RESUMO
BACKGROUND AND PURPOSE: Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. METHODS: We conducted pooled analyses of eight international, prospective cohort studies, including 351 565 individuals (120 688 men and 230 877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. RESULTS: During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously. CONCLUSIONS: Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.
Assuntos
Esclerose Lateral Amiotrófica/mortalidade , Cafeína , Café , Medição de Risco , Chá , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
RATIONALE: We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. METHODS: Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. RESULTS: Two phenotypes were identified in 454 patients, which we named 'uninflamed' (N=218) and 'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The 'reactive phenotype' was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). CONCLUSIONS: Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS.
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Biomarcadores/sangue , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/mortalidade , Idoso , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Análise por Conglomerados , Feminino , Humanos , Unidades de Terapia Intensiva , Interferon gama/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Inibidor 1 de Ativador de Plasminogênio/sangue , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
Insulin-like growth factors (IGFs) have been associated with growth, body size, physical activity and colorectal cancer (CRC). We hypothesized that variants in IGF-related genes increase the CRC susceptibility associated with a larger body size and a lack of physical activity. We assessed this in The Netherlands Cohort Study. Participants (n = 120852) completed a baseline questionnaire on diet and cancer. ~75% returned toenail clippings. Using a case-cohort approach and 16.3 years of follow-up, toenail DNA from 3768 subcohort members and 2580 CRC cases was genotyped. We aggregated unfavorable alleles (potentially increasing CRC risk) for 18 single nucleotide polymorphisms in 8 genes into a sum score. The sum score (in tertiles) and an IGF1 19-CA repeat polymorphism (19/19, 19/non-19 and non-19/non-19 repeats) in combination with body size (mostly in tertiles) and (non-)occupational physical activity (>12, 8-12 and <8 kJ/min in the job and >90, >60-90, >30-60 and ≤30 min/day) were analyzed by Cox regression. Increasingly higher hazard ratios (HRs) for CRC were observed for a larger adult body mass index, larger trouser size and tallness in the presence of more unfavorable alleles in men. HRs (95% confidence intervals) for joint effects were 1.55 (1.06-2.25), 1.78 (1.29-2.46) and 1.48 (1.01-2.17), respectively. In women, variant repeat alleles halved CRC risk irrespective of body size and physical activity. Almost no interactions tested significant. To conclude, a larger body size was a CRC risk factor in men in the presence of an accumulation of unfavorable alleles in IGF-related genes, but interactions were generally nonsignificant.
Assuntos
Tamanho Corporal/fisiologia , Neoplasias Colorretais/epidemiologia , Fator de Crescimento Insulin-Like I/genética , Atividade Motora/fisiologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Neoplasias Colorretais/genética , Dieta , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: As sodium, potassium and fluid intake are related to hypertension, an established risk factor for renal cell cancer (RCC), they may be independent risk factors for RCC. METHODS: The Netherlands Cohort Study (NLCS) with case-cohort design included 120,852 participants aged 55-69 years. At baseline, diet and lifestyle were assessed with questionnaires. After 17.3 years of follow-up, 485 RCC cases and 4438 subcohort members were available for analyses. RESULTS: Sodium intake increased RCC risk (P-trend=0.03), whereas fluid and potassium intake did not. For high sodium and low fluid intake, the RCC risk additionally increased (P-interaction=0.02). CONCLUSION: Sodium intake is a potential risk factor for RCC, particularly if fluid consumption is low.
Assuntos
Carcinoma de Células Renais/patologia , Dieta , Neoplasias Renais/dietoterapia , Potássio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Idoso , Carcinoma de Células Renais/epidemiologia , Estudos de Coortes , Comportamento Alimentar , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: To date, only a few risk factors for pancreatic cancer have been established. We examined prospectively relations between several medical conditions and pancreatic cancer incidence. METHODS: In 1986, 120 852 participants completed a baseline questionnaire on cancer risk factors, including several self-reported physician diagnosed medical conditions. At baseline, a random subcohort of 5000 participants was selected using a case-cohort approach for analysis. After 16.3 years of follow-up, 448 pancreatic cancer cases (63% microscopically confirmed) were available for analysis. RESULTS: Diabetes mellitus type II and hepatitis were positively associated with pancreatic cancer risk (multivariable-adjusted hazard ratio: 1.79; 95% confidence interval: 1.12-2.87 and hazard ratio: 1.37; 95% confidence interval: 1.04-1.81, respectively). Furthermore, a positive trend in risk with increasing years of diagnosis of diabetes (P=0.004) and of hepatitis (P=0.02) was observed. However, an inverse association was observed between hypertension and pancreatic cancer risk, this was found among microscopically confirmed cases only (hazard ratio: 0.66; 95% confidence interval: 0.49-0.90), while years since diagnosis of hypertension significantly decreased cancer risk (P for trend=0.02). CONCLUSION: In this prospective study, a positive association was observed between self-reported physician diagnosed diabetes mellitus type II and hepatitis and pancreatic cancer risk, whereas an inverse association was observed with hypertension.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Idoso , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.
Assuntos
Neoplasias do Endométrio/etiologia , Tumor Mulleriano Misto/etiologia , Sarcoma/etiologia , Neoplasias Uterinas/etiologia , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Tumor Mulleriano Misto/epidemiologia , Obesidade/complicações , Prognóstico , Fatores de Risco , Sarcoma/epidemiologia , Estados Unidos/epidemiologia , Neoplasias Uterinas/epidemiologiaRESUMO
BACKGROUND: We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS: Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P ≤ 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.
Assuntos
Instabilidade Cromossômica/genética , Neoplasias Colorretais/genética , Ilhas de CpG/genética , Instabilidade de Microssatélites , Idoso , Neoplasias Colorretais/diagnóstico , Metilação de DNA/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inquéritos e QuestionáriosRESUMO
Ovarian cancer is a highly lethal disease. Many researchers have, therefore, attempted to identify high risk populations. In this perspective, numerous genetic association studies have been performed to discover common ovarian cancer susceptibility variants. Accordingly, there is an increasing need to synthesize the evidence in order to identify true associations. A comprehensive and systematic assessment of all available data on genetic susceptibility to sporadic ovarian cancer was carried out. The evidence of statistically significant findings was evaluated based on the number of positive replications, the ratio of positive and negative studies, and the false-positive report probability (FPRP). The authors reviewed three genome-wide association studies (GWAS) and 147 candidate gene studies, published from 1990 to October 2010, including around 1100 genetic variants in more than 200 candidate genes and 20 intergenic regions. Genetic variants with the strongest evidence for an association with ovarian cancer include the rs2854344 in the RB1 gene and SNPs on chromosomes 9p22.2, 8q24, 2q31, and 19p13. Promising genetic pathways for ovarian cancer include the cell cycle, DNA repair, sex steroid hormone and oncogenic pathway. Concluding, this review shows that many genetic association studies have been performed, but only a few genetic variants show strong evidence for an association with ovarian cancer. More research is needed to elucidate causal genetic variants, taking into consideration gene-gene and gene-environment interactions, combined effects of common and rare variants, and differences between histological subtypes of this cancer.
Assuntos
Predisposição Genética para Doença , Neoplasias Ovarianas/genética , Ciclo Celular , Reparo do DNA , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Ovarianas/etiologia , Polimorfismo de Nucleotídeo Único , Receptores Androgênicos/genéticaRESUMO
BACKGROUND: Prospective data on red and processed meat in relation to risk of subtypes of esophageal and gastric cancer are scarce. We present analyses of association between red and processed meat and the risk of esophageal and gastric cancer subtypes within The Netherlands Cohort Study on Diet and Cancer. DESIGN: 120 852 individuals aged 55-69 years were recruited in 1986, and meat intake was assessed using a 150-item food frequency questionnaire. After 16.3 years of follow-up, 107 esophageal squamous cell carcinomas, 145 esophageal adenocarcinomas, 163 gastric cardia adenocarcinomas, 489 gastric non-cardia adenocarcinomas, and 3923 subcohort members were included in a case-cohort analysis. RESULTS: Processed as well as red meat intake was positively associated with esophageal squamous cell carcinoma in men. Hazard ratios for highest versus lowest quintile of processed and red meat were 3.47 [95% confidence intervals (CI): 1.21-9.94; P for trend: 0.04] and 2.66 (95% CI: 0.94-7.48; P for trend: 0.06), respectively. No association was seen for adenocarcinomas or gastric cancer subtypes or for any of the four subtypes among women. CONCLUSION: Our findings suggest that red and processed meat consumption is associated with increased risk of esophageal squamous cell carcinoma in men but not with cancers of other esophageal and gastric subtypes.
Assuntos
Adenocarcinoma/etiologia , Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Produtos da Carne/efeitos adversos , Neoplasias Gástricas/etiologia , Idoso , Animais , Bovinos , Dieta , Feminino , Cavalos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Ovinos , Estatísticas não Paramétricas , Sus scrofaRESUMO
OBJECTIVE: Alcohol consumption and cigarette smoking may be differentially associated with oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). However, because this was based on retrospective studies, these hypotheses were examined in a prospective cohort. METHODS: The prospective Netherlands Cohort Study consists of 120 852 participants who completed a baseline questionnaire on diet and other cancer risk factors in 1986. After 16.3 years of follow-up, 107 OSCC, 145 OAC, 164 GCA and 491 GNCA cases were available for analysis using Cox proportional hazards models and the case-cohort approach. RESULTS: The multivariable adjusted incidence rate ratio (RR) for OSCC was 4.61 (95% CI 2.24 to 9.50) for > or = 30 g ethanol/day compared with abstainers (p trend <0.001), while no associations with alcohol were found for OAC, GCA or GNCA. Compared with never smokers, current smokers had RRs varying from 1.60 for GCA to 2.63 for OSCC, and were statistically significant or borderline statistically significant. Frequency, duration and pack-years of smoking were independently associated with risk of all four cancers. A positive interaction was found between alcohol consumption and smoking status regarding OSCC risk. The RR for current smokers who consumed >15 g/day of ethanol was 8.05 (95% CI 3.89 to 16.60; p interaction = 0.65), when compared with never smokers who consumed <5 g/day of ethanol. CONCLUSIONS: This prospective study found alcohol consumption to be associated with increased risk of only OSCC. Cigarette smoking was associated with risk of all four cancers.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Esofágicas/etiologia , Fumar/efeitos adversos , Neoplasias Gástricas/etiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Cárdia , Cocarcinogênese , Métodos Epidemiológicos , Neoplasias Esofágicas/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fumar/epidemiologia , Neoplasias Gástricas/epidemiologiaRESUMO
The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies.
Assuntos
Terapia Genética , Doenças Retinianas , Análise Custo-Benefício , Humanos , Países Baixos , Doenças Retinianas/terapia , Avaliação da Tecnologia BiomédicaRESUMO
BACKGROUND: Current risk models for renal cell carcinoma (RCC) based on clinicopathological factors are sub-optimal in accurately identifying high-risk patients. Here, we perform a head-to-head comparison of previously published DNA methylation markers and propose a potential prognostic model for clear cell RCC (ccRCC). PATIENTS AND METHODS: Promoter methylation of PCDH8, BNC1, SCUBE3, GREM1, LAD1, NEFH, RASSF1A, GATA5, SFRP1, CDO1, and NEURL was determined by nested methylation-specific PCR. To identify clinically relevant methylated regions, The Cancer Genome Atlas (TCGA) was used to guide primer design. Formalin-fixed paraffin-embedded (FFPE) tissue samples from 336 non-metastatic ccRCC patients from the prospective Netherlands Cohort Study (NLCS) were used to develop a Cox proportional hazards model using stepwise backward elimination and bootstrapping to correct for optimism. For validation purposes, FFPE ccRCC tissue of 64 patients from the University Hospitals Leuven and a series of 232 cases from The Cancer Genome Atlas (TCGA) were used. RESULTS: Methylation of GREM1, GATA5, LAD1, NEFH, NEURL, and SFRP1 was associated with poor ccRCC-specific survival, independent of age, sex, tumor size, TNM stage or tumor grade. Moreover, the association between GREM1, NEFH, and NEURL methylation and outcome was shown to be dependent on the genomic region. A prognostic biomarker model containing GREM1, GATA5, LAD1, NEFH and NEURL methylation in combination with clinicopathological characteristics, performed better compared to the model with clinicopathological characteristics only (clinical model), in both the NLCS and the validation population with a c-statistic of 0.71 versus 0.65 and a c-statistic of 0.95 versus 0.86 consecutively. However, the biomarker model had limited added prognostic value in the TCGA series with a c-statistic of 0.76 versus 0.75 for the clinical model. CONCLUSION: In this study we performed a head-to-head comparison of potential prognostic methylation markers for ccRCC using a novel approach to guide primers design which utilizes the optimal location for measuring DNA methylation. Using this approach, we identified five methylation markers that potentially show prognostic value in addition to currently known clinicopathological factors.
Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Metilação de DNA/genética , Epigenômica/métodos , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biomarcadores Tumorais/genética , Humanos , Prognóstico , Medição de RiscoRESUMO
Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian cancer among postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. Information on reproductive history and exogenous hormone use was obtained through a self-administered questionnaire at baseline in 1986. After 16.3 years of follow-up, 375 cases and 2,331 subcohort members were available for case-cohort analysis. Ovarian cancer risk was reduced for parous women, with increasing parity, and for hysterectomized women. Moreover, the authors found evidence that oral contraceptive use is protective against ovarian cancer, even when initiated at an older age. In addition, a reduced risk was observed for each year reduction in age at natural menopause and per year reduction in total menstrual life span. A small increased risk was observed with prolonged time to pregnancy, but no difference was found between ever-married nulliparous women and never-married nulliparous women. Moreover, no associations were observed for age at first birth, age at menarche, age at first and last use of oral contraceptives, and use of hormone replacement therapy.
Assuntos
Anticoncepcionais Orais Hormonais/administração & dosagem , Terapia de Reposição Hormonal , Neoplasias Ovarianas/epidemiologia , Pós-Menopausa/fisiologia , História Reprodutiva , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Histerectomia , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/metabolismo , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/metabolismo , Paridade/fisiologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: Associations between cardiovascular mortality and air pollution and noise together were investigated. METHODS: Data from the ongoing Netherlands Cohort Study on Diet and Cancer (120,852 subjects; follow-up 1987-1996) were used. Cox proportional hazard analyses were conducted for the association between cardiovascular mortality and exposure to black smoke, traffic intensity on the nearest road and road traffic noise at the home address. RESULTS: The correlations between traffic noise and background black smoke, and traffic intensity on the nearest road were moderate at 0.24 and 0.30, respectively. Traffic intensity was associated with cardiovascular mortality, with highest relative risk (95% confidence interval) for ischaemic heart disease (IHD) mortality being 1.11 (1.03 to 1.20) (increment 10,000 motor vehicles/24 h). Relative risks for black smoke concentrations were elevated for cerebrovascular (1.39 (0.99 to 1.94)) and heart failure mortality (1.75 (1.00 to 3.05)) (increment 10 microg/m(3)). These associations were insensitive to adjustment for traffic noise. There was an excess of cardiovascular mortality in the highest noise category (>65 dB(A)), with elevated risks for IHD (1.15 (0.86 to 1.53)) and heart failure mortality (1.99 (1.05 to 3.79)). After adjustment for black smoke and traffic intensity, noise risk reduced to unity for IHD mortality and was slightly reduced for heart failure mortality. CONCLUSIONS: Associations between black smoke concentrations and traffic intensity on the nearest road with specific cardiovascular causes of death were not explained by traffic noise in this study.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Exposição Ambiental/efeitos adversos , Veículos Automotores/estatística & dados numéricos , Ruído dos Transportes/efeitos adversos , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Arritmias Cardíacas/mortalidade , Transtornos Cerebrovasculares/mortalidade , Estudos de Coortes , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Países Baixos/epidemiologia , Modelos de Riscos Proporcionais , Emissões de Veículos/análise , Emissões de Veículos/toxicidadeRESUMO
Sirtuin 1 (SIRT1) is an energy-sensing protein, which may affect tumorigenesis. We used SIRT1 variants as time-independent indicators of SIRT1 involvement in carcinogenesis and we studied two tagging SIRT1 variants in relation to colorectal cancer (CRC) risk. We also evaluated known energy balance-related CRC risk factors within SIRT1 genotype strata. The Netherlands Cohort Study includes 120,852 individuals and has 20.3 years follow-up (case-cohort: nsubcohort = 5000; nCRC cases = 4667). At baseline, participants self-reported weight, weight at age 20, height, trouser/skirt size reflecting waist circumference, physical activity, and early life energy restriction. SIRT1 rs12778366 and rs10997870 were genotyped in toenail DNA available for ~75% of the cohort. Sex- and subsite-specific Cox hazard ratios (HRs) showed that the rs12778366 CC versus TT genotype decreased CRC and colon cancer risks in women (HRCRC = 0.53, 95% confidence interval: 0.30-0.94) but not men. Multiplicative interactions were observed between SIRT1 variants and energy balance-related factors in relation to CRC endpoints, but the direction of associations was not always conform expectation nor specific to one genotype stratum. In conclusion, these results support SIRT1 involvement in colon cancer development in women. No conclusions could be made regarding a modifying effect of SIRT1 variants on associations between energy balance-related factors and CRC risk.
Assuntos
Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 1/genética , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Autorrelato , Fatores Sexuais , Circunferência da CinturaRESUMO
BACKGROUND/OBJECTIVES: The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets. SUBJECTS/METHODS: The Netherlands Cohort Study-Meat Investigation Cohort (NLCS-MIC)- is an analytical cohort of 11 082 individuals including 1133 self-reported vegetarians (aged 55-69 years at baseline). At baseline (1986), subjects completed a questionnaire on dietary habits and other risk factors for cancer and were classified into vegetarians (n=691), pescetarians (n=389), 1 day per week (n=1388), 2-5 days per week (n=2965) and 6-7 days per week meat consumers (n=5649). RESULTS: After 20.3 years of follow-up, 279 lung, 312 postmenopausal breast and 399 prostate cancer cases (including 136 advanced) were available for analyses. After adjustment for confounding variables, we found no statistically significant association between meat consumption groups and the risk of lung cancer. As well, no significant associations were observed for postmenopausal breast and overall prostate cancer. After adjustment for confounders, individuals consuming meat 1 day per week were at a 75% increased risk of advanced prostate cancer compared with 6-7 days per week meat consumers (95%CI 1.03-2.97). CONCLUSIONS: Vegetarians, pescetarians and 1 day per week meat consumers did not have a reduced risk of lung, postmenopausal breast and overall prostate cancer compared with individuals consuming meat on a daily basis after taking confounders into account.
Assuntos
Neoplasias da Mama/epidemiologia , Dieta Vegetariana , Dieta , Neoplasias Pulmonares/epidemiologia , Carne , Neoplasias da Próstata/epidemiologia , Idoso , Animais , Comportamento Alimentar , Feminino , Peixes , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Pós-Menopausa , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
In the Netherlands, childhood leukaemia is recorded by the Dutch Childhood Leukaemia Study Group (DCLSG, set up in 1972) and by nine regional cancer registries which together form the Netherlands Cancer Registry (NCR, set up in 1989). The data files from the incidence years 1989-1992 of the two registries were linked in order to evaluate accuracy and completeness and to calculate and equalise the incidence rates for childhood leukaemia in The Netherlands. Unlinked records or records with disagreements (birth date, sex, type of leukaemia and incidence date) were checked by the DCLSG and by the regional cancer registries. The DCLSG recorded 431 cases of childhood leukaemia, while the NCR recorded 434 cases. After record linkage and review of the cases, it was concluded the 445 records should have been recorded as childhood leukaemia. The NCR had recorded 425 of the 445 correct cases (95.5%), but had missed 20 cases (4.5%). The DCLSG had recorded 431 of the 445 correct cases (96.9%) and had missed 14 cases (3.1%). In addition, the NCR had recorded 9 cases incorrectly as childhood leukaemia. Part of the disagreement was caused by differences in coding rules (definition of non-Hodgkin's lymphoma (NHL) and the myelodysplastic syndrome versus leukaemia). It could be concluded that the quality and completeness of the two registries was very high. Regular comparison of the recorded data will help to reveal the inherently problematic disagreement between definitions and coding.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Sistema de Registros/normas , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais/normas , Feminino , Humanos , Incidência , Lactente , Masculino , Países Baixos/epidemiologia , Sensibilidade e EspecificidadeRESUMO
The aim of this study was to determine characteristics of the trends in incidence of and mortality from cutaneous malignant melanoma in The Netherlands. We used incidence data from the Netherlands Cancer Registry since 1989 and the causes of death registry of Statistics Netherlands since 1950. Data were age-adjusted and age-specific rates were calculated. Age-period-cohort modelling was applied to the mortality data. Between 1989 and 1998, age-adjusted incidence rates increased, mainly among those aged 45 years and older. Incidence rates were highest in the North-West and lowest in the South-East. Mortality rates increased in all age-categories, but more so among males than females. For women, an age-period model fitted the data, with decreasing relative risks after 1972. Age-period-cohort models were needed for males. The most likely explanation for the higher incidence is increasing intermittent over-exposure to ultraviolet (UV) radiation. The regional differences in melanoma incidence rates would correspond with host characteristics opportunities for and recreational exposure. Melanomas were detected at earlier stages in females, possibly explaining the flattening out of the female mortality rates.
Assuntos
Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Mortalidade/tendências , Países Baixos/epidemiologia , Características de Residência , Distribuição por Sexo , Neoplasias Cutâneas/epidemiologiaRESUMO
The first results are presented of the newly established Netherlands Cancer Registry, which covers the whole Dutch population (approximately 15 million people). The registry receives data on incident cancer cases from nine autonomous regional cancer registries. Notification occurs primarily through the national registry of all pathology and haematology departments, with additional reporting by medical records' departments of all hospitals. Data on cancer patients are abstracted directly from the medical records by trained registration clerks. In the years 1989-1990, the most common cancer sites among males were cancers of the lung, prostate and colon. For females, breast cancer ranked first, followed by cancer of the colon and lung. A comparison with age-adjusted (world standard population) incidence rates reported by other western cancer registries showed a relatively high incidence of lung cancer among males (72.9 per 100,000) and breast cancer among females (76.2 per 100,000). Through its near completeness and the high quality of the registered data, the Netherlands Cancer Registry offers excellent opportunities for epidemiological and clinical research.
Assuntos
Neoplasias/epidemiologia , Neoplasias da Mama/epidemiologia , Feminino , Neoplasias Gastrointestinais/epidemiologia , Humanos , Incidência , Leucemia/epidemiologia , Linfoma não Hodgkin/epidemiologia , Masculino , Países Baixos/epidemiologia , Sistema de Registros , Neoplasias do Sistema Respiratório/epidemiologia , Fatores Sexuais , Neoplasias Urogenitais/epidemiologiaRESUMO
Age at diagnosis has been proven to be an important determinant of the choice of initial treatment for several sites of cancer. Elderly patients are more likely to receive no treatment or less intensive treatment modalities. This study analysed the influence of age on treatment choice and survival in patients diagnosed with cervical cancer. This population-based study used data on 1176 new cases of invasive cervical cancer diagnosed in the period of 1986-1996 from three regional cancer registries in the Netherlands. All available information on treatment and survival (on 1 January 1998) was recorded. Relative survival rates were calculated according to the Hakulinen method. Relative risks (RR) for excess mortality due to the diagnosis of cervical cancer were calculated with a regression model for relative survival rates. Only 5% of the patients aged 70 years and older (n=224) were diagnosed with stage IA disease, compared with 11 and 30% of the patients aged 50-69 years and 49 years and younger, respectively. Almost 50% of the 70+ patients with stage IB-IIA were treated with radiotherapy as a single treatment modality, whereas 64% of the patients aged < or =49 years were treated with surgery alone. In all age groups, treatment for advanced stage disease (stage > or =IIB) was radiotherapy alone. No treatment was given to 10% of the patients aged 70 years and older, 5% of those aged 50-69 years and 1% of those aged 49 years and younger. Five-year relative survival was 69% (95% Confidence Interval (CI): 66-72%) and differed significantly (P=0.001) with age (70+ years: 49%; 50-69 years 58%; < or =49 years: 81%). Multivariate analyses on a subset of patients showed that age was not an independent prognostic factor, whereas stage and treatment modality were very important prognostic factors. Although elderly cancer patients were sometimes treated differently from younger patients, this was in accordance with the guidelines. Relative survival rates differed significantly by age. The multivariate analyses on the subset of patients also revealed that excess mortality increased with age. However, when adjustment was made for stage and treatment, this difference disappeared. The influence of treatment on survival is likely to be due to the selection of patients based on other characteristics, such as tumour volume, comorbidity and performance status.