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1.
Diabetes Care ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303636

RESUMO

OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes. RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed. RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs. CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

2.
Am J Clin Nutr ; 112(3): 631-643, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619242

RESUMO

BACKGROUND: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. OBJECTIVES: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. METHODS: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. RESULTS: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. CONCLUSIONS: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Índice Glicêmico , Carga Glicêmica , Adulto , Idoso , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
3.
Eur J Epidemiol ; 35(11): 1057-1067, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710289

RESUMO

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose-response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03-1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02-1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04-1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01-1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02-1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose-response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

4.
Cancer Res ; 80(9): 1885-1892, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32075798

RESUMO

Although ample evidence indicates that immune cell homeostasis is an important prognostic outcome determinant in patients with cancer, few studies have examined whether it also determines cancer risk among initially healthy individuals. We performed a case-cohort study including incident cases of breast (n = 207), colorectal (n = 111), lung (n = 70), and prostate (n = 201) cancer as well as a subcohort (n = 465) within the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. Relative counts of neutrophils, monocytes, and lymphocyte sublineages were measured by qRT-PCR. HRs and 95% confidence intervals were used to measure the associations between relative counts of immune cell and cancer risks. When relative counts of immune cell types were taken individually, a significant positive association was observed between relative counts of FOXP3+ regulatory T cells (Tregs) and lung cancer risk, and significant inverse associations were observed between relative CD8+ counts and risks of lung and breast cancer (overall and ER+ subtype). Multivariable models with mutual adjustments across immune markers showed further significant positive associations between higher relative FOXP3+ T-cell counts and increased risks of colorectal and breast cancer (overall and ER- subtype). No associations were found between immune cell composition and prostate cancer risk. These results affirm the relevance of elevated FOXP3+ Tregs and lower levels of cytotoxic (CD8+) T cells as risk factors for tumor development. SIGNIFICANCE: This epidemiologic study supports a role for both regulatory and cytotoxic T cells in determining cancer risk among healthy individuals.See related commentary by Song and Tworoger, p. 1801.


Assuntos
Neoplasias , Linfócitos T Reguladores , Estudos de Coortes , Epigênese Genética , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
5.
Int J Cancer ; 147(4): 1027-1039, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945199

RESUMO

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.

6.
Cancer Epidemiol Biomarkers Prev ; 29(3): 681-686, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31932413

RESUMO

BACKGROUND: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. METHODS: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: We observed lower mtDNA copy number with advancing age (P = 6.54 × 10-5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16-0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. CONCLUSIONS: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. IMPACT: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.

7.
Nutrients ; 11(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484340

RESUMO

A pro-coagulative state is related to increased risk of cardiovascular diseases but also certain cancers. Since experimental and smaller human studies suggest that diet, physical activity, and body weight may all affect coagulation, we evaluated associations between these lifestyle factors and hemostatic biomarkers in a population-based study. Cross-sectional baseline data from 2267 randomly selected participants of EPIC-Heidelberg (age range 35-65 years) was used. Fibrinogen, glycoprotein IIb/IIIa, P-selectin, thrombomodulin (TM), and thrombopoietin (TPO) were measured in baseline plasma samples. A score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention was created. Associations between the WCRF/AICR score as well as its individual components and hemostatic biomarkers were analyzed by linear regression models. Multivariable-adjusted geometric means (95% confidence intervals) of TM and TPO were higher with greater adherence to the WCRF/AICR recommendations (TM, lowest vs. highest score category: 2.90 (2.7,3.1) vs. 3.10 (2.9,3.3) ng/mL, plinear trend = 0.0001; TPO: 328 (302,356) vs. 348 (321,378) pg/mL, plinear trend = 0.0007). These associations were driven by lower alcohol and meat consumption among persons with higher WCRF/AICR scores. Our results indicate that lifestyle factors favorably affect TM and TPO, two hemostatic factors implicated in chronic disease development.


Assuntos
Dieta , Hemostasia/fisiologia , Estilo de Vida , Neoplasias/prevenção & controle , Trombomodulina/sangue , Trombopoetina/sangue , Academias e Institutos , Adulto , Biomarcadores , Estudos Transversais , Coleta de Dados , Feminino , Guias como Assunto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Estados Unidos
8.
Cancer Epidemiol Biomarkers Prev ; 28(6): 1089-1092, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160392

RESUMO

BACKGROUND: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up. METHODS: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors. RESULTS: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance. CONCLUSIONS: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems. IMPACT: The results do not support an association between education and risk of pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Estudos de Coortes , Escolaridade , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Neoplasias Pancreáticas/economia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
9.
Cancer Epidemiol Biomarkers Prev ; 28(7): 1221-1227, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31015200

RESUMO

BACKGROUND: While enhanced platelet activation and a procoagulant state may drive lung cancer progression and metastases, less is known about their role in earlier phases of cancer development. Thus, we evaluated whether prediagnostic biomarkers of platelet activation and coagulation are related to the risk of lung cancer in the prospective EPIC-Heidelberg Study using a case-cohort design. METHODS: Levels of fibrinogen, soluble glycoprotein (sGP) IIb/IIIa, soluble P-selectin (sP-selectin), soluble thrombomodulin (sTM), and thrombopoietin (TPO) were measured in baseline plasma samples of a random subcohort (n = 2,480) and incident cases of lung cancer (n = 190). Multivariable-adjusted Cox proportional hazards regression analyses were used to obtain HRs of lung cancer across quartiles of biomarker levels. RESULTS: Fibrinogen [HR highest vs. lowest quartile: 1.91 (95% confidence interval: 1.09-3.34)] and sP-Selectin [HR: 2.51 (1.39-4.52)] were significantly associated with lung cancer risk in multivariable adjusted Cox regression models. Adding both biomarkers to the established PLCOm2012 algorithm, which alone showed a C-statistic of 0.788, led to a slight increment in lung cancer risk prediction, with a C-statistic of 0.814. CONCLUSION: Our findings indicate that enhanced platelet activation and a procoagulative state contribute to lung carcinogenesis. IMPACT: The current prospective study supports the hypothesis of increased coagulation being a possible driver of lung carcinogenesis, as strong positive associations were found between two procoagulative markers, sP-Selectin and fibrinogen, with lung cancer risk. Both biomarkers could improve lung cancer risk prediction, but external validation of the results is needed.


Assuntos
Fibrinogênio/metabolismo , Selectinas/metabolismo , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
10.
Parkinsonism Relat Disord ; 62: 98-104, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30772279

RESUMO

INTRODUCTION: Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. METHODS: In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. RESULTS: We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. CONCLUSION: Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.


Assuntos
Adiposidade/fisiologia , Doença de Parkinson/patologia , Fumar/efeitos adversos , Circunferência da Cintura/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Modelos de Riscos Proporcionais , Fatores de Risco
11.
Int J Cancer ; 144(8): 1877-1887, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30259989

RESUMO

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.


Assuntos
Apolipoproteína A-II/sangue , Antígeno CA-19-9/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Estudos Prospectivos , Isoformas de Proteínas/análise , Isoformas de Proteínas/metabolismo , Curva ROC , Fatores de Tempo
12.
Int J Epidemiol ; 48(3): 912-925, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462234

RESUMO

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.


Assuntos
Fumar Cigarros/epidemiologia , Doença de Parkinson/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Idoso , Causalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Proteção , Fatores de Tempo
13.
Urology ; 120: 192-196, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29940234

RESUMO

OBJECTIVE: To examine if lower urinary tract symptom (LUTS) progression was related to anthropometric and lifestyle factors. MATERIAL AND METHODS: The analysis included 5495 men who participated in the EPIC-Heidelberg cohort (recruited 1994-1998) and who reported an International Prostate Symptom Score < 8 at follow-up 4 (FUP4, 2007-2009), had not reported taking α-adrenoreceptor antagonists or 5-α reductase inhibitors or prostate surgery for benign prostatic hyperplasia/LUTS treatment. LUTS progression was defined as an International Prostate Symptom Score ≥ 8 at FUP5 (2010-2012). Using logistic regression analysis, education, marital status, satisfaction with life, satisfaction with health, history of diabetes and of hypertension, smoking, alcohol consumption, body mass index (BMI), waist circumference, and physical activity were examined as potential LUTS risk factors adjusting for age. RESULTS: Increase in BMI between baseline and FUP4 of ≥ 2 BMI units was related to LUTS progression (odds ratio 1.30, 95% confidence interval 1.08-1.57) compared with stable BMI. Compared to men who were very satisfied with life at baseline, those who were satisfied (1.28, 1.11-1.47), unsatisfied (1.80, 1.31-2.46) or very unsatisfied with life (1.43, 0.62-3.34) were more likely to report LUTS progression. Men with longer education had higher odds of LUTS progression than men with primary education only (1.25, 1.06-1.48). Adjusting for BMI or lifestyle factors did not attenuate these associations. Smoking habits, alcohol consumption, physical activity, self-reported history of diabetes or hypertension, and marital status were not related with LUTS progression. CONCLUSION: Our results confirm some, but not all previously observed risk factors for LUTS progression.


Assuntos
Progressão da Doença , Estilo de Vida , Sintomas do Trato Urinário Inferior/epidemiologia , Envelhecimento , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Escolaridade , Exercício Físico , Alemanha/epidemiologia , Humanos , Hipertensão/epidemiologia , Masculino , Estado Civil , Pessoa de Meia-Idade , Satisfação Pessoal , Fatores de Risco , Fumar/epidemiologia , Inquéritos e Questionários , Circunferência da Cintura
14.
Artigo em Alemão | MEDLINE | ID: mdl-29487975

RESUMO

BACKGROUND: Cardiovascular and metabolic diseases are a major cause of mortality and loss of quality of life in Germany. Research into risk factors of these diseases requires large population-based cohort studies. Complete and accurate assessment of the incidence of cardiovascular and metabolic diseases is a key element for valid interpretation of the results from such studies. OBJECTIVE: Our aim was to identify population-based cohort studies with incidence of cardiovascular and metabolic diseases in Germany and to summarize their methods for assessment and classification of disease endpoints, including myocardial infarction, type 2 diabetes, stroke, heart failure, and arterial hypertension. METHODS: Within the framework of a workshop, representatives of the ascertained population-based cohort studies in Germany with incidence of cardiovascular or metabolic diseases were invited to present and to systematically provide information on their methods of endpoint identification. RESULTS: We identified eight studies from different regions in Germany with a total of 100,571 participants, aged 18-83 years at baseline. Self-reporting by study participants is the major source for further inquiries to assess disease endpoints in these studies. Most studies use additional data sources to verify the incidence of diseases, such as documents provided by the treating physician or hospital. CONCLUSIONS: Our results highlight the central role of self-reporting and the efforts associated with identification and verification of disease endpoints in cohort studies. They also provide a basis for future population-based studies that aim for standardized assessment of the incidence of cardiovascular and metabolic diseases.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Metabólicas/epidemiologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Alemanha/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Adulto Jovem
15.
Int J Cancer ; 143(3): 561-569, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29574909

RESUMO

While experimental evidence suggests potential carcinogenic effects of increased iron load, there is a lack of data on iron status and cancer risk from epidemiological studies. Here, we evaluated prediagnostic serum concentrations of ferritin, iron and transferrin as well as transferrin saturation (TSAT) in relation to cancer risk and mortality in a prospective study by multivariable Cox regression analyses. A case-cohort sample of the population-based EPIC-Heidelberg Study including a random subcohort (n = 2738) and incident cases of breast cancer (n = 627), prostate cancer (n = 554), lung cancer (n = 195), colorectal cancer (n = 256) and cancer death (n = 759) was used. Ferritin levels were inversely associated with breast cancer risk in the multivariable Cox regression model, with a hazard ratio (HR) of 0.67 [95% confidence interval: 0.49, 0.92] for women in the highest quartile compared to those in the lowest quartile. Neither ferritin nor the other markers of iron status were significantly associated with colorectal, prostate or lung cancer risk. An inverse association was observed between ferritin and total cancer mortality (HR: 0.70 [0.53, 0.92]). There were no significant overall associations between serum iron, transferrin or TSAT and cancer mortality. The present findings do not support the notion of increased iron load constituting a cancer risk factor in the general population. By contrast, our analyses revealed inverse associations between ferritin levels and breast cancer risk as well as cancer mortality.


Assuntos
Ferro/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Vigilância da População , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco
16.
Eur J Nutr ; 57(7): 2399-2408, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28733927

RESUMO

PURPOSE: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. METHODS: This study includes 373,293 men and women, 25-70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). RESULTS: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (-0.07 kg; 95% CI -0.12 to -0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92-0.98) or obese (RR 0.95; 95% CI 0.90-0.99) (both P trend <0.008). CONCLUSIONS: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.


Assuntos
Índice de Massa Corporal , Peso Corporal , Nozes , Obesidade/epidemiologia , Adulto , Idoso , Dieta , Ingestão de Energia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
17.
Clin Biochem ; 52: 117-122, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29108727

RESUMO

BACKGROUND: Circulating oxysterols have been proposed as biological markers of disease risk. However, within-person reproducibility of circulating oxysterols over time is not well established. METHODS: We evaluated the one-year reproducibility of 11 oxysterols and lanosterol among 30 postmenopausal women with repeat blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) - Heidelberg, Germany cohort. Liquid chromatography-mass spectrometry (LC/MS) was performed to quantify serum concentrations of 22R-hydroxycholesterol, 25-hydroxycholesterol, 24S-hydroxycholesterol, 27-hydroxycholesterol, 22S-hydroxycholeterol, 24,25-epoxycholesterol, 5α,6ß-dihydroxycholestanol, 7α-hydroxycholesterol, 5ß,6ß-epoxycholesterol, 5α,6α-epoxycholesterol, 24-dihydrolanosterol, and lanosterol. We evaluated Spearman correlations and intraclass correlation coefficients (ICCs) between quantifiable concentrations measured in repeat samples taken one-year apart to estimate within-person reproducibility. RESULTS: Spearman correlations (ICCs) over one year ranged from 0 (ICC=0.10) for 5ß,6ß-epoxycholesterol and 0.10 (ICC=0.20) for 5α,6α-epoxycholesterol, representing low within-person stability, to 0.81 (ICC=0.75) for 27-hydroxycholesterol and 0.86 (ICC=0.91) for 24S-hydroxycholesterol, representing relatively high within-person stability. Correlations between oxysterols and lanosterol ranged from 0.01 between 24S-hydroxycholesterol and lanosterol to 0.70 between 5α,6α-epoxycholesterol and 5ß,6ß-epoxycholesterol. CONCLUSIONS: Our results demonstrate that for 27-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 7α-hydroxycholesterol and lanosterol, a single serum measurement can reliably estimate average levels over a one-year period. Circulating oxysterols are of increasing interest in epidemiologic studies of chronic disease risk including cancer and cardiovascular disease. Our data suggest that within-person stability of oxysterols differs depending on the individual oxysterol evaluated. We identified four oxysterols and lanosterol as stable over time to inform the use of circulating oxysterols in epidemiologic studies.


Assuntos
Hidroxicolesteróis/análise , Lanosterol/análise , Oxisteróis/análise , Idoso , Idoso de 80 Anos ou mais , Colesterol/análogos & derivados , Colesterol/sangue , Cromatografia Líquida/métodos , Feminino , Alemanha , Humanos , Hidroxicolesteróis/sangue , Lanosterol/sangue , Pessoa de Meia-Idade , Oxisteróis/sangue , Pós-Menopausa , Estudos Prospectivos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
18.
Int J Cancer ; 142(6): 1189-1201, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29114875

RESUMO

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.


Assuntos
25-Hidroxivitamina D 2/sangue , Calcifediol/sangue , Neoplasias Pancreáticas/epidemiologia , Idoso , Estudos de Casos e Controles , Europa (Continente) , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Estudos Prospectivos , Medição de Risco , Estações do Ano
19.
Diabetes Care ; 41(2): 277-285, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29167213

RESUMO

OBJECTIVE: Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS: The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression. RESULTS: Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (ß = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (-0.019 [-0.043; 0.006]) or transferrin saturation (0.016 [-0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03). CONCLUSIONS: We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Dieta , Interação Gene-Ambiente , Ferro/metabolismo , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Europa (Continente)/epidemiologia , Feminino , Ferritinas/genética , Estudo de Associação Genômica Ampla , Proteína da Hemocromatose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transferrina/genética
20.
Am J Clin Nutr ; 106(1): 263-275, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28592605

RESUMO

Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.Objective: We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.Design: We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.Results: Thirteen observational studies met the eligibility criteria (n < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.


Assuntos
Diabetes Mellitus/etiologia , Dieta , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Fibras na Dieta/farmacologia , Comportamento Alimentar , Interação Gene-Ambiente , Estudos de Casos e Controles , Caveolina 2/genética , Diabetes Mellitus/genética , Dipeptidases/genética , Ingestão de Energia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Receptores dos Hormônios Gastrointestinais/genética , Fatores de Risco , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética
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