RESUMO
The p53 tumor-suppressor protein has a key role in the induction of cellular senescence, an important barrier to cancer development. However, very little is known about the physiological mediators of cellular senescence induced by p53. CEACAM1 is an immunoglobulin superfamily member whose expression is frequently lost in human tumors and exhibits tumor-suppressor features in several experimental systems, including Ceacam1 knockout mice. There is currently little understanding of the pathways and mechanisms by which CEACAM1 exerts its tumor-suppressor function. Here we report that CEACAM1 is strongly upregulated during the cellular response to DNA double-strand breaks (DSBs) starting from the lowest doses of DSB inducers used, and that upregulation is mediated by the ataxia telangiectasia mutated (ATM)/p53 pathway. Stable silencing of CEACAM1 showed that CEACAM1 is required for p53-mediated cellular senescence, but not initial cell growth arrest, in response to DNA damage. These findings identify CEACAM1 as a key component of the ATM/p53-mediated cellular response to DNA damage, and as a tumor suppressor mediating cellular senescence downstream of p53.
RESUMO
This study aimed to identify high support needs and their socio-demographic predictors to improve supportive care for newly diagnosed breast cancer patients. A cross-sectional study measured patients' needs and unsatisfied support needs by the supportive care needs survey (SCNS-34), administered after surgery, chemotherapy or radiotherapy. Socio-demographic, disease and treatment characteristics completed data collection. A total of 308 questionnaires were completed with a response rate of 88%. The most frequent support needs (73.3% of patients) related to information and the highest unsatisfied support needs to the management of emotions and daily life (36.3-39.6% of patients). Younger age predicted high and dissatisfied support needs (P < 0.05). Patients born outside Switzerland or with a lower level of education had more needs in daily living and psychological domains (P < 0.05). Being born outside Switzerland also predicted dissatisfaction with information provided. Being parent was a predictor of significant needs in the daily living domain after adjusting for disease and treatment characteristics (P= 0.01). Therefore, information, psychological and daily living support for newly diagnosed breast cancer patients should be strongly reinforced, particularly in patients being born outside Switzerland, those with children or being younger. For the latter, support in sexuality domain should also be emphasised.
Assuntos
Neoplasias da Mama/psicologia , Necessidades e Demandas de Serviços de Saúde , Assistência ao Paciente/normas , Apoio Social , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Inquéritos e Questionários , SuíçaRESUMO
QUESTION UNDER STUDY: Over the last decade the Swiss health care system has undergone several changes, resulting in stronger economic constraints, a heavier administrative workload and limited work autonomy for doctors. In this context we examined the change in burnout prevalence over time among Swiss doctors surveyed during this period. METHODS: Cross-sectional survey data collected by mail in 2002, 2004 and 2007 throughout the country were used. Measures included the Maslach Burnout Inventory (MBI), several socio-demographics (gender, living alone, having children), and work-related characteristics (number of years in current workplace, hours worked). Answers to the MBI were used to classify respondents into moderate (high score on either the emotional exhaustion or the depersonalisation/cynicism subscale) and high degree of burnout (scores in the range of burnout in all three scales). RESULTS: Rates of moderate-degree burnout increased from 33% to 42% among general practitioners (p = 0.002) and from 19% to 34% among paediatricians (p = 0.001) (high degree of burnout: 4% to 6% [p = 0.17] and 2% to 4% [p = 0.42] respectively). After adjustment for significant socio-demographic and work-related characteristics, an increased risk of moderate burnout was found for doctors surveyed in 2004 and 2007 (OR 1.6, 95%CI 1.3 to 2.0), general practitioners (OR 1.6, 95%CI 1.3 to 2.0) and French-speaking doctors (OR 1.5, 95%CI 1.3 to 1.9). An increased risk of high-degree burnout was found only for general practitioners (OR 1.8, 95%CI 1.05 to 3.0). CONCLUSIONS: Burnout levels among Swiss doctors have increased over the last decade, in particular among French-speaking doctors.
Assuntos
Esgotamento Profissional/epidemiologia , Reforma dos Serviços de Saúde/tendências , Programas Nacionais de Saúde/tendências , Inabilitação do Médico/estatística & dados numéricos , Adulto , Esgotamento Profissional/diagnóstico , Esgotamento Profissional/psicologia , Controle de Custos/tendências , Estudos Transversais , Características da Família , Feminino , Clínicos Gerais/psicologia , Clínicos Gerais/estatística & dados numéricos , Reforma dos Serviços de Saúde/economia , Inquéritos Epidemiológicos , Humanos , Medicina Interna/estatística & dados numéricos , Medicina Interna/tendências , Masculino , Oncologia/estatística & dados numéricos , Oncologia/tendências , Pessoa de Meia-Idade , Programas Nacionais de Saúde/economia , Pediatria/estatística & dados numéricos , Pediatria/tendências , Inventário de Personalidade/estatística & dados numéricos , Inabilitação do Médico/psicologia , Autonomia Profissional , Psicometria , Fatores de Risco , Fatores Socioeconômicos , Suíça , Carga de Trabalho/psicologia , Carga de Trabalho/estatística & dados numéricosRESUMO
Ovarian cancer accounts for a minority of female cancers but remains the leading cause of death from gynaecologic cancers and the fifth leading cause of all cancer-related deaths among women. More than two thirds of cases of ovarian cancer are diagnosed once the disease becomes symptomatic, i.e. at an advanced stage. Though early detection constitutes a legitimate aim, no screening approach has yet been shown to reduce ovarian cancer mortality. In particular, ovarian imagery with endovaginal ultrasonography and serum tumor markers (CA-125) dosage performed in asymptomatic individuals have not proven their efficacy. Screening of asymptomatic women is not therefore recommended because of the limited prevalence of ovarian cancer in the general population.
Assuntos
Programas de Rastreamento/métodos , Neoplasias Ovarianas/diagnóstico , Feminino , Humanos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia , Fatores de RiscoRESUMO
Surveillance following curative therapy for localised breast cancer has two major aims: 1) diagnosis of recurrence or a second tumor: regular interviews and physical examinations with a frequency adapted to each case, and yearly mammography (+/- ultrasonography), are the only recommended procedure. Additional screening is not indicated in asymptomatic patient. 2) Screening for complications and side effects due to treatment: tamoxifen treatment should be stopped one week prior to any surgery or long trip to avoid thromboembolic events, and any metrorrhagia should be investigated due to the risk for endometrial cancer. Osteoporosis and arthralgia are frequently observed with aromatase inhibitors.
Assuntos
Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/prevenção & controle , Feminino , Humanos , Mamografia , Recidiva Local de Neoplasia/diagnóstico , Exame FísicoRESUMO
Through an anonymized questionnaire we assessed the prevalence of complementary and alternative medicine (CAM) use in a series of cancer patients treated at the Geneva University Hospitals. 152 among the 300 sollicitated patients responded and 39 (26.5%) recognized to use CAM, particularly young, and moderate to highly educated patients. Patients justify their use of CAM to maximize caring ressources, to achieve physical or psychic relief. Most of them recognize to share these therapeutic options with their doctor. Satisfaction with traditional medicine as well as ignorance of CAM are the main arguments provided by non users. The specificity of our hospital context in which results were collected and the lack of a common and popular definition of CAM remain the main limitations of our enquiry.
Assuntos
Terapias Complementares/estatística & dados numéricos , Neoplasias/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Satisfação do Paciente , Relações Médico-Paciente , Inquéritos e QuestionáriosRESUMO
Using data from the Geneva Cancer Registry, we found that in 2002-2004, breast cancer incidence in women aged 25-39 years increased by 46.7% per year (95% CI: 7.1-74.0, P=0.015), which surveillance or detection bias may not fully explain.
Assuntos
Neoplasias da Mama/epidemiologia , Carcinoma/epidemiologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etiologia , Carcinoma/etiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The high prevalence of the disease, the absence of primary prevention and the wide accessibility to the PSA test have led to the promotion of prostate cancer screening in asymptomatic individuals. A critical appraisal of available data fails to support this enthousiasm: formal evidence demonstrating that radical treatment of infraclinical cancers through population screening reduce mortality is lacking. A large proportion of screen-detected cancers has a favourable biological behaviour and hence does not justify radical therapeutic options endowed with significant morbidity. A better understanding of the mechanisms governing tumor progression should provide means to develop markers allowing for an improved selection of high-risk patients susceptible to benefit from radical treatments.
Assuntos
Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapiaAssuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Proteínas Mutadas de Ataxia Telangiectasia , Estudos de Casos e Controles , Criança , Heterozigoto , Humanos , Polimorfismo Genético , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients =50 years, recorded between 1990 and 2001 at the Geneva familial breast cancer registry. We compared patients at high familial risk and low familial risk in terms of tumour characteristics, method of detection, treatment, survival and breast cancer mortality risk. Compared to patients at low familial risk (n=575), those at high familial risk (n=58) received significantly more often systemic therapy, especially for node-negative or receptor-positive disease. Five-year disease-specific survival rates of patients at high vs low familial risk were 86 and 90%, respectively. After adjustment, there was no difference in breast cancer mortality in general. A strong family history nonsignificantly increased breast cancer mortality in patients =40 years (adjusted hazard ratio (HR) 4.0, 95% CI 0.8-19.7) and in patients treated without chemotherapy (adjusted HR 2.7, 95% CI 0.6-12.5). A strong family history of breast cancer is associated with an increased use of systemic therapy in early-onset patients. Although a strong family history does not seem to affect survival in general, it may impair survival of very young patients and patients treated without adjuvant chemotherapy. Owing to the limited number of patients in this study, these results should be used only to generate hypotheses.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Adulto , Idade de Início , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Taxa de SobrevidaRESUMO
This study evaluates the risk of acute myeloid leukaemia (AML) in patients treated for breast cancer. We included all 6360 breast cancer patients that were recorded at the Geneva Cancer Registry between 1970 and 1999. Patients were followed for AML occurrence until December 2000. We calculated standardized incidence ratios of AML and identified factors modifying the risk of AML by multivariate Cox analysis. Twelve (0.2%) patients developed AML. In general, patients treated for breast cancer had a 3.5-fold (95% confidence interval (CI): 1.8-6.0) increased risk of developing AML compared with the general population. In particular, patients who were older than 70 years at breast cancer diagnosis and those treated with radiotherapy (with or without chemotherapy) had a significantly increased risk of developing AML. This population-based study confirms that radiotherapy increases the risk of AML. Due to the relatively low number of women treated with chemotherapy without radiotherapy and due to the infrequency of the disease, the question of whether chemotherapy alone increases this risk of AML cannot yet be answered.
Assuntos
Neoplasias da Mama/terapia , Leucemia Mieloide/epidemiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada/efeitos adversos , Feminino , Humanos , Incidência , Leucemia Mieloide/etiologia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , População , Radioterapia Adjuvante/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologiaRESUMO
BACKGROUND: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. PATIENTS AND METHODS: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (kappa) were calculated. RESULTS: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and kappa of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and kappa were 67%, 99%, and 0.66, respectively. CONCLUSIONS: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verification.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Sistema de Registros/estatística & dados numéricos , Sistema de Registros/normas , Adulto , Idoso , Relações Familiares , Feminino , Predisposição Genética para Doença , Humanos , Anamnese , Pessoa de Meia-Idade , Linhagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , SuíçaRESUMO
Inherited biallelic mutations of the ATM (ataxia-telangiectasia mutated) gene cause ataxia-telangiectasia, a rare autosomal recessive disorder associated with a high incidence of childhood leukaemias and lymphomas, suggesting that ATM gene alterations may be involved in lymphomagenesis. Loss of heterozygosity at 11q22-23 (location of the ATM gene) is a frequent event in sporadic lymphoid tumours, and several studies have reported a high prevalence of ATM gene alterations in diverse sporadic lymphoproliferative disorders, adding evidence to the postulated contribution of ATM in the pathogenesis of these tumours. This mini-review will summarize the recently published data concerning the ATM gene in sporadic lymphoid malignancies and will discuss the apparent paradox between the predominance of nonsense mutations observed in patient with ataxia-telangiectasia and the high proportion of missense alterations found in sporadic lymphoid tumours.
Assuntos
Linfoma/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Predisposição Genética para Doença , Humanos , Linfoma/etiologia , Mutação/fisiologia , Fenótipo , Proteínas Supressoras de TumorAssuntos
Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Tumor Mulleriano Misto/induzido quimicamente , Sistema de Registros , Tamoxifeno/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Feminino , Humanos , Incidência , Tumor Mulleriano Misto/epidemiologia , Fatores de Risco , Suíça/epidemiologia , Tamoxifeno/uso terapêuticoAssuntos
Neoplasias da Mama/genética , Lesões Pré-Cancerosas/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Proteínas Supressoras de TumorRESUMO
BACKGROUND: Increasing incidence of ductal carcinoma in situ (DCIS) confronts patients and clinicians with optimal treatment decisions. This multidisciplinary study investigates therapeutic modalities of DCIS in daily practice and provides recommendations on how to increase quality of care. PATIENTS AND METHODS: All women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from 1995 to 1999 were considered. Information concerned patient and tumor characteristics, treatment and outcome. Factors linked to therapy were determined using a case-control approach. Cases were women with treatment of interest and controls other women on the study. RESULTS: Most DCIS cases (62%) were discovered by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS), 18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%) chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction after mastectomy. Method of discovery, multifocality, tumor localization, size and differentiation were linked to the use of BCS or lymph node dissection. CONCLUSIONS: Because of important disparities in DCIS management, recommendations are made to increase quality of care, in particular to prevent axillary dissection or bilateral mastectomy and to increase the use of radiotherapy after BCS.
Assuntos
Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Estudos de Casos e Controles , Diferenciação Celular , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Excisão de Linfonodo , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Vigilância da População , Qualidade de Vida , Sistema de Registros , Fatores de Risco , Fatores SocioeconômicosRESUMO
In 1990, an international consensus was reached on the efficacy of adjuvant chemotherapy for lymph node positive (stage III) colon carcinoma (CC). This study evaluates the use and benefit of such therapy in routine health care practice. The study includes all patients with stage III CC treated by putative curative surgery (n = 182) recorded at the Geneva cancer registry between 1990 and 1996. Factors modifying chemotherapy use were determined by logistic regression, considering patients with chemotherapy as cases (n = 55) and others as controls (n = 127). The effect of chemotherapy on the 5-year survival was evaluated by the Cox model. Analyses were adjusted for possible confounders. The use of chemotherapy increased over the period (P(trend) < 0.001). Age strongly modulated chemotherapy use. In 1996, 54% of eligible patients received chemotherapy, this proportion fell to 13% after age 70. Decisions to use chemotherapy significantly depended on stage, grade and cancer site. The chance to be treated was non-significantly lower among individuals of low social class, widowed and foreigners. Chemotherapy significantly decreased mortality rates (Hazard ratio: 0.35, 95%CI: 0.18-0.68), independently of the prognostic factors and with similar benefit regardless of stage and age group. Strong beneficial effect of adjuvant chemotherapy on stage III CC can be achieved in routine practice. However, this study shows that it is probably not optimally utilised in Switzerland, particularly among the elderly.