Correlação entre o polimorfismo (-1082) da interleucina-10 e o desenvolvimento de carcinomas de pele

RESUMO

Objetivo: O câncer de pele é o mais frequente no Brasil especialmente em Santa Catarina. A interleucina-10 (IL-10) é uma citocina imunossupressora que pode possibilitar a fuga das células cancerosas do sistema imune, deste modo, polimorfismos no gene da IL-10 têm sido implicados na susceptibilidade e desenvolvimento de neoplasias. Este estudo teve como objetivo analisar as frequências alélicas e genotípicas do gene da IL-10 e sua associação com carcinomas de pele.

Métodos: Tratou-se de um estudo caso-controle onde foram analisadas 90 amostras, sendo o grupo teste composto por 49 tecidos de epiderme com carcinoma e o grupo controle por 41 raspados de mucosa oral de indivíduos sadios. A técnica ARMS-PCR foi utilizada para a identificação do polimorfismo.

Resultados: A frequência alélica para o grupo controle foi de 70% para o alelo A e 30% para o G; no grupo teste obteve-se 44% para o alelo A e 56% para o alelo G. A frequência genotípica observada no grupo controle foi AA (42%), AG (56%) e GG (25), e no grupo teste AA (24%), AG (39%) e GG (37%). Houve uma diferença estatística entre os grupos, tanto para a frequência alélica, quanto para o genótipo (p<0,05).

Conclusão: Observou-se uma maior prevalência do alelo G e dos genótipos AG e GG no grupo teste, quando comparado com o grupo controle, fator que poderia ser um adjuvante no desenvolvimento de carcinomas da epiderme. Este resultado demonstra a importância da resposta imune no desenvolvimento no processo de transformação de malignidade.

ABSTRACT

Objective: Skin cancer is the most common in Brazil especially in Santa Catarina. Inter-leukin-10 (IL-10) is an immunosuppressive cytokine that can allow the escape of cancer cells of the immune system, thereby polymorphisms in the IL-10 gene have been implicated in susceptibility and the development of malignancies. This study aimed to analyze the frequencies of the alleles and genotypic at position -1082 of the promoter region of IL-10 and its association with skin carcinomas.

Methods: This was a case-control study which analyzed 90 samples, and the test group of 49 skin tissue carcinoma and the control group by 41 scrapings oral mucosa of healthy individuals. The ARMS-PCR was used to identify the polymorphism.

Results: The allelic frequency for the control group was 70% for the A allele and 30% for G; in the test group gave 44% to 56% allele A and allele G Genotype frequency observed in the control group was AA (42%), AG (56%) and GG (25), while in group test was AA (24%), AG (39%) and GG (37%). There was a statistical difference between groups for both the allelic frequency, as for genotype (p <0.05).

Conclusion: There was a higher prevalence of the G allele and genotype AG and GG in the test group compared to the control group, a factor that could be an adjuvant in the development of skin carcinomas. This result demonstrates the importance of developing immune response in the malignant transformation process.

Descritores:

Imunossupressão - Interleucina-10 - Polimorfismo - Carcinoma epithelial

Keywords:

Immunosuppression - Interleukin-10 - Polymorphism - Epithelial carcinoma

• REFERÊNCIAS BIBLIOGRÁFICAS

• 1 Sociedade Brasileira de Dermatologia. Análise de dados das campanhas de prevenção ao câncer da pele promovidas pela Sociedade Brasileira de Dermatologia de 1999 a 2005. An Bras Dermatol 2006; 81 (06) 533-9
• 2 Instituto Nacional do Câncer (INCA). Pele não- melanoma [Internet]. Rio de Janeiro: INCA; 2013. [citado 2015 Nov 13]. Disponível em http://www2.inca.gov.br/wps/wcm/connect/tiposdecancer/site/home/pele_nao_melanoma 2015
• 3 Lallagherrp Lallagherrp, Lee TK. Adverse effects of ultraviolet radiation: a brief review. Prog Biophys Mol Biol 2006; 92 (01) 119-31
• 4 Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. editors Cancer incidence in five continents. Lyon (France): IARC; 2002
• 5 Duarte I, Santos A, Sousa H, Catarino R, Pinto D, Matos A. et al. G-308A TNF-alpha polymorphism is associated with an increased risk of invasive cervical cancer. Biochem Biophys Res Commun 2005; 334 (02) 588-92
• 6 Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against câncer: a counterpoint. J Leukoc Biol 2005; 78 (05) 1043-51
• 7 Mapara M, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol 2004; 22 (06) 1136-51
• 8 Zidi S, Gazouani E, Stayoussef M, Mezlini A, Ahmed SK, Ya-Coubi-Loueslati B. et al. IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians. Cytokine 2015; 76 (02) 343-7
• 9 Giannini SL, Hubert P, Doyen J, Boniver J, Delvenne P. Influence of the mucosal epithelium microenvironment on Langerhans cells: implications for the development of squamous intraepithelial lesions of the cervix. Int J Cancer 2002; 97 (05) 654-9
• 10 Moore TO, Moore AY, Carrasco D, Vander Straten M, Arany I, Au W, Tyring SK. Human papillomavirus, smoking, and cancer. J Cutan Med Surg 2001; 5 (04) 323-8
• 11 Sredni B, Weil M, Khomenok G, Lebenthal I, Teitz S, Mardor Y. et al. Ammonium trichloro(dioxoethylene-o,o’)tellu-rate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop. Cancer Res 2004; 64 (05) 1843-52
• 12 Mocellin S, Wang E, Panelli M, Pilati P, Marincola FM. DNA array-based gene profiling in tumor immunology. Clin Cancer Res 2004; Jul 15 10 (14) 4597-606
• 13 Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; Feb 24 (01) 1-8
• 14 Medrano JF, Aasen E, Sharrow L. DNA extraction from nucleated red blood cells. Biotechniques 1990; 8 (01) 43 Review
• 15 Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol 1999; 7 (02) 127-8
• 16 Sesarini C, Giménez ML, Redal MA, Izbizky G, Aiello H, Argibay P, Otaño L. Diagnóstico genético prenatal no invasivo de factor Rh y sexo fetal a través delanálisis de ADN fetal libre en plasma materno. Arch Argent Pediatr (Buenos Aires) 2009; 107 (05) 405-9
• 17 Fernandes AP, Gonçalves MA, Duarte G, Cunha FQ, Simões RT, Donadi EA. HPV16, HPV18, and HIV infection may influence cervical cytokine intra lesional levels. Virology 2005; 334 (02) 294-8
• 18 Song SH, Lee JK, Seok OS, Saw HS. The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV viral load in the uterine cervix. Gynecol Oncol 2007; 104 (03) 732-8
• 19 Sharma A, Rajappa M, Saxena A, Sharma M. Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix. Int J Gynecol Cancer 2007; 17 (04) 879-85
• 20 Howell WM, Rose-Zerilli MJ. Cytokine gene polymorphisms, cancer susceptibility, and prognosis. J Nutrition 2007 137 194-9
• 21 Alamartine E, Berthoux P, Mariat C, Cambazard F, Berthoux F. Interleukin-10 promoter polymorphisms and susceptibility to skin squamous cell carcinoma after renal transplantation. J Invest Dermatol 2003; 120 (01) 99-103
• 22 Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, Green AC, Bavinck JN, Perry A, Spencer S, Rees JR, Mott LA, Pawlita M. Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 2006; 98 (06) 389-95
• 23 Gao X, Chen J, Tong Z, Yang G, Yao Y, Xu F, Zhou J. In-terleukin-10 promoter gene polymorphisms and susceptibility to tuberculosis: a meta-analysis. PLoS One 2015; 10 (06) e0127496
• 24 Kim J, Modlin RL, Moy RL, Dubinett SM, McHugh T, Nicko-Loff BJ, Uyemura K. IL-10 production in cutaneous basal and squamous cell carcinomas. A mechanism for evading the local T cell immune response. J Immunol 1995; Aug 15 155 (04) 2240-7
• 25 Matsumoto K, Oki A, Satoh T, Okada S, Minaguchi T, Onuki M, Ochi H, Nakao S, Sakurai M. et al. Interleukin-10 -1082 gene polymorphism and susceptibility to cervical cancer among Japanese women. Jpn J Clin Oncol 2010; 40 (11) 1113-6
• 26 Korobeinikova E, Myrzaliyeva D, Ugenskiene R, Raulinaityte D, Gedminaite J, Smigelskas K, Juozaityte E. The prognostic value of IL10 and TNF alpha functional polymorphisms in premenopausal early-stage breast cancer patients. BMC Genet 2015; 16: 70
• 27 Lech-Maranda E, Baseggio L, Bienvenu J, Charlot C, Berger F, Rigal D, Warzocha K, Coiffier B, Salles G. Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. Blood 2004; May 1 103 (09) 3529-34
• 28 Kirkpatrick A, Bidwell J, van den Brule AJ, Meijer CJ, Pawade J, Glew S. TNFalpha polymorphism frequencies in HPV-associated cervical dysplasia. Gynecol Oncol 2004; 92 (02) 675-9
• 29 Hollegaard MV, Bidwell JL. Cytokine gene polymorphism in human disease: on-line databases, Supplement 3. Genes Immun 2006; 7 (04) 269-76
• 30 McCarron SL, Edwards S, Evans PR, Gibbs R, Dearnaley DP, Dowe A. et al. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 2002 62 369-72
• 31 Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24 (01) 1-8