Sabet, SalwaKhalaf El-Sayed, ShroukTaha Mohamed, HossamEl-Shinawi, MohamedM. Mohamed, Mona2020-02-292020-02-2920171. Bray F, Ren JS, Masuyer E, etal. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013(132): 1133–1145. 2. Pharoah PD, Dunning AM, Ponder BA, et al. Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 2004; 4: 850–860. 3. Dong LM, Potter JD, White E, et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 2008; 299: 2423–2436. 4. Mohamed MM. Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: a mechanism mediated by IL-8 signaling pathway. Cell Commun Signal 2012; 10: 3. 5. Mohamed MM, Cavallo-Medved D and Sloane BF. Human monocytes augment invasiveness and proteolytic activity of inflammatory breast cancer. Biol Chem 2008; 389: 1117–1121. 6. Mohamed MM, Sabet S, Peng DF, et al. Promoter hypermethylation and suppression of glutathione peroxidase 3 are associated with inflammatory breast carcinogenesis. Oxid Med Cell Longev 2014; 2014: 787195. 7. Nouh MA, Mohamed MM, El-Shinawi M, et al. Cathepsin B: a potential prognostic marker for inflammatory breast cancer. J Transl Med 2011; 9: 1. 8. Victor BC, Anbalagan A, Mohamed MM, et al. Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion. Breast Cancer Res 2011; 13: R115. 9. Mohamed MM, El-Ghonaimy EA, Nouh MA, et al. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. Int J Biochem Cell Biol 2014; 46: 138–147. 10. Kundu N, Beaty TL, Jackson MJ, et al. Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer. J Natl Cancer Inst 1996; 88: 536–541. 11. Huang S, Xie K, Bucana CD, et al. Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis. Clin Cancer Res 1996; 2: 1969–1979. 12. Stearns ME, Rhim J and Wang M. Interleukin 10 (IL-10) inhibition of primary human prostate cell-induced angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and inhibition of matrix metalloproteinase (MMP)-2/ MMP-9 secretion. Clin Cancer Res 1999; 5: 189–196. 13. Di Carlo E, Coletti A, Modesti A, et al. Local release of interleukin-10 by transfected mouse adenocarcinoma cells exhibits pro- and anti-inflammatory activity and results in a delayed tumor rejection. Eur Cytokine Netw 1998; 9: 61–68. 14. Kaufman HL, Rao JB, Irvine KR, et al. Interleukin-10 enhances the therapeutic effectiveness of a recombinant poxvirus-based vaccine in an experimental murine tumor model. J Immunother 1999; 22: 489–496. 15. Paul S, Biswas A, Sasmal K, et al. IL-10 alters prolactin receptor activity emulating that during breast cancer. Cytokine 2010; 51: 144–150. 16. Moore KW, O’Garra A, De Waal Malefyt R, et al. Interleukin-10. Ann Rev Immunol 1993; 11: 165–190. 17. Haddad JJ, Saade NE and Safieh-Garabedian B. Interleukin-10 and the regulation of mitogen-activated protein kinases: are these signalling modules targets for the anti-inflammatory action of this cytokine? Cell Signal 2003; 15: 255–267. 18. De Waal Malefyt R, Haanen J, Spits H, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 1991; 174: 915–924. 19. Hamidullah Changkija B and Konwar R. Role of interleukin-10 in breast cancer. Breast Cancer Res Treat 2012; 133: 11–21. 20. Haukim N, Bidwell JL, Smith AJ, et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun 2002; 3: 313–330. 21. Roh JW, Kim MH, Seo SS, et al. Interleukin-10 promoter polymorphisms and cervical cancer risk in Korean women. Cancer Lett 2002; 184: 57–63. 22. Howell WM and Rose-Zerilli MJ. Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutr 2007; 137: 194S–199S. 23. Niu YM, Du XY, Cai HX, et al. Increased risks between interleukin-10 gene polymorphisms and haplotype and head and neck cancer: a meta-analysis. Sci Rep 2015; 5: 17149. 24. You Y, Du X, Fan M, et al. Association between IL-10 polymorphisms (−1082A/G, −592A/C and −819T/C) and oral cancer risk. Int J Clin Exp Med 2015; 8: 13187–13194. 25. Vairaktaris E, Yapijakis C, Serefoglou Z, et al. The interleukin-10 (−1082A/G) polymorphism is strongly associated with increased risk for oral squamous cell carcinoma. Anticancer Res 2008; 28: 309–314. 26. Howell WM, Turner SJ, Bateman AC, et al. IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun 2001; 2: 25–31. 10 Tumor Biology 27. McCarron SL, Edwards S, Evans PR, et al. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 2002; 62: 3369–3372. 28. Horvat V, Mandic S, Marczi S, et al. Association of IL-1β and IL-10 polymorphisms with prostate cancer risk and grade of disease in Eastern Croatian population. Coll Antropol 2015; 39: 393–400. 29. Li C, Tong W, Liu B, et al. The −1082A>G polymorphism in promoter region of interleukin-10 and risk of digestive cancer: a meta-analysis. Sci Rep 2014; 4: 5335. 30. Stanczuk GA, Sibanda EN, Perrey C, et al. Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int J Cancer 2001; 94: 792–794. 31. Lan X, Lan T and Faxiang Q. Interleukin-10 promoter polymorphism and susceptibility to lung cancer: a systematic review and meta-analysis. Int J Clin Exp Med 2015; 8: 15317–15328. 32. Ahirwar D, Mandhani A and Mittal RD. Interleukin-10 G-1082A and C-819T polymorphisms as possible molecular markers of urothelial bladder cancer. Arch Med Res 2009; 40: 97–102. 33. Breen EC, Boscardin WJ, Detels R, et al. Non-Hodgkin’s B cell lymphoma in persons with acquired immunodeficiency syndrome is associated with increased serum levels of IL10, or the IL10 promoter -592 C/C genotype. Clin Immunol 2003; 109: 119–129. 34. Ni J, Ye Y, Teng F, et al. Interleukin 10 polymorphisms and cervical cancer risk: a meta-analysis. Int J Gynecol Cancer 2013; 23: 126–133. 35. Smith KC, Bateman AC, Fussell HM, et al. Cytokine gene polymorphisms and breast cancer susceptibility and prognosis. Eur J Immunogenet 2004; 31: 167–173. 36. Kong F, Liu J, Liu Y, et al. Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population. J Exp Clin Cancer Res 2010; 29: 72. 37. AlSuhaibani ES, Kizilbash NA, Malik S, et al. Polymorphisms in promoter regions of IL-6 and IL-10 genes in breast cancer: a case-control study. Genet Mol Res 2016; 15: 15017360. 38. Yu KD, Chen AX, Yang C, et al. The associations between two polymorphisms in the interleukin-10 gene promoter and breast cancer risk. Breast Cancer Res Treat 2012; 131: 27–31. 39. Vinod C, Jyothy A, Vijay Kumar M, et al. A common SNP of IL-10 (−1082A/G) is associated with increased risk of premenopausal breast cancer in South Indian women. Iran J Cancer Prev 2015; 8: e3434. 40. Giordani L, Bruzzi P, Lasalandra C, et al. Association of breast cancer and polymorphisms of interleukin-10 and tumor necrosis factor-alpha genes. Clin Chem 2003; 49: 1664–1667. 41. Wang Z, Liu QL, Sun W, et al. Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk. Croat Med J 2014; 55: 638–646. 42. Langsenlehner U, Krippl P, Renner W, et al. Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 2005; 90: 113–115. 43. Ibrahim AS, Khaled HM, Mikhail NN, et al. Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014; 2014: 18. 44. Badawy A, Abdalla HA, Mahmoud SA, et al. Association of IL-6 and IL-10 genes polymorphisms with breast cancer in Egyptian women. Bull Egypt Soc Physiol Sci 2012; 32: 125–140. 45. Shih CM, Lee YL, Chiou HL, et al. The involvement of genetic polymorphism of IL-10 promoter in non-small cell lung cancer. Lung Cancer 2005; 50: 291–297. 46. Hubacek JA, Pikhart H, Peasey A, et al. Nobody is perfect: comparison of the accuracy of PCR-RFLP and KASP method for genotyping. ADH1B and FTO polymorphisms as examples. Folia Biol 2015; 61: 156–160. 47. Makhmudi A, Sadewa AH, Aryandono T, et al. Effects of MTHFR c.677C>T, F2 c.20210G>A and F5 Leiden polymorphisms in gastroschisis. J Invest Surg 2016; 29: 88–92. 48. Hussain SR, Ahmad MK, Mahdi AA, et al. Association of interleukin-10 (A1082G) gene polymorphism with oral squamous cell carcinoma in north Indian population. J Genet 2016; 95: 249–255. 49. Korobeinikova E, Myrzaliyeva D, Ugenskiene R, et al. The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients. BMC Genet 2015; 16: 70. 50. Gunadi, Dwihantoro A, Iskandar K, et al. Accuracy of polymerase chain reaction-restriction fragment length polymorphism for RET rs2435357 genotyping as Hirschsprung risk. J Surg Res 2016; 203: 91–94. 51. El-Shinawi M, Mohamed HT, El-Ghonaimy EA, et al. Human cytomegalovirus infection enhances NF-κΒ/p65 signaling in inflammatory breast cancer patients. PloS ONE 2013; 8: e55755. 52. Back LK, Farias TD, Da Cunha PA, et al. Functional polymorphisms of interleukin-18 gene and risk of breast cancer in a Brazilian population. Tissue Antigens 2014; 84: 229–233. 53. Todd JH, Dowle C, Williams MR, et al. Confirmation of a prognostic index in primary breast cancer. Br J Cancer 1987; 56: 489–492. 54. Kingo K, Ratsep R, Koks S, et al. Influence of genetic polymorphisms on interleukin-10 mRNA expression and psoriasis susceptibility. J Dermatol Sci 2005; 37: 111–113. 55. Crawley E, Kay R, Sillibourne J, et al. Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 1999; 42: 1101–1108. 56. Hoffmann SC, Stanley EM, Darrin Cox E, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 2001; 72: 1444–1450. 57. Settin AA, Hassan HA, El-Baz RA, et al. Association of cytokine gene polymorphisms with psoriasis in cases from the Nile Delta of Egypt. Indian J Dermatol 2011; 56: 272–277. 58. Talaat RM, Dondeti MF, El-Shenawy SZ, et al. Association between IL-10 gene promoter polymorphism and hepatitis B viral infection in an Egyptian population. Biochem Genet 2014; 52: 387–402. 59. Talaat RM, Ashour ME, Bassyouni IH, et al. Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet’s disease. Immunobiology 2014; 219: 573–582. 60. Badr El-Din NK, Settin A, Ali N, et al. Cytokine gene polymorphisms in Egyptian cases with brain tumors. J Egypt Natl Cancer Inst 2009; 21: 101–106. Sabet et al. 11 61. Wei YS, Kuang XH, Zhu YH, et al. Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal carcinoma. Tissue Antigens 2007; 70: 12–17. 62. Ni P, Xu H, Xue H, et al. A meta-analysis of interleukin-10–1082 promoter polymorphism associated with gastric cancer risk. DNA Cell Biol 2012; 31: 582–591. 63. Wang J, Ding Q, Shi Y, et al. The interleukin-10–1082 promoter polymorphism and cancer risk: a meta-analysis. Mutagenesis 2012; 27: 305–312. 64. Abdolrahim-Zadeh H, Hakkakian N, Asadollahi R, et al. Interleukin-10 promoter polymorphisms and breast cancer risk in Iranian women. IJI 2005; 2: 158–165. 65. Balasubramanian SP, Azmy IA, Higham SE, et al. Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review. BMC Cancer 2006; 6: 188. 66. Kube D, Platzer C, von Knethen A, et al. Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt’s lymphoma cell lines. Cytokine 1995; 7: 1–7. 67. Romano-Spica V, Georgiou P, Suzuki H, et al. Role of ETS1 in IL-2 gene expression. J Immunol 1995; 154: 2724–2732. 68. Yu Z, Liu Q, Huang C, et al. The interleukin 10–819C/T polymorphism and cancer risk: a huge review and metaanalysis of 73 studies including 15,942 cases and 22,336 controls. OMICS 2013; 17: 200–214. 69. Gonullu G, Basturk B, Evrensel T, et al. Association of breast cancer and cytokine gene polymorphism in Turkish women. Saudi Med 2007; 28: 1728–1733. 70. Alamartine E, Berthoux P, Mariat C, et al. Interleukin-10 promoter polymorphisms and susceptibility to skin squamous cell carcinoma after renal transplantation. J Invest Dermatol 2003; 120: 99–103. 71. Yao JG, Gao LB, Liu YG, et al. Genetic variation in interleukin-10 gene and risk of oral cancer. Clin Chim Acta 2008; 388: 84–88. 72. Atoum MF. ACC interleukin-10 gene promoter haplotype as a breast cancer risk factor predictor among Jordanian females. Onco Targets Ther 2016; 9: 3353–3357. 73. Venetsanakos E, Beckman I, Bradley J, et al. High incidence of interleukin 10 mRNA but not interleukin 2 mRNA detected in human breast tumours. Br J Cancer 1997; 75: 1826–1830. 74. Nakagomi H, Pisa P, Pisa EK, et al. Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma. Int J Cancer 1995; 63: 366–371. 75. Pisa P, Halapi E, Pisa EK, et al. Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. Proc Natl Acad Sci U S A 1992; 89: 7708–7712. 76. Kruger-Krasagakes S, Krasagakis K, Garbe C, et al. Expression of interleukin 10 in human melanoma. Br J Cancer 1994; 70: 1182–1185. 77. Turner DM, Williams DM, Sankaran D, et al. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8. 78. Wu MS, Wu CY, Chen CJ, et al. Interleukin-10 genotypes associate with the risk of gastric carcinoma in Taiwanese Chinese. Int J Cancer 2003; 104: 617–623. 79. Wu MS, Huang SP, Chang YT, et al. Tumor necrosis factor-alpha and interleukin-10 promoter polymorphisms in Epstein-Barr virus-associated gastric carcinoma J Infect Dis 2002; 185: 106–109.https://doi.org/10.1177/1010428317713393https://t.ly/LXjxAMSA Google ScholarInterleukin-10 is involved in carcinogenesis by supporting tumor escape from the immune response. The aim of this study was to assess the single nucleotide polymorphisms, −1082A/G, −819T/C and −592A/C, in interleukin-10 gene promoter in inflammatory breast cancer compared to non–inflammatory breast cancer and association of these polymorphisms with interleukin-10 gene expression. We enrolled 105 breast cancer tissue (72 non–inflammatory breast cancer and 33 inflammatory breast cancer) patients and we determined the three studied single nucleotide polymorphisms in all samples by polymerase chain reaction restriction fragment length polymorphism and investigated their association with the disease and with various prognostic factors. In addition, we assessed the expression of interleukin-10 gene by realtime quantitative reverse transcription polymerase chain reaction and the correlation between studied single nucleotide polymorphisms and interleukin-10 messenger RNA expression. We found co-dominant effect as the best inheritance model (in the three studied single nucleotide polymorphisms in non–inflammatory breast cancer and inflammatory breast cancer samples), and we didn’t identify any association between single nucleotide polymorphisms genotypes and breast cancer prognostic factors. However, GCC haplotype was found highly associated with inflammatory breast cancer risk (p<0.001, odds ratio=43.05). Moreover, the expression of interleukin-10 messenger RNA was significantly higher (p<0.001) by 5.28-fold and 8.95-fold than non–inflammatory breast cancer and healthy control, respectively, where GCC haplotype significantly increased interleukin-10 gene expression (r=0.9, p<0.001).enUniversity of Interleukin-10, inflammatory breast cancer, haplotype, single nucleotide polymorphismArticlehttps://doi.org/10.1177/1010428317713393