by Chiu Yuk Lan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 127-133). / Abstract also in Chinese. / TABLE OF CONTENTS / ABSTRACT (ENGLISH) --- p.a / ABSTRACT (CHINESE) --- p.b / ACKNOWLEDGEMENTS --- p.iv / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Cancer in Food-service Workers --- p.1 / Chapter 1.2 --- Carcinogenicity of Cooking Fumes --- p.1 / Chapter 1.3 --- High Risk of Lung Cancer in Chinese Women --- p.2 / Chapter 1.4 --- Why do We Conduct This Study? --- p.3 / Chapter 1.5 --- Implication of This Study --- p.4 / Chapter 1.6 --- What Types of Cancer were Included in This Study? --- p.4 / Chapter 1.7 --- Aims and Hypothesis of This Study --- p.5 / Chapter 1.8. --- Outline of the Thesis --- p.5 / Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.8 / Chapter 2.1. --- Occupational Epidemiological Studies --- p.8 / Chapter 2.1.1 --- Studies of occupation and cancer occurrence based on routine records --- p.8 / Chapter 2.1.2 --- Retrospective cohort studies among food service workers --- p.21 / Chapter 2.1.3 --- Case-control studies --- p.27 / Chapter 2.1.4 --- Case reports --- p.29 / Chapter 2.1.5 --- Summary --- p.29 / Chapter 2.2. --- Mutagens and Carcinogens in Cooking Fumes --- p.39 / Chapter 2.2.1 --- Mutagens and carcinogens in cooking fumes --- p.40 / Chapter 2.2.2 --- Summary --- p.42 / Chapter CHAPTER 3 --- METHODS --- p.44 / Chapter 3.1 --- Study Design --- p.44 / Chapter 3.2 --- Study Population and Subjects --- p.46 / Chapter 3.3 --- Reference Population --- p.48 / Chapter 3.4 --- Sample Size Estimation --- p.48 / Chapter 3.5 --- Data Sources and Data Collection --- p.49 / Chapter 3.6 --- Data Processing --- p.53 / Chapter 3.7 --- Data Analyses --- p.54 / Chapter 3.7.1 --- Standardised proportional mortality ratio (SPMR) --- p.54 / Chapter 3.7.2 --- Adjusted' SPMRs --- p.56 / Chapter 3.7.3 --- Mortality odds ratio (MOR) --- p.58 / Chapter 3.8. --- Exploring if Smoking could be a Confounding Factor --- p.62 / Chapter CHAPTER 4 --- RESULTS --- p.64 / Chapter 4.1 --- Characteristics of the Food-service Workers --- p.64 / Chapter 4.2 --- Cancer Mortality Patterns of Food-service Workers --- p.69 / Chapter 4.3 --- Adjusted SPMRs --- p.72 / Chapter 4.4 --- Mortality Odds Ratios (MORs) --- p.76 / Chapter 4.5 --- Mortality Odds Ratios Using Multiply Reference Diseases --- p.77 / Chapter 4.6. --- Comparing SPMRs with MORs --- p.82 / Chapter 4.7. --- Internal Comparison --- p.83 / Chapter 4.8 --- Summary of Results --- p.90 / Chapter 4.9. --- Survey on Smoking and Drinking Prevalence among Current Food-service Workers --- p.92 / Chapter 4.9.1 --- Smoking habit --- p.92 / Chapter 4.9.2 --- Drinking habit --- p.94 / Chapter CHAPTER 5 --- DISCUSSION OF FINDINGS --- p.95 / Chapter 5.1 --- Outcomes for This Study --- p.95 / Chapter 5.1.2 --- Cancer risks for the kitchen workers --- p.96 / Chapter 5.1.3 --- Cancer risks for the outside kitchen workers --- p.102 / Chapter 5.2 --- Limitations of the Methods Adopted in the Present study --- p.107 / Chapter 5.2.1 --- Standardised proportional mortality ratio (SPMR) --- p.107 / Chapter 5.2.2 --- Morality odds ratio (MOR) --- p.109 / Chapter 5.3 --- Bias and Control --- p.111 / Chapter 5.3.1 --- Selection bias --- p.111 / Chapter 5.3.2 --- Information bias --- p.113 / Chapter 5.3.3 --- Confounding --- p.116 / Chapter 5.4 --- Implications from the Results of the Present Study --- p.117 / Chapter 5.5 --- Conclusion --- p.119 / APPENDIX --- p.121 / Appendix 1 --- p.121 / Appendix 2 --- p.123 / Appendix 3 --- p.124 / Appendix 4 --- p.125 / REFERENCES --- p.127

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.

INTRODUÇÃO: O estudo das vias moleculares e das alterações específicas responsáveis pela progressão desfavorável de pacientes com CCR parece essencial para o desenvolvimento de terapias mais efetivas. OBJETIVO: Comparar a expressão quantitativa dos genes TACSTD2, Ku70, KRAS mutante e SERIN1 em amostras de tecidos normal e tumoral de pacientes com CCR e relacionar sua expressão com variáveis clínico-patológicas. MÉTODOS: Foram estudados 37 pacientes com CCR submetidos à ressecção cirúrgica entre julho de 2005 e julho de 2009 e cujas amostras congeladas de tecidos tumoral e normal foram armazenadas em um banco de tecidos. Através da RT-PCR foi sintetizado o cDNA a partir do RNA extraído das amostras teciduais. A expressão dos genes TACSTD2, KRAS mutante, Ku70 e SERIN1 foi quantificada pela técnica de PCR em tempo real. RESULTADOS: A expressão do KRAS mutante foi maior no tecido tumoral do que no normal (p = 0,024). A expressão tumoral dos genes Ku70, TACSTD2 e SERIN1 foi respectivamente menor, igual e maior que o tecido normal, porém sem significância estatística. Associação estatisticamente significativa também foi observada entre idade e expressão de KRAS mutante no tecido normal e tumores pouco diferenciados e expressão de Ku70 no tecido normal. Não foram observadas outras associações estatisticamente significativas. CONCLUSÕES: A expressão do KRAS mutante no tecido tumoral é maior do que no tecido normal (p = 0,024) na casuística de 37 pacientes com CCR estudados através da técnica de PCR em tempo real. / INTRODUCTION: Knowledge of the molecular pathways and of the specific alterations responsible for the unfavorable progression of patients with CCR appears essential for the development of more effective therapies. PURPOSE: To compare the quantitative expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 in samples of normal and tumoral tissues of patients with CCR and to relate their expression to clinicopathologic characteristics. METHODS: 37 patients with CCR were studied. The patients had been operated on between July 2005 and July 2009, and their frozen samples of tumoral and normal tissues had been stored in a tissue bank. The expression of the genes TACSTD2, mutant KRAS, Ku70 and SERIN1 was quantified through the technique of real time polymerase chain reaction. RESULTS: The mutant KRAS expression was higher in the tumoral tissue than in the normal tissue (p = 0,024). Although not significant, the tumoral expression of the genes Ku70, TACSTD2 and SERIN1 was respectively lower, equal to, and higher than in the normal tissue. Statistically significant association was also observed between age and mutant KRAS expression in normal tissue and between poorly-differentiated tumors and Ku70 expression in normal tissue. No other statistically significant associations were observed. CONCLUSIONS: Tumoral tissues express mutant KRAS at higher levels than normal tissues in the casuistic of 37 patients with CCR studied through the technique of PCR real time.