukin-1Ra gene polymorphism in patients with bladder cancer: case control study from North India, Urology, 2006, vol. 67, no. 5, pp. 1099–104.

21. Yu, S.J., Kim, H.S., Cho, S.W., and Sohn, J., IL-4 inhibits proliferation of renal carcinoma cells by increasing the expression of p21WAF1 and IRF-1, Exp. Mol. Med., 2004, vol. 36, no. 4, p. 372.

22. Myers, J.N., Yasumura, S., Suminami, Y., Hirabayashi, H., Lin, W., Johnson, J.T., Lotze, M.T., and Whiteside, T.L., Growth stimulation of human head and neck squamous cell carcinoma cell lines by interleukin 4, Clin. Cancer Res., 1996, vol. 2, no. 1, pp. 127–135.

23. Nakashima, H., Miyake, K., Inoue, Y., Shimizu, S., Akahoshi, M., Tanaka, Y., Otsuka, T., and Harada, M., Association between IL-4 genotype and IL-4 production in the Japanese population, Gen. Immun., 2002, vol. 3, no. 2, pp. 107–109. https://doi.org/10.1038/sj.gene.6363830

24. Salimi, S., Mohammadoo-Khorasani, M., Yaghmaei, M., Mokhtari, M., and Moossavi, M., Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia, Biomed. Res. İnt., 2014, vol. 2014, p. 497031.

25. Konwar, R., Chaudhary, P., Kumar, S., Mishra, D., Chattopadhyay, N., and Bid, H.K., Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women, Oncol. Res., 2009, vol. 17, no. 8, pp. 367–372.

26. Shekari, M., Kordi-Tamandani, D.M., MalekZadeh, K., Sobti, R.C., Karimi, S., and Suri, V., Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of cervical carcinoma, Am. J. Clin. Oncol., 2012, vol. 35, no. 6, pp. 514–519.

27. Bozdoğan, S.T., Erol, B., Dursun, A., Bozdoğan, G., Dönmez, I., Mungan, N.A., and Seydaoglu, G., The IL-1RN and IL-4 gene polymorphisms are potential genetic markers of susceptibility to bladder cancer: a case–control study, World J. Urol., 2015, vol. 33, no. 3, pp. 389–395.

28. Kesarwani, P., Ahirwar, D.K., Mandhani, A., and Mittal, R.D., Association between –174 G/C promoter polymorphism of the interleukin-6 gene and progression of prostate cancer in North Indian population, DNA Cell Biol., 2008, vol. 27, no. 9, pp. 505–510.

29. Carvalho, M.A., Salles, T.S.I., and Saad, S.T.O., The association of cytokine gene polymorphisms with febrile non-hemolytic transfusion reaction in multitransfused patients, Trans. Med., 2006, vol. 16, pp. 184–191.

30. Hu, Z., Shao, M., Chen, Y., Zhou, J., Qian, J., Xu, L., Ma, H., Wang, X., Xu, Y., Lu, D., and Shen, H., Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer, Cancer Lett., 2006, vol. 236, no. 2, pp. 269–275. https://doi.org/10.1016/j.canlet.2005.05.015

31. Sehouli, J., Mustea, A., Koensgen, D., Chen, F.K., and Lichtenegger, W., Interleukin- 1 receptor antagonist gene polymorphism is associated with increased risk of epithelial ovarian cancer, Ann. Oncol., 2003, vol. 14, no. 10, pp. 1501–1504.

32. Mittal, R.D., Mishra, D.K., Bid, H.K., and Mandhani, A., Interleukin-1 receptor antagonist polymorphism in patients with prostate cancer and benign prostatic hyperplasia: a case control study from north India, Urol. Oncol., 2004, vol. 4, pp. 131–134.

33. Ricote, M., Garcia-Tunon, I., Bethencourt, F.R., Fraile, B., Paniagua, R., and Royuela, M., Interleukin1 (IL-1α and IL-1β) and its receptors (IL-1RI, IL-1RII, and IL-1Ra) in prostate carcinoma, Cancer, 2004, vol. 100, no. 7, pp. 1388–1396