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Master's Dissertation
DOI
10.11606/D.6.2007.tde-05122007-111306
Document
Author
Full name
Rossana Verónica Mendoza López
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Wunsch Filho, Victor (President)
Carvalho, Marcos Brasilino de
Eluf Neto, Jose
Title in Portuguese
Polimorfismos genéticos de invasão e metástase, inflamação e reparo de DNA e prognóstico de tumores de laringe
Keywords in Portuguese
Polimorfismos genéticos
Análise de sobrevida
Estudo de coorte
Tumores de laringe
Abstract in Portuguese
Introdução: O prognóstico dos carcinomas epidermóides de laringe é limitado e a taxa de sobrevida em cinco anos é menor que 70%. A relação de características clínicas e epidemiológicas tem sido investigada na sobrevida de pacientes com tumores de laringe, mas pouco se conhece sobre o efeito dos polimorfismos genéticos no prognóstico da doença. Objetivo: Estudar o papel dos polimorfismos genéticos de genes relacionados aos processos de invasão e metástase (MMP1 e MMP3), de inflamação (Interleucina 2, Interleucina 6, LTA) e reparo de DNA(XRCC1) no prognóstico do carcinoma epidermóide de laringe. Material e métodos: Coorte com 170 pacientes com carcinoma epidermóide de laringe,confirmados por exame anátomo-patológico. Os casos tiveram origem em estudo caso-controle conduzido em cinco hospitais de São Paulo, um hospital em Porto Alegre e outro em Goiânia. As informações sobre o status vital dos pacientes foram levantadas dos prontuários médicos e dos bancos de óbitos municipais e estaduais. A extração do DNA das amostras de sangue dos pacientes foi realizada pelo Instituto de Medicina Tropical da USP e a genotipagem dos polimorfismos genéticos pela Fundação Hemocentro de Ribeirão Preto da Faculdade de Medicina da USP. Resultados: Os polimorfismos genéticos estudados (MMP1 1607, MMP1 -519,MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 e XRCC1) não apresentaram efeitos com significância estatística na sobrevida global ou específica pela doença quando analisados isoladamente. Para a sobrevida global, o consumo excessivo de álcool, em g/L/dia, reduziu a sobrevida dos pacientes (80-119 g/L/dia: hazard ratio(HR)=4,0 intervalos com 95% de confiança (IC95%)=1,10-14,53; _120 g/L/dia: HR=5,6 IC95%=1,71-18,24). No modelo de Cox múltiplo, quando ajustados pelo polimorfismo genético MMP3 -1171, a sobrevida piorou para esses pacientes (80-119 g/L/dia: HR=4,9 IC95%=1,07-22,91; _120 g/L/dia: HR=6,3 IC95%=1,49-26,84). Para a sobrevida específica pela doença, o estadiamento clínico IV reduziu a sobrevida dos pacientes (HR=3,5 IC95%=1,67-7,28). No modelo de Cox múltiplo,com ajuste pelos polimorfismos genéticos IL6 -174 e MMP1 1607, a sobrevidaespecífica pela doença piorou para esses pacientes (HR=4,7 IC95%=1,38-16,25).Conclusões: Na coorte examinada, somente três dos oito polimorfismos genéticos estudados relacionaram-se com a sobrevida global e específica pela doença, porém apenas alterando o efeito dos valores dos HR brutos dos fatores consumo de álcool e estadiamento clínico, respectivamente na sobrevida global e sobrevida específica pela doença. Isoladamente, nenhum polimorfismo genético estudado interferiu na sobrevida dos pacientes com câncer de laringe.
Title in English
Influence of genetic polymorphisms related with invasion and metastasis, inflammation and repair of DNA and prognosis of laryngeal squamous cell carcinoma
Keywords in English
Cohort study
Genetic polymorphisms
Larynx cancer
Survival analysis
Abstract in English
Introduction: The prognosis of laryngeal squamous cell carcinoma is limited and survival rate is lower than 70%. The relationships between clinical and epidemiological characteristics have been fully investigated on the survival of patients with laryngeal tumors, but the effect of genetics polymorphisms on squamous cell carcinoma of larynx is not well-known. Objective: To study the role of genetic polymorphisms of genes related to the processes of invasion and metastasis (MMP1 and MMP3), inflammation (Interleukin 2, Interleukin 6, and LTA) and repair of DNA (XRCC1) in the prognosis of laryngeal squamous cell carcinoma. Material and methods: Cohort with 170 laryngeal squamous cell carcinoma patients with histological confirmation. The cases have their origin in a case-control study carried out in hospitals of Sao Paulo, Porto Alegre and Goiania. The information about vital status of patients had been raised from medical records. The extraction of DNA was carried out by Institute of Tropical Medicine of USP and genotyping was carried out by the Center of Cellular Therapy of the Hemocentro of Ribeirao Preto of Medical School of USP. Results: The studied genetic polymorphisms (MMP1 1607, MMP1 -519, MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 and XRCC1), separately analyzed, did not have any statistical significant effect on the overall and cause-specific survival. High levels of alcohol consumption (g/L/day) reduced the overall survival (80-119 g/L/day: hazard ratio(HR)=4.0 intervals with 95% of confidence (95%CI)=1.10-14.53; _120 g/L/day:HR=5.6 95%CI=1.71-18.24). Multiple Cox model revealed, when adjusted for MMP3 -1171 genetic polymorphism, lower survival for those patients (80-119g/L/day: HR=4.9 95%CI=1.07-22.91; _120 g/L/day: HR=6.3 95%CI=1.49-26.84). The clinical staging (CS) IV was a factor for low cause-specific survival (CS IV:HR=3.5 95%CI 1.67-7.28). In the multiple Cox model, adjusted for genetic polymorphism IL6 -174 and MMP1 1607, the survival of those patients droppe(HR=4.7 95%CI=1.38-16.25). Conclusions: In this cohort, only three of eight genetic polymorphisms studied were showed to be related with overall and causespecific survival, however only modifying the effect of unadjusted HR of alcohol consumption and tumor clinical staging in the overall and cause-specific survival respectively. None of the studied genetic polymorphisms, when analyzed separately,affected the survival of laryngeal cancer patients.
 
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Publishing Date
2007-12-10
 
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