Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico
Gastric cancer (GC) is the second most common malignancy among men and the third in women, and therefore, an important public health problem in northern Brazil. The investigation of genetic factors related to immunological characteristics can aid the understanding of carcinogenesis in CG. The object...
| Autor principal: | OLIVEIRA, Gabriela Almeida de |
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| Grau: | Dissertação |
| Idioma: | por |
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Universidade Federal do Pará
2017
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http://repositorio.ufpa.br/jspui/handle/2011/7251 |
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ir-2011-72512017-12-14T16:13:51Z Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico OLIVEIRA, Gabriela Almeida de SANTOS, Ândrea Kely Campos Ribeiro dos http://lattes.cnpq.br/3899534338451625 Neoplasias gástricas Polimorfismo genético Citocinas Câncer gástrico Neoplasias gástricas Aparelho digestivo CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA Gastric cancer (GC) is the second most common malignancy among men and the third in women, and therefore, an important public health problem in northern Brazil. The investigation of genetic factors related to immunological characteristics can aid the understanding of carcinogenesis in CG. The objective of the present work was investigate polymorphisms present in interleukin genes IL17G-197A, IL 17FA7488G, TNFαG-308A, IL10G-1082A, IL10C-819T e IL10C-592A, on samples of patients with gastric cancer and healthy patients without cancer. Case group was composed of 100 patients diagnosed with CG, met in the Hospital HUJBB (Pará, Brazil). Control group was composed of 100 individuals without cancer, unrelated, of the same population. The genetic material was extracted from 5 mL of peripheral blood with the DNA commercial kit from Roche, followed by quantification with the NanoDrop 1000 spectrophotometer. Analysis of the molecular polymorphisms was performed by real-time PCR with Taqman® probes. Measures of ancestry were investigated using a panel of 48 autosomal ancestry informative markers (AIMs). The proportions of ancestry of European, African and Amerindian were estimated using the software STRUCTURE v. 2.3.3. It was observed that the ethnic composition of the case group was 27% African, 42% European and 31% of Amerindian, while in the control group 21% African, 52% of European and 27% of Amerindian. In relation to the set of markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A), when the genotypic and haplotypic patterns were compared, it was noted that the haplotype distribution related to high expression (GCC/GCC, GCA, GCC/GCC/GTC, GCA/GCA, GCA/GTA) was more frequent in the patients with gastric cancer (P = 1,15e-11; OR = 2.630; IC 95% = 2.116-3.271). Among the individuals with the genotype related to the high production of IL-10, it was observed that the control group had more European contribution in their ancestry (P = 1e-06) while the group of patients with CG had more African contribution in their ancestry (P = 1.4e-5). Patients who presented TNF-α AA and TNF-α AG genotypes for TNF-α gene mutation presented a higher risk for development of cancer (P<0.001; OR 10.375; IC 95% 3.149-34.061). It is concluded that patients with a distribution of haplotypic markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A) related to a higher expression and higher contribution of African ancestry have a high risk of developing gastric cancer. FADESP - Fundação de Amparo e Desenvolvimento da Pesquisa No Norte do Brasil, o câncer gástrico (GC) é a segunda neoplasia mais frequente entre os homens e o terceiro nas mulheres, portanto, um importante problema de saúde pública. A investigação de fatores genéticos relacionados com características imunológicas pode auxiliar o entendimento da carcinogênese no CG. O objetivo do presente trabalho foi polimorfismos presentes nos genes das interleucinas IL17G-197A, IL 17FA7488G, TNFαG-308A, IL10G- 1082A, IL10C-819T e IL10C-592A, em amostras de pacientes com câncer gástrico e sem câncer. O grupo caso foi composto por 100 pacientes diagnosticados com CG, atendidos no Hospital HUJBB (Pará, Brasil). O grupo controle foi constituído de 100 indivíduos, não aparentados, sem câncer da mesma população. O material genético foi extraído a partir de 5 mL de sangue periférico pelo kit comercial de DNA da Roche, seguido de quantificação com o NanoDrop 1000 spectrophotometer. Molecular analysis of the polymorphisms was performed by real-time PCR with TaqMan® probes. E as medidas de ancestralidade foram investigadas utilizando um painel de 48 marcadores autossômicos informativos de ancestralidade (AIMs). As proporções de ancestralidade de Europeu, Africano e Ameríndio foram estimadas usando o software STRUCTURE v.2.3.3. Como resultado, observou-se que a composição étnica do grupo com câncer foi de 27% africano, 42% europeu, e 31% de ameríndia. No grupo sem câncer, a composição foi de 21 % africano, 52% europeia, e 27% de ameríndia. Em relação ao conjunto de marcadores da interleucina IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A), quando comparados os padrões genotípicos e haplotípicos observou-se que a distribuição haplotípica, quando relacionada a elevada expressão (GCC/GCC, GCC/GCA, GCC/GTC, GCA/GCA, GCA/GTA) foi mais frequente no grupo de pacientes com câncer gástrico (p=1,15E-11; OR=2,630; IC 95%=2,116-3,271). Em indivíduos que possuíam o genótipo relacionado com a elevada produção de IL-10, detectou-se maior frequência da ancestralidade europeia no grupo de indivíduos controle (p=1E-06), enquanto no grupo de pacientes com CG observou significante frequência da ancestralidade africana (p=1.4 e-5), pacientes que apresentaram genótipos TNF-α AA e TNF-α AG para mutação no gene TNF-α, apresentam risco elevado para desenvolvimento do câncer (P <000.1; OR 10.375; IC 95% 3.149- 34.061). Concluimos que a distribuição haplotípica dos marcadores da interleucina IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A) quando relacionados a elevada expressão e predominância de ancestralidade africana, possuem maior risco de desenvolvimento do CG. 2017-01-09T17:13:32Z 2017-01-09T17:13:32Z 2016-02-02 Dissertação OLIVEIRA, Gabriela Almeida de. Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico. 2016. 73 f. Dissertação (Mestrado). Universidade Federal do Pará, Núcleo de Pesquisas em Oncologia, 2016, Belém, 2005. Programa de Pós-Graduação em Oncologia e Ciências Médicas. http://repositorio.ufpa.br/jspui/handle/2011/7251 por Acesso Aberto application/pdf Universidade Federal do Pará Brasil Núcleo de Pesquisas em Oncologia UFPA Programa de Pós-Graduação em Oncologia e Ciências Médicas |
| institution |
Repositório Institucional - Universidade Federal do Pará |
| collection |
RI-UFPA |
| language |
por |
| topic |
Neoplasias gástricas Polimorfismo genético Citocinas Câncer gástrico Neoplasias gástricas Aparelho digestivo CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA |
| spellingShingle |
Neoplasias gástricas Polimorfismo genético Citocinas Câncer gástrico Neoplasias gástricas Aparelho digestivo CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA OLIVEIRA, Gabriela Almeida de Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| topic_facet |
Neoplasias gástricas Polimorfismo genético Citocinas Câncer gástrico Neoplasias gástricas Aparelho digestivo CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CANCEROLOGIA |
| description |
Gastric cancer (GC) is the second most common malignancy among men and the third in women, and therefore, an important public health problem in northern Brazil. The investigation of genetic factors related to immunological characteristics can aid the understanding of carcinogenesis in CG. The objective of the present work was investigate polymorphisms present in interleukin genes IL17G-197A, IL 17FA7488G, TNFαG-308A, IL10G-1082A, IL10C-819T e IL10C-592A, on samples of patients with gastric cancer and healthy patients without cancer. Case group was composed of 100 patients diagnosed with CG, met in the Hospital HUJBB (Pará, Brazil). Control group was composed of 100 individuals without cancer, unrelated, of the same population. The genetic material was extracted from 5 mL of peripheral blood with the DNA commercial kit from Roche, followed by quantification with the NanoDrop 1000 spectrophotometer. Analysis of the molecular polymorphisms was performed by real-time PCR with Taqman® probes. Measures of ancestry were investigated using a panel of 48 autosomal ancestry informative markers (AIMs). The proportions of ancestry of European, African and Amerindian were estimated using the software STRUCTURE v. 2.3.3. It was observed that the ethnic composition of the case group was 27% African, 42% European and 31% of Amerindian, while in the control group 21% African, 52% of European and 27% of Amerindian. In relation to the set of markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A), when the genotypic and haplotypic patterns were compared, it was noted that the haplotype distribution related to high expression (GCC/GCC, GCA, GCC/GCC/GTC, GCA/GCA, GCA/GTA) was more frequent in the patients with gastric cancer (P = 1,15e-11; OR = 2.630; IC 95% = 2.116-3.271). Among the individuals with the genotype related to the high production of IL-10, it was observed that the control group had more European contribution in their ancestry (P = 1e-06) while the group of patients with CG had more African contribution in their ancestry (P = 1.4e-5). Patients who presented TNF-α AA and TNF-α AG genotypes for TNF-α gene mutation presented a higher risk for development of cancer (P<0.001; OR 10.375; IC 95% 3.149-34.061). It is concluded that patients with a distribution of haplotypic markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A) related to a higher expression and higher contribution of African ancestry have a high risk of developing gastric cancer. |
| author_additional |
SANTOS, Ândrea Kely Campos Ribeiro dos |
| author_additionalStr |
SANTOS, Ândrea Kely Campos Ribeiro dos |
| format |
Dissertação |
| author |
OLIVEIRA, Gabriela Almeida de |
| title |
Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| title_short |
Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| title_full |
Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| title_fullStr |
Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| title_full_unstemmed |
Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico |
| title_sort |
polimorfismos de citocinas (tnf-a, il-10 e il-17) no câncer gástrico |
| publisher |
Universidade Federal do Pará |
| publishDate |
2017 |
| url |
http://repositorio.ufpa.br/jspui/handle/2011/7251 |
| _version_ |
1787147688043610112 |
| score |
11.675088 |