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Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer

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Pathology & Oncology Research

Abstract

We studied the contribution of the IL12A 3′UTR G>A (rs568408) and IL12B 3′UTR A>C (rs3212227) polymorphisms to the risk of cervical cancer. These polymorphisms were genotyped in four hundred-five patients with cervical cancer and four hundred fifty unrelated healthy females from the Polish population. Logistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status revealed that the IL12B 3′UTR A>C polymorphism could be a genetic risk factor for cervical cancer. The adjusted odds ratio (OR) for patients with the A/C genotype vs A/A genotype was 1.557 (95 % CI = 1.173–2.066, p = 0.0178) and adjusted OR for the C/C or A/C genotype vs the A/A genotype was 1.635 (95 % CI = 1.241–2.153, p = 0.0125). However, logistic regression analysis did not show an association of the IL12A 3′UTR G>A polymorphism with cervical cancer development in the studied Polish population. Our studies confirmed that the IL12B 3′UTR A>C polymorphism may be a genetic risk factor for cervical cancer.

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References

  1. Arbyn M, Raifu AO, Autier P et al (2007) Burden of cervical cancer in Europe: estimates for 2004. Ann Oncol 18:1708–1715

    Article  PubMed  CAS  Google Scholar 

  2. Muñoz N, Bosch FX, de Sanjosé S et al (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348:518–527

    Article  PubMed  Google Scholar 

  3. Walboomers JM, Jacobs MV, Manos MM et al (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189:12–19

    Article  PubMed  CAS  Google Scholar 

  4. Giuliano AR, Harris R, Sedjo RL et al (2002) Incidence, prevalence, and clearance of type-specific human papillomavirus infections: the Young Women’s Health Study. J Infect Dis 186:462–469

    Article  PubMed  Google Scholar 

  5. Magnusson PK, Lichtenstein P, Gyllensten UB (2000) Heritability of cervical tumours. Int J Cancer 88:698–701

    Article  PubMed  CAS  Google Scholar 

  6. Hemminki K, Chen B (2006) Familial risks for cervical tumors in full and half siblings: etiologic apportioning. Cancer Epidemiol Biomarkers Prev 15:1413–1414

    Article  PubMed  Google Scholar 

  7. Castellsague X, Munoz N (2003) Chapter 3: cofactors in human papillomavirus carcinogenesis–role of parity, oral contraceptives, and tobacco smoking. J Natl Cancer Inst Monogr 20–28

  8. Moreno V, Bosch FX, Munoz N et al (2002) Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case–control study. Lancet 359:1085–1092

    Article  PubMed  CAS  Google Scholar 

  9. Wu TC, Kurman RJ (1997) Analysis of cytokine profiles in patients with human papillomavirus-associated neoplasms. J Natl Cancer Inst 89:185–187

    Article  PubMed  CAS  Google Scholar 

  10. Scott M, Stites DP, Moscicki AB (1999) Th1 cytokine patterns in cervical human papillomavirus infection. Clin Diagn Lab Immunol 6:751–755

    PubMed  CAS  Google Scholar 

  11. Trinchieri G (1998) Interleukin-12: a cytokine at the interface of inflammmation and immunity. Adv Immunol 70:83–243

    Article  PubMed  CAS  Google Scholar 

  12. Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146

    Article  PubMed  CAS  Google Scholar 

  13. Macatonia SE, Hosken NA, Litton M et al (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154:5071–5079

    PubMed  CAS  Google Scholar 

  14. D’Andrea A, Rengaraju M, Valiante NM et al (1992) Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med 176:1387–1398

    Article  PubMed  Google Scholar 

  15. Cassatella MA, Meda L, Gasperini S et al (1995) Interleukin-12 production by human polymorphonuclear leukocytes. Eur J Immunol 25:1–5

    Article  PubMed  CAS  Google Scholar 

  16. Colombo MP, Trinchieri G (2002) Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 13:155–168

    Article  PubMed  CAS  Google Scholar 

  17. Brunda MJ, Luistro L, Warrier RR et al (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178:1223–1230

    Article  PubMed  CAS  Google Scholar 

  18. Imagawa Y, Satake K, Kato Y et al (2004) Antitumor and antiangiogenic effects of interleukin 12 gene therapy in murine head and neck carcinoma model. Auris Nasus Larynx 31:239–245

    Article  PubMed  Google Scholar 

  19. Sieburth D, Jabs EW, Warrington JA et al (1992) Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. Genomics 14:59–62

    Article  PubMed  CAS  Google Scholar 

  20. Lan Q, Zheng T, Rothman N et al (2006) Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma. Blood 107:4101–4108

    Article  PubMed  CAS  Google Scholar 

  21. Purdue MP, Lan Q, Kricker A et al (2007) Polymorphisms in immune function genes and risk of non-Hodgkin lymphoma: findings from the New South Wales non-Hodgkin lymphoma study. Carcinogenesis 28:704–712

    Article  PubMed  CAS  Google Scholar 

  22. Nieters A, Yuan JM, Sun CL et al (2005) Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association. Cancer 103:740–748

    Article  PubMed  CAS  Google Scholar 

  23. Lee KM, Shen M, Chapman RS et al (2007) Polymorphisms in immunoregulatory genes, smoky coal exposure and lung cancer risk in Xuan Wei, China. Carcinogenesis 28:1437–1441

    Article  PubMed  CAS  Google Scholar 

  24. Hou L, El-Omar EM, Chen J et al (2007) Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer. Carcinogenesis 28:118–123

    Article  PubMed  CAS  Google Scholar 

  25. Navaglia F, Basso D, Zambon CF et al (2005) Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals. J Med Genet 42:503–510

    Article  PubMed  CAS  Google Scholar 

  26. Brown EE, Fallin D, Ruczinski I et al (2006) Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity. Cancer Epidemiol Biomark Prev 15:926–934

    Article  CAS  Google Scholar 

  27. Howell WM, Turner SJ, Theaker JM et al (2003) Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma. Eur J Immunogenet 30:409–414

    Article  PubMed  CAS  Google Scholar 

  28. Landi S, Gemignani F, Bottari F et al (2006) Polymorphisms within inflammatory genes and colorectal cancer. J Negat Results Biomed 5:15

    Article  PubMed  Google Scholar 

  29. Ben Chaaben A, Busson M, Douik H et al (2011) Association of IL-12p40 +1188 A/C polymorphism with nasopharyngeal cancer risk and tumor extension. Tissue Antigens 78:148–151

    Article  PubMed  CAS  Google Scholar 

  30. Chen X, Han S, Wang S et al (2009) Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res 15:400–405

    Article  PubMed  CAS  Google Scholar 

  31. Kordi Tamandani DM, Shekari M, Suri V et al (2009) Interleukin-12 gene polymorphism and cervical cancer risk. Am J Clin Oncol

  32. Han SS, Cho EY, Lee TS et al (2008) Interleukin-12 p40 gene (IL12B) polymorphisms and the risk of cervical caner in Korean women. Eur J Obstet Gynecol Reprod Biol 140:71–75

    Article  PubMed  CAS  Google Scholar 

  33. Noguchi Y, Jungbluth A, Richards EC et al (1996) Effect of interleukin 12 on tumor induction by 3-methylcholanthrene. Proc Natl Acad Sci USA 93:11798–11801

    Article  PubMed  CAS  Google Scholar 

  34. Nanni P, Nicoletti G, De Giovanni C et al (2001) Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J Exp Med 194:1195–1205

    Article  PubMed  CAS  Google Scholar 

  35. Bais AG, Beckmann I, Ewing PC et al (2007) Cytokine release in HR-HPV(+) women without and with cervical dysplasia (CIN II and III) or carcinoma, compared with HR-HPV(−) controls. Mediators Inflamm 24147

  36. Kadish AS, Timmins P, Wang Y et al (2002) Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide. Cancer Epidemiol Biomark Prev 11:483–488

    CAS  Google Scholar 

  37. Jin HS, Park EK, Lee JM et al (2005) Immunization with adenoviral vectors carrying recombinant IL-12 and E7 enhanced the antitumor immunity to human papillomavirus 16-associated tumor. Gynecol Oncol 97:559–567

    Article  PubMed  CAS  Google Scholar 

  38. Indrová M, Bieblová J, Rossowska J et al (2009) HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy. Int J Oncol 34:173–179

    PubMed  Google Scholar 

  39. Mikyšková R, Indrová M, Símová J et al (2011) Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine. Oncol Rep 25:1683–1689

    PubMed  Google Scholar 

  40. Chen T, Liang W, Gao L et al (2011) Association of single nucleotide polymorphisms in interleukin 12 (IL-12A and -B) with asthma in a Chinese population. Hum Immunol 72:603–606

    Article  PubMed  CAS  Google Scholar 

  41. Morris GA, Edwards DR, Hill PC et al (2011) Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina. PLoS One 6:e16656

    Article  PubMed  CAS  Google Scholar 

  42. Morahan G, McKinnon E, Berry J et al (2009) Type I diabetes genetics consortium. Evaluation of IL12B as a candidate type I diabetes susceptibility gene using data from the type I diabetes genetics consortium. Genes Immun 10(Suppl 1):S64–S68

    Article  PubMed  CAS  Google Scholar 

  43. Nair RP, Stuart PE, Kullavanijaya P et al (2010) Genetic evidence for involvement of the IL23 pathway in Thai psoriatics. Arch Dermatol Res 302:139–143

    Article  PubMed  CAS  Google Scholar 

  44. Filer C, Ho P, Smith RL et al (2008) Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum 58:3705–3709

    Article  PubMed  CAS  Google Scholar 

  45. Phawong C, Ouma C, Tangteerawatana P et al (2010) Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults. Immunogenetics 62:345–356

    Article  PubMed  CAS  Google Scholar 

  46. Cerhan JR, Wang S, Maurer MJ et al (2007) Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. Blood 109:5439–5446

    Article  PubMed  CAS  Google Scholar 

  47. Morahan G, Huang D, Ymer SI et al (2001) Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 27:218–221

    Article  PubMed  CAS  Google Scholar 

  48. Davoodi-Semiromi A, Yang JJ, She JX (2002) IL-12p40 is associated with type 1 diabetes in Caucasian-American families. Diabetes 51:2334–2336

    Article  PubMed  CAS  Google Scholar 

  49. Seegers D, Zwiers A, Strober W et al (2002) A TaqI polymorphism in the 3′UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun 3:419–423

    Article  PubMed  CAS  Google Scholar 

  50. Yilmaz V, Yentür SP, Saruhan-Direskeneli G (2005) IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 30:188–194

    Article  PubMed  CAS  Google Scholar 

  51. Guo T, Yang S, Liu N et al (2011) Association study of interleukin-12A gene polymorphisms with Graves’ disease in two Chinese populations. Clin Endocrinol (Oxf) 74:125–129

    Article  CAS  Google Scholar 

  52. Chen Y, Zheng T, Lan Q et al (2011) Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma. Blood 117:585–590

    Article  PubMed  CAS  Google Scholar 

  53. Liu L, Xu Y, Liu Z et al (2011) IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 128:1692–1696

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Supported by grant No 502-01-01124182-07474, Poznan University of Medical Sciences. The technical assistance of Ms. Monika Świerczewska is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Centre Poznan, Poznań, Poland

    Andrzej Roszak

  2. Department of Biochemistry and Molecular Biology, University of Medical Sciences, 6 Święcickiego St, 60-781, Poznań, Poland

    Adrianna Mostowska, Margarita Lianeri & Pawel P. Jagodziński

  3. Department of Computer Science and Statistics, Poznan University of Medical Sciences Poznan, Poznań, Poland

    Anna Sowińska

  4. Department of Electroradiology, Poznan University of Medical Sciences, Poznań, Poland

    Andrzej Roszak

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  1. Andrzej Roszak
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Correspondence to Pawel P. Jagodziński.

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Roszak, A., Mostowska, A., Sowińska, A. et al. Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer. Pathol. Oncol. Res. 18, 997–1002 (2012). https://doi.org/10.1007/s12253-012-9532-x

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  • DOI: https://doi.org/10.1007/s12253-012-9532-x

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