Цитологія і генетика 2020, том 54, № 5, 114-116
Cytology and Genetics 2020, том 54, № 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

РЕЗЮМЕ. Рак простати (РП) – це дуже поширений тип раку серед чоловіків. Було виявлено, що гени антагоністів рецептора інтерлейкіну-4 (IL-4) та інтерлейкіну-1 (IL-1Ra) виконують важливі функції, такі як розвиток клітин простати або регуляція запальних процесів. Важлива роль цитокінів у запальних механізмах створює можливість для того, щоб поліморфізми цих генів сприяли виникненню раку простати. Метою нашого дослідження було вивчення взаємозв’язку між поліморфізмами змінного числа тандемних повторів (VNTR) у генах IL-1Ra та IL-4 і РП у населенні Туреччини. Учасниками дослідження типу «випадок-контроль» були 70 пацієнтів з раком простати і 110 здорових осіб контрольної групи. Розподіл генотипів і частоти алелів для поліморфізмів VNTR інтрона IL-1Ra 2 (rs2234663) та інтрона IL-4 3 (rs79071878) проаналізували за допомогою технології ПЛР. Не було виявлено жодного статистично значного взаємозв’язку між пацієнтами з РП та контрольними особами ні для поліморфізмів інтрона IL-1Ra 2, ні для інтрона IL-4 3 (P> 0,05). Було виявлено, що поліморфізми VNTR інтрона IL-1Ra 2 та інтрона IL-4 3 VNTR не є факторами ризику виникнення раку простати та його розвитку у населення Туреччини.

Ключові слова: рак простати, змінне число тандемних повторів, антагоніст рецептора інтерлейкіну-1, інтерлейкін-4, поліморфізм

Цитологія і генетика
2020, том 54, № 5, 114-116

Current Issue
Cytology and Genetics
2020, том 54, № 5, 487–492,
doi: 10.3103/S0095452720050138

Повний текст та додаткові матеріали

Цитована література

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