RESUMO
The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95 percent confidence intervals (95 percentCI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6 percent). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95 percentCI = 0.15-1.81) and T/T (HR = 0.22; 95 percentCI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95 percentCI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95 percentCI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95 percentCI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95 percentCI = 0.26-1.78) and larynx cancer (HR = 0.93; 95 percentCI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/mortalidade , Neoplasias de Cabeça e Pescoço/mortalidade , /genética , /genética , Polimorfismo Genético/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Coortes , Carcinoma de Células Escamosas/etiologia , Intervalo Livre de Doença , Escolaridade , Genótipo , Neoplasias de Cabeça e Pescoço/etiologia , Prognóstico , Fatores de Risco , Fumar/efeitos adversosRESUMO
The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Neoplasias de Cabeça e Pescoço/mortalidade , Interleucina-2/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/etiologia , Estudos de Coortes , Intervalo Livre de Doença , Escolaridade , Feminino , Genótipo , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: A higher burden of head and neck cancer has been reported to affect deprived populations. This study assessed the association between socioeconomic status and head and neck cancer, aiming to explore how this association is related to differences of tobacco and alcohol consumption across socioeconomic strata. METHODS: We conducted a case-control study in São Paulo, Brazil (1998-2006), including 1017 incident cases of oral, pharyngeal and laryngeal cancer, and 951 sex- and age-matched controls. Education and occupation were distal determinants in the hierarchical approach; cumulative exposure to tobacco and alcohol were proximal risk factors. Outcomes of the hierarchical model were compared with fully adjusted ORs. RESULTS: Individuals with lower education (OR 2.27; 95% CI 1.61 to 3.19) and those performing manual labour (OR 1.55; 95% CI 1.26 to 1.92) had a higher risk of disease. However, 54% of the association with lower education and 45% of the association with manual labour were explained by proximal lifestyle exposures, and socioeconomic status remained significantly associated with disease when adjusted for smoking and alcohol consumption. CONCLUSIONS: Socioeconomic differences in head and neck cancer are partially attributable to the distribution of tobacco smoking and alcohol consumption across socioeconomic strata. Additional mediating factors may explain the remaining variation of socioeconomic status on head and neck cancer.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Disparidades nos Níveis de Saúde , Fumar/epidemiologia , Classe Social , Idoso , Brasil/epidemiologia , Intervalos de Confiança , Feminino , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Risco AjustadoRESUMO
Cancers of the upper aerodigestive tract (UADT: oral cavity, oropharynx, hypopharynx, larynx, esophagus) have high incidence rates all over the world and they are especially frequent in some parts of Latin America. In this study, we have evaluated the role of the consumption of maté, a hot herb-based beverage, based on 1168 UADT squamous-cell carcinoma cases and 1,026 frequency-matched controls enrolled from four centers in Brazil and Argentina. The effect of maté drinking on the risk of head-and-neck cancers was borderline significant. A significant effect was observed only for cancer of the esophagus (OR 3.81 (95% CI 1.75-8.30)). While duration of maté drinking was associated with the risk of all UADT cancers, the association with cumulative maté consumption was restricted to esophageal cancer (p-value of linear trend 0.006). The analyses of temperature at which maté was drunk were not conclusive. The increased risk associated with maté drinking was more evident in never-smokers and never-alcohol drinkers than in other individuals. Our study strengthens the evidence of an association between maté drinking and esophageal cancer; the hypothesis of an association with other UADT cancers remains to be clarified.
Assuntos
Bebidas/efeitos adversos , Ingestão de Líquidos , Neoplasias Esofágicas/complicações , Neoplasias de Cabeça e Pescoço/complicações , Ilex paraguariensis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Brasil/epidemiologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Feminino , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/metabolismo , Proteoma/metabolismo , Anexina A5/metabolismo , Apoptose , Proliferação de Células , Regulação para Baixo , Eletroforese em Gel Bidimensional , Fibroblastos/metabolismo , Genômica , Células Hep G2 , Humanos , Queratinas/metabolismo , Neoplasias Bucais/genética , Hibridização de Ácido Nucleico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Células Estromais/metabolismo , Vimentina/metabolismoRESUMO
Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.
Assuntos
Receptores ErbB/genética , Neoplasias Esofágicas/epidemiologia , Genes p53 , Neoplasias de Cabeça e Pescoço/epidemiologia , Estilo de Vida , Adulto , Idoso , Estudos de Casos e Controles , Cocarcinogênese , Neoplasias Esofágicas/genética , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , América do Sul/epidemiologiaRESUMO
AIMS: Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. METHODS AND RESULTS: Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. CONCLUSIONS: ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.
Assuntos
Anexina A1/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anexina A1/análise , Anexina A1/genética , Western Blotting , Carcinoma de Células Escamosas/patologia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Reports of uterine cancer deaths that do not specify the subsite of the tumor threaten the quality of the epidemiologic appraisal of corpus and cervix uteri cancer mortality. The present study assessed the impact of correcting the estimated corpus and cervix uteri cancer mortality in the city of São Paulo, Brazil. The epidemiologic assessment of death rates comprised the estimation of magnitudes, trends (1980-2003), and area-level distribution based on three strategies: i) using uncorrected death certificate information; ii) correcting estimates of corpus and cervix uteri mortality by fully reallocating unspecified deaths to either one of these categories, and iii) partially correcting specified estimates by maintaining as unspecified a fraction of deaths certified as due to cancer of "uterus not otherwise specified". The proportion of uterine cancer deaths without subsite specification decreased from 42.9% in 1984 to 20.8% in 2003. Partial and full corrections resulted in considerable increases of cervix (31.3 and 48.8%, respectively) and corpus uteri (34.4 and 55.2%) cancer mortality. Partial correction did not change trends for subsite-specific uterine cancer mortality, whereas full correction did, thus representing an early indication of decrease for cervical neoplasms and stability for tumors of the corpus uteri in this population. Ecologic correlations between mortality and socioeconomic indices were unchanged for both strategies of correcting estimates. Reallocating unspecified uterine cancer mortality in contexts with a high proportion of these deaths has a considerable impact on the epidemiologic profile of mortality and provides more reliable estimates of cervix and corpus uteri cancer death rates and trends.
Assuntos
Atestado de Óbito , Neoplasias Uterinas/mortalidade , Adulto , Brasil/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores Socioeconômicos , Neoplasias do Colo do Útero/mortalidadeRESUMO
Reports of uterine cancer deaths that do not specify the subsite of the tumor threaten the quality of the epidemiologic appraisal of corpus and cervix uteri cancer mortality. The present study assessed the impact of correcting the estimated corpus and cervix uteri cancer mortality in the city of São Paulo, Brazil. The epidemiologic assessment of death rates comprised the estimation of magnitudes, trends (1980-2003), and area-level distribution based on three strategies: i) using uncorrected death certificate information; ii) correcting estimates of corpus and cervix uteri mortality by fully reallocating unspecified deaths to either one of these categories, and iii) partially correcting specified estimates by maintaining as unspecified a fraction of deaths certified as due to cancer of "uterus not otherwise specified". The proportion of uterine cancer deaths without subsite specification decreased from 42.9 percent in 1984 to 20.8 percent in 2003. Partial and full corrections resulted in considerable increases of cervix (31.3 and 48.8 percent, respectively) and corpus uteri (34.4 and 55.2 percent) cancer mortality. Partial correction did not change trends for subsite-specific uterine cancer mortality, whereas full correction did, thus representing an early indication of decrease for cervical neoplasms and stability for tumors of the corpus uteri in this population. Ecologic correlations between mortality and socioeconomic indices were unchanged for both strategies of correcting estimates. Reallocating unspecified uterine cancer mortality in contexts with a high proportion of these deaths has a considerable impact on the epidemiologic profile of mortality and provides more reliable estimates of cervix and corpus uteri cancer death rates and trends.
Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Atestado de Óbito , Neoplasias Uterinas/mortalidade , Brasil/epidemiologia , Fatores Socioeconômicos , Neoplasias do Colo do Útero/mortalidadeRESUMO
Genomics is expanding the horizons of epidemiology, providing a new dimension for classical epidemiological studies and inspiring the development of large-scale multicenter studies with the statistical power necessary for the assessment of gene-gene and gene-environment interactions in cancer etiology and prognosis. This paper describes the methodology of the Clinical Genome of Cancer Project in São Paulo, Brazil (CGCP), which includes patients with nine types of tumors and controls. Three major epidemiological designs were used to reach specific objectives: cross-sectional studies to examine gene expression, case-control studies to evaluate etiological factors, and follow-up studies to analyze genetic profiles in prognosis. The clinical groups included patients' data in the electronic database through the Internet. Two approaches were used for data quality control: continuous data evaluation and data entry consistency. A total of 1749 cases and 1509 controls were entered into the CGCP database from the first trimester of 2002 to the end of 2004. Continuous evaluation showed that, for all tumors taken together, only 0.5% of the general form fields still included potential inconsistencies by the end of 2004. Regarding data entry consistency, the highest percentage of errors (11.8%) was observed for the follow-up form, followed by 6.7% for the clinical form, 4.0% for the general form, and only 1.1% for the pathology form. Good data quality is required for their transformation into useful information for clinical application and for preventive measures. The use of the Internet for communication among researchers and for data entry is perhaps the most innovative feature of the CGCP. The monitoring of patients' data guaranteed their quality.