The copy number variation of GSTM1 as a promising prognostic factor of oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to investigate whether the copy number variation (CNV) of GSTM1 and GSTT1 is related to the occurrence of oral squamous cell carcinoma (OSCC) relapses, along the overall and progression-free survival of patients. STUDY DESIGN: A total of 234 OSCC patients were recruited from the Heliópolis hospital and they were distributed among 4 groups according to the occurrence of OSCC relapses. Fisher exact test, odds ratio (OR), and 95% CI were determined to investigate the chances of OSCC progression. The overall and progression-free survival were analyzed by the Kaplan-Meier and Cox regression methods. RESULTS: The CNV of GSTM1 analysis showed that one copy of the gene was associated with reduced chances of OSCC recurrences (OR 0.45; 95% CI 0.25-0.81) and decreased the risk of tumor progression (HR 0.50; 95% CI 0.33-0.75). Furthermore, one copy of GSTM1 was related to a better overall survival rate (HR 0.63; 95% CI 0.0.44-0.91). Regarding the CNV of GSTT1, no copies were associated with the chances of OSCC relapses, the overall survival, or the progression-free survival. CONCLUSIONS: The CNV of GSTM1 may be applied to predict OSCC relapses and aid the treatment management, which might improve the survival rates of patients.

Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk.

BACKGROUND: Genetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. METHODS: A total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heliópolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. RESULTS: Most OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24-0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. CONCLUSION: The findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.

Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population.

BACKGROUND: Cigarette consumption has been identified as the main non-etiological factor in head and neck cancer (HNC) development. One of the main compounds in cigarettes is nicotine, which binds directly to nicotine acetylcholine receptors (nAchRs) in the body, which are encoded by different genes of the CHRNA family. Polymorphisms in some of these genes have been studied in relation to the risk of HNC and cigarette consumption intensity. The aim of this study was to evaluate whether there were associations between the CHRNA3 (rs578776) and CHRNA5 (rs16969968) polymorphisms and HNC risk and between the polymorphisms and the intensity of cigarette consumption. METHODS: A total of 1,067 individuals from Heliopolis Hospital in São Paulo were investigated, including 619 patients with HNC and 448 patients without diagnosed tumors. All participants answered a questionnaire about sociodemographic information and cigarette consumption data. The polymorphisms were determined by TaqMan genotyping by real-time PCR. RESULTS: The polymorphisms studied, rs578776 (CHRNA3) and rs16969968 (CHRNA5), did not have an association with HNC risk, but the rs16969968 homozygous genotype was associated with increased cigarette consumption intensity (OR 1.93, 95% CI 1.05-3.58). CONCLUSION: The polymorphism CHRNA5 can be considered an indirect risk factor for neoplasms in these Brazilian samples when cigarette consumption increased.

Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis.

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.

[Interaction between dietary intake and GSTM1 and GSTT1 polymorphisms in head and neck cancer risk: a case-control study in São Paulo, Brazil]. / Interação entre consumo alimentar e polimorfismos da GSTM1 e GSTT1 no risco para o câncer de cabeça e pescoço: estudo caso-controle em São Paulo, Brasil.

A hospital-based case-control study was conducted to investigate the potential interaction between dietary factors and polymorphisms in phase II metabolic enzymes GSTM1 and GSTT1, associated with head and neck cancer risk. The study included 103 histologically confirmed incident cases and 101 controls. Food intake was estimated with a validated food frequency questionnaire. The gene polymorphisms were evaluated by PCR. Increased risk was observed in the highest tertile of beef consumption in the presence of the GSTM1 (OR = 10.79; 95%CI: 2.17-53.64) and GSTT1 null alleles (OR = 3.41; 95%CI: 0.43-27.21). Assessment of dietary intake considering the ratio between animal product and vegetable consumption showed OR = 2.35 (95%CI: 0.27-19.85) in the intermediate tertile and OR = 3.36 (95%CI: 0.41-27.03) in the highest tertile. The results suggest a possible interaction between meat intake and GSTM1/GSTT1 polymorphisms in modulating the risk of head and neck cancer, influenced by vegetable consumption.

Interação entre consumo alimentar e polimorfismos da GSTM1 e GSTT1 no risco para o câncer de cabeça e pescoço: estudo caso-controle em São Paulo, Brasil / Interaction between dietary intake and GSTM1 and GSTT1 polymorphisms in head and neck cancer risk: a case-control study in São Paulo, Brazil

O objetivo foi investigar a interação entre fatores dietéticos e polimorfismos de enzimas de metabolização de xenobióticos (GSTM1 e GSTT1) associadas ao câncer de cabeça e pescoço em um estudo caso controle de base hospitalar, no Município de São Paulo, Brasil. Participaram 103 casos incidentes, histologicamente confirmados, e 101 controles. O consumo alimentar foi obtido por um questionário de frequência alimentar validado. Os polimorfismos GSTM1 e GSTT1 foram avaliados pelo método PCR. Observou-se aumento de risco no mais alto tercil de consumo de carne bovina na presença do alelo nulo da GSTM1 (OR = 10,79; IC95 por cento: 2,17-53,64) e GSTT1 (OR = 3,41; IC95 por cento: 0,43-27,21). Considerando-se a razão entre alimentos de origem animal e vegetal, verificou-se para o tercil intermediário a OR = 2,02 (IC95 por cento: 0,24-16,0) e no tercil superior OR = 3,23 (IC95 por cento: 0,40-25,92). Os resultados apontam para uma possível interação entre o consumo de carne e variantes polimórficas dos genes GSTM1 e GSTT1 na modulação do risco para o câncer de cabeça e pescoço, influenciados pelo consumo de alimentos de origem vegetal.

A hospital-based case-control study was conducted to investigate the potential interaction between dietary factors and polymorphisms in phase II metabolic enzymes GSTM1 and GSTT1, associated with head and neck cancer risk. The study included 103 histologically confirmed incident cases and 101 controls. Food intake was estimated with a validated food frequency questionnaire. The gene polymorphisms were evaluated by PCR. Increased risk was observed in the highest tertile of beef consumption in the presence of the GSTM1 (OR = 10.79; 95 percentCI: 2.17-53.64) and GSTT1 null alleles (OR = 3.41; 95 percentCI: 0.43-27.21). Assessment of dietary intake considering the ratio between animal product and vegetable consumption showed OR = 2.35 (95 percentCI: 0.27-19.85) in the intermediate tertile and OR = 3.36 (95 percentCI: 0.41-27.03) in the highest tertile. The results suggest a possible interaction between meat intake and GSTM1/GSTT1 polymorphisms in modulating the risk of head and neck cancer, influenced by vegetable consumption.

Structures constituting the sound source after the treatment of early glottic cancer.

INTRODUCTION: We indicate the exclusive radiation therapy as initial approach for T1a glottic tumors, and the frontolateral laryngectomy for the tumors staged as T1b and selected T2 glottic tumors. The videolaryngostroboscopy is a useful tool to analyze the laryngeal structural changes and compensatory motion after the therapeutic approach. OBJECTIVES: To evaluate the endolaryngeal structures of patients who participate in the vibratory sound source after the early glottic cancer treatment through the videolaryngostroboscopy. METHODS: It was a retrospective transversal study in which 20 patients who underwent exclusive radiation therapy and 25 patients who underwent frontolateral laryngectomy were analyzed by means of videolaryngostroboscopy. The radiation doses ranged from 5000 to 7020 cGy in the radiation therapy group. The mucosal wave and the vibratory source components were evaluated. RESULTS: All of the irradiated patients presented vibratory behavior, and hyperfunction was occasionally observed in four cases. The mucosal wave source was glottic in 18 cases and mixed in two cases. In the laryngectomy group, 10 supraglottic sources, 10 glottic sources, and five mixed sources were identified. Among the 10 cases of supraglottic source, eight patients presented global constriction and two patients presented medial constriction. Among the five cases of mixed source, two patients presented global constriction, one patient presented medial constriction, and one patient presented anteroposterior constriction. Regarding the number of anatomical structures presenting vibratory pattern, five patients had two structures, four patients had three structures, and one patient had four structures. CONCLUSION: Patients who underwent radiation therapy recruit less supraglottic structures as vibratory source than the patients undergoing vertical laryngectomy.

Polymorphisms in alcohol metabolizing genes and the risk of head and neck cancer in a Brazilian population.

AIMS: The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC. METHODS: A hospital-based case-control study was conducted in São Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital. RESULTS: Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol >30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11). CONCLUSIONS: The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655 g/L/day.

Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer.

BACKGROUND: Alcohol intake and tobacco smoke, in addition to other environmental and genetic factors, have been associated with head and neck cancer. We evaluated the role of metabolic enzyme polymorphisms on the risk of head and neck cancer in a hospital-based case-control study. METHODS: CYP1A1MspI, CYP2E1PstI, GSTM1, and GSTT1polymorphisms were evaluated in 103 histologically confirmed head and neck cancer cases and 102 controls by means of polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: GSTM1null increased the risk of head and neck cancer (odds ratio [OR], 2.2; 95% confidence interval [95% CI], 1.24-3.79), oral cancer (OR, 2.8; 95% CI, 1.28-5.98), and pharyngeal cancer (OR, 2.2; 95% CI, 1.08-4.63). CYP2E1PstI polymorphism indicated a risk for oral cancer (OR, 3.6; 95% CI, 1.29-11.56). The joint effect of GSTM1 null and CYP1A1 polymorphism increased the risk of head and neck cancer (OR, 2.4; 95% CI, 1.13-5.10). CONCLUSIONS: GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.

Sobrevida após recidiva intratável do carcinoma epidermóide de cabeça e pescoço / Survival after unsalvageable recurrence of head and neck cancer

OBJETIVO: Avaliar a sobrevida em pacientes com câncer de cabeça e pescoço recidivado e sem possibilidade de tratamento curativo. MÉTODO: Foram revisados os prontuários dos pacientes com carcinoma epidermóide de boca, orofaringe, hipofaringe e laringe tratados cirurgicamente (tumor primário e esvaziamento cervical) entre 1978 e 2001, e selecionados 140 com recidiva da doença acompanhados até o óbito pelo câncer. Após 1999, 30 pacientes receberam cuidados paliativos de uma equipe multidisciplinar. Foi avaliado o intervalo de tempo entre a recidiva não resgatável e o óbito, considerando o sítio primário, estadiamento inicial, sobrevida livre de doença e cuidados paliativos. Os resultados foram expressos em medianas e médias, com os respectivos quartis e percentis. RESULTADOS: A sobrevida livre de doença apresentou média de 30 semanas. A sobrevida média após a recidiva foi de 17 semanas (Q25-75 por cento = 8 a 34 semanas). Dezessete pacientes (12 por cento) sobreviveram por mais de 12 meses após a recidiva. O sítio primário, estadiamento inicial, local da recidiva, sobrevida livre de doença e os cuidados paliativos não influenciaram a sobrevida após a recidiva. CONCLUSÃO: A sobrevida após uma recidiva não resgatável é similar ao relatado para os pacientes não tratados. Os cuidados paliativos não aumentaram a sobrevida destes pacientes.

Esvaziamento cervical no tratamento do carcinoma epidermóide de lábio / Neck dissection in the treatment of squamous cell carcinoma of the lip

O carcinoma epidermóide de lábio geralmente é diagnosticado em fase inicial e as metástases linfonodais são pouco freqüentes. OBJETIVO: Avaliar a incidência e a localização das metástases linfonodais no carcinoma epidermóide de lábio. FORMA DE ESTUDO: Estudo retrospectivo, série de casos. CASUíSTICA E MÉTODO: Revisão de prontuários de 78 pacientes com carcinoma epidermóide de lábio, sem tratamento prévio, atendidos no período de 1990 a 2001. Foi avaliada a relação do tamanho do tumor primário, grau de diferenciação e comprometimento da comissura labial com a presença de metástases linfonodais, bem como a localização das metástases. RESULTADOS: As metástases linfonodais foram observadas em 7 por cento dos tumores até 3 cm e em 41 por cento nos tumores maiores do que 3 cm (p=0,002). Dez pacientes apresentavam metástases, sendo que todos estes tinham metástases no nível I e apenas 2 tinham metástases em outros níveis. Os pacientes submetidos ao esvaziamento eletivo apresentavam metástases apenas no nível I. CONCLUSÃO: As metástases são infreqüentes nos tumores menores do que 3 cm. Quando presentes, as metástases habitualmente acometem o nível I, portanto o esvaziamento suprahioideo pode ser indicado no tratamento eletivo do pescoço.

Correlação clínico-patológica entre a presença da necrose microscópica e a revolução da carcinoma epidermóide inicial da laringe / Clinical-pathologic correlation between the presence of microscopic necrosis and evolution of initial laryngeal squamous cell carcinoma

Introdução: Fazer a análise da presença da necrose tumoral microscópica no tumor primário inicial da laringe e correlacioná-la com algumas características clínicas e histopatológicas, objetivando identificar seu impacto na evolução. Forma de estudo: Retrospectivo clínico. Material e métodos: Estudo retrospectivo das fichas médicas e revisão dos cortes histológicos obtidos de 49 casos de carcinomas epidermóides da laringe, estadiados como T1 e T2, tratados no Serviço de Cirurgia de Cabeça e Pescoço do Complexo Hospitalar Heliópolis, de São Paulo/ SP, entre janeiro/1978 e dezembro/1997. Resultados: Houve forte associação entre a presença de necrose microscópica e a característica infiltrativa da lesão primária (p=0,004), lesões na supraglote (p=0,021), estádio clínico T2 (p=0,04), ocorrência de metástase cervical (p=0,04) e lesões menos diferenciadas (p=0,025). Aqueles casos que apresentaram necrose microscópica tenderam à melhor evolução. Conclusão: As informações obtidas do nosso estudo sugerem que a necrose por si, como classificada por técnicas histopatológicas, pode não ter influência exclusiva ou reflexo no crescimento volumétrico, refletindo a taxa de crescimento tumoral, mas pode estar relacionada a outros fatores tumorais e/ou do hospedeiro como a morte celular programada.

Correlaçäo clínico-epidemiológica do carcinoma epidermóide (T1 e T2) da laringe: estudo de 73 casos / Clinical and epidemiological correlation of initial laryngeal squamous cells carcinoma (T1 and T2): study of 73 cases

As modificações funcionais e estruturais causadas pelo câncer na laringe estão bem estabelecidas e reconhecidas. Porém, os erros na avaliação da laringe do paciente não são infrequêntes. Esses erros são tanto de incorreta interpretação de sinais e sintomas quanto o não reconhecimento de alterações anatômicas visíveis na propedêutica armada. Por considerar escassos os trabalhos apresentados na literatura que tratam da relação dos dados clínicos e a epidemiologia do câncer de laringe, propusemo-nos a analisar e correlacionar algumas variáveis clínicas e epidemiológicas, com objetivo de uma melhor compreensão da história natural e formas de apresentação do câncer laríngeo. Forma do estudo: Clínico retrospectivo. Método: Estudo retrospectivo a partir da análise dos prontuários de 73 pacientes portadores de carcinoma epidermóide inicial da laringe (T1 e T2), virgens de tratamento e submetidos à cirurgia no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis /SP, no período de setembro/1977 a dezembro /1997. Resultados: Encontramos predomínio de pacientes do sexo masculino, entre a sexta e a sétima décadas de vida, tabagistas e etilistas, com tumores glóticos. Para aqueles portadores de lesão glótica o sintoma predominante foi a disfonia; já para os pacientes com tumores supraglóticos, sintomas relacionados à via digestiva preponderaram. Em relação à característica macroscópica, as lesões na glote eram preferencialmente vegetantes, enquanto que na supraglote eram infiltrativas. Conclusões: A evolução clínica do câncer laríngeo é uma reprodução fiel da progressão tumoral dentro da região acometida, com sintomas distintos para os diferentes sítios. Assim, sua manifestação é bem representativa da alteração morfológica provocada no órgão