Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Coêlho, Marina de Castro
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraíba
Brasil
Odontologia
Programa de Pós-Graduação em Odontologia
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/22797
Resumo: Oral mucositis (OM) is a painful inflammatory oral condition caused by chemotherapy in children, with great variability when it comes to how this adverse effect occurs in this population. Oxidative stress is known as a mediator of OM and pro-inflammatory cytokines contribute in the amplification of the immune response, worsening the patient’s oral condition. This study aimed to investigate the frequency of polymorphisms rs4880 (SOD2 47 C/T), rs7943316 (CAT -21 A/T), rs1800629 (TNF-α -308 G/A) and rs1800795 (IL-6 -174 G/C) and their possible associations with chemo-induced OM occurrence and severity in oncopediatric patients. This was an observational, cross-sectional research. Oral epithelial samples from 95 children or adolescents with leukemia or lymphoma submitted to chemotherapy were collected and the genomic DNA was extracted. Singlenucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) and fragments were observed in 6% polyacrilamide gels stained with silver nitrate. Demographic data and information concerning occurrence of OM were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was limited to the first 60 days of treatment and obtained from appropriately filled OAG registers, in which the score 1 represents absence of oral alterations, score 2 refers to mild to moderate oral alterations, and score 3 corresponds to severe oral mucositis (SOM). Descriptive and inferential statistics were performed with Student’s T test, Chi-squared and Fisher’s Exact tests, with p<0.05. The mean age for the entire sample was 10 yo, and the majority was comprised by male individuals (57.89%). The female sex was considered a protective factor for OM occurrence (RR=0.78; CI [0.64;0.96]) The most common cancer type was acute lymphoblastic leukemia (74.73%). No associations between the SNPs and OM occurrence were detected. For the OM severity analysis, the AA genotype for CAT was more frequent amongst SOM individuals (p=0.04, RR = 1.82; CI = [1.13;2.91]) while the GA genotype for TNF-α was the most frequent amongst individuals without SOM (p=0.03). For SOD and IL-6, the most frequent genotypes were CT and GG respectively for all groups (p>0.05). In conclusion, the AA genotype for rs7943316 could influence OM severity. Due to the impossibility of generating a confidence interval to support the observed associations, data on rs1800629 are inconclusive. OM severity studies with larger sample sizes are encouraged. Genotype combination analysis are still to be carried out. Genetic studies aim unravel the patient’s molecular profile, allowing the development of efficient predictive models and the elaboration of accurate treatment plans.
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spelling Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzidaMucosite oralPolimorfismos genéticosEstresse oxidativoCitocinasOral mucositisGenetic polymorphismsOxidative stressCytokinesCNPQ::CIENCIAS DA SAUDE::ODONTOLOGIAOral mucositis (OM) is a painful inflammatory oral condition caused by chemotherapy in children, with great variability when it comes to how this adverse effect occurs in this population. Oxidative stress is known as a mediator of OM and pro-inflammatory cytokines contribute in the amplification of the immune response, worsening the patient’s oral condition. This study aimed to investigate the frequency of polymorphisms rs4880 (SOD2 47 C/T), rs7943316 (CAT -21 A/T), rs1800629 (TNF-α -308 G/A) and rs1800795 (IL-6 -174 G/C) and their possible associations with chemo-induced OM occurrence and severity in oncopediatric patients. This was an observational, cross-sectional research. Oral epithelial samples from 95 children or adolescents with leukemia or lymphoma submitted to chemotherapy were collected and the genomic DNA was extracted. Singlenucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) and fragments were observed in 6% polyacrilamide gels stained with silver nitrate. Demographic data and information concerning occurrence of OM were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was limited to the first 60 days of treatment and obtained from appropriately filled OAG registers, in which the score 1 represents absence of oral alterations, score 2 refers to mild to moderate oral alterations, and score 3 corresponds to severe oral mucositis (SOM). Descriptive and inferential statistics were performed with Student’s T test, Chi-squared and Fisher’s Exact tests, with p<0.05. The mean age for the entire sample was 10 yo, and the majority was comprised by male individuals (57.89%). The female sex was considered a protective factor for OM occurrence (RR=0.78; CI [0.64;0.96]) The most common cancer type was acute lymphoblastic leukemia (74.73%). No associations between the SNPs and OM occurrence were detected. For the OM severity analysis, the AA genotype for CAT was more frequent amongst SOM individuals (p=0.04, RR = 1.82; CI = [1.13;2.91]) while the GA genotype for TNF-α was the most frequent amongst individuals without SOM (p=0.03). For SOD and IL-6, the most frequent genotypes were CT and GG respectively for all groups (p>0.05). In conclusion, the AA genotype for rs7943316 could influence OM severity. Due to the impossibility of generating a confidence interval to support the observed associations, data on rs1800629 are inconclusive. OM severity studies with larger sample sizes are encouraged. Genotype combination analysis are still to be carried out. Genetic studies aim unravel the patient’s molecular profile, allowing the development of efficient predictive models and the elaboration of accurate treatment plans.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqA mucosite oral (MO) é uma condição oral inflamatória e dolorosa decorrente do tratamento do câncer, porém há grande variabilidade na forma de manifestação deste efeito adverso nesta população. O estresse oxidativo é reconhecidamente um mediador da MO e citocinas pró-inflamatórias participam na amplificação da resposta imune, agravando a condição bucal do paciente. O objetivo do presente estudo foi investigar os polimorfismos rs4880 (SOD2 47 C/T), rs7943316 (CAT -21 A/T), rs1800629 (TNF-α - 308 G/A) e rs1800795 (IL-6 -174 G/C) e possíveis associações com ocorrência e severidade de MO quimioinduzida em pacientes oncopediátricos. Realizou-se uma pesquisa observacional transversal. Amostras de epitélio bucal de 95 crianças ou adolescentes com leucemias ou linfomas que passaram por tratamento quimioterápico foram coletadas e o DNA genômico foi extraído. Os polimorfismos foram detectados por PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) e os resultados observados em gel de poliacrilamida 6%, corado com nitrato de prata. Dados demográficos e informações sobre ocorrência da MO foram obtidos de prontuários da equipe odontológica. Informações sobre severidade foram limitadas aos primeiros 60 dias de tratamento e obtidas a partir de registros completos de OAG, onde o grau 1 indica ausência de alteração bucal, o grau 2 indica alterações leves/moderadas e o grau 3 indica mucosite oral grave (MOG). Foi realizada estatística descritiva e inferencial, utilizando os testes T Student, Qui-quadrado e Exato de Fisher, com p≤0,05. A média de idade para a amostra foi de 10 anos, com predomínio do sexo masculino (57,89%), e o tipo de câncer mais comum foi a leucemia linfoblástica aguda (74,73%). O sexo feminino foi considerado fator de proteção para ocorrência de MO (RR=0,78; IC [0,64;0,96]). Não foi detectada associação entre os polimorfismos e a ocorrência de MO. Para a análise de severidade, o genótipo AA para o gene CAT foi mais frequente em indivíduos com MOG (p=0.04, RR = 1,82; CI = [1,13;2,91]), e o genótipo GA para o gene TNF-α foi mais frequente em indivíduos sem MOG (p=0.03), não sendo possível gerar uma medida de efeito para a associação. Para os genes SOD2 e IL-6 os genótipos mais frequentes foram CT e GG respectivamente em todos os grupos (p>0.05). Conclui-se que o genótipo AA de rs7943316 pode contribuir com a severidade da mucosite. Os resultados para rs1800629 são inconclusivos, sendo necessários estudos de severidade da MO com tamanhos amostrais maiores para confirmar as associações observadas. Estudos genéticos visam traçar o perfil molecular do paciente, permitindo a criação de modelos preditivos efetivos e elaboração de plano de tratamento personalizado.Universidade Federal da ParaíbaBrasilOdontologiaPrograma de Pós-Graduação em OdontologiaUFPBOliveira, Naila Francis Paulo dehttp://lattes.cnpq.br/5659529393550374Coêlho, Marina de Castro2022-05-11T13:57:52Z2021-08-252022-05-11T13:57:52Z2021-08-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/22797porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-08-09T14:43:34Zoai:repositorio.ufpb.br:123456789/22797Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| bdtd@biblioteca.ufpb.bropendoar:2022-08-09T14:43:34Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
title Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
spellingShingle Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
Coêlho, Marina de Castro
Mucosite oral
Polimorfismos genéticos
Estresse oxidativo
Citocinas
Oral mucositis
Genetic polymorphisms
Oxidative stress
Cytokines
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
title_short Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
title_full Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
title_fullStr Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
title_full_unstemmed Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
title_sort Análise de polimorfismos nos genes SOD2, CAT, TNF-alfa e IL-6 em pacientes oncopediátricos com mucosite oral quimioinduzida
author Coêlho, Marina de Castro
author_facet Coêlho, Marina de Castro
author_role author
dc.contributor.none.fl_str_mv Oliveira, Naila Francis Paulo de
http://lattes.cnpq.br/5659529393550374
dc.contributor.author.fl_str_mv Coêlho, Marina de Castro
dc.subject.por.fl_str_mv Mucosite oral
Polimorfismos genéticos
Estresse oxidativo
Citocinas
Oral mucositis
Genetic polymorphisms
Oxidative stress
Cytokines
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
topic Mucosite oral
Polimorfismos genéticos
Estresse oxidativo
Citocinas
Oral mucositis
Genetic polymorphisms
Oxidative stress
Cytokines
CNPQ::CIENCIAS DA SAUDE::ODONTOLOGIA
description Oral mucositis (OM) is a painful inflammatory oral condition caused by chemotherapy in children, with great variability when it comes to how this adverse effect occurs in this population. Oxidative stress is known as a mediator of OM and pro-inflammatory cytokines contribute in the amplification of the immune response, worsening the patient’s oral condition. This study aimed to investigate the frequency of polymorphisms rs4880 (SOD2 47 C/T), rs7943316 (CAT -21 A/T), rs1800629 (TNF-α -308 G/A) and rs1800795 (IL-6 -174 G/C) and their possible associations with chemo-induced OM occurrence and severity in oncopediatric patients. This was an observational, cross-sectional research. Oral epithelial samples from 95 children or adolescents with leukemia or lymphoma submitted to chemotherapy were collected and the genomic DNA was extracted. Singlenucleotide polymorphisms (SNPs) were assessed with PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) and fragments were observed in 6% polyacrilamide gels stained with silver nitrate. Demographic data and information concerning occurrence of OM were obtained from dental charts of the multidisciplinary oral care team. Information on OM severity was limited to the first 60 days of treatment and obtained from appropriately filled OAG registers, in which the score 1 represents absence of oral alterations, score 2 refers to mild to moderate oral alterations, and score 3 corresponds to severe oral mucositis (SOM). Descriptive and inferential statistics were performed with Student’s T test, Chi-squared and Fisher’s Exact tests, with p<0.05. The mean age for the entire sample was 10 yo, and the majority was comprised by male individuals (57.89%). The female sex was considered a protective factor for OM occurrence (RR=0.78; CI [0.64;0.96]) The most common cancer type was acute lymphoblastic leukemia (74.73%). No associations between the SNPs and OM occurrence were detected. For the OM severity analysis, the AA genotype for CAT was more frequent amongst SOM individuals (p=0.04, RR = 1.82; CI = [1.13;2.91]) while the GA genotype for TNF-α was the most frequent amongst individuals without SOM (p=0.03). For SOD and IL-6, the most frequent genotypes were CT and GG respectively for all groups (p>0.05). In conclusion, the AA genotype for rs7943316 could influence OM severity. Due to the impossibility of generating a confidence interval to support the observed associations, data on rs1800629 are inconclusive. OM severity studies with larger sample sizes are encouraged. Genotype combination analysis are still to be carried out. Genetic studies aim unravel the patient’s molecular profile, allowing the development of efficient predictive models and the elaboration of accurate treatment plans.
publishDate 2021
dc.date.none.fl_str_mv 2021-08-25
2021-08-13
2022-05-11T13:57:52Z
2022-05-11T13:57:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/22797
url https://repositorio.ufpb.br/jspui/handle/123456789/22797
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Odontologia
Programa de Pós-Graduação em Odontologia
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Odontologia
Programa de Pós-Graduação em Odontologia
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| bdtd@biblioteca.ufpb.br
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