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1.
Eur J Nutr ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909140

RESUMO

PURPOSE: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks. METHODS: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort, followed up for nearly 20 years. There were 3292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status, and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension. RESULTS: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend < 0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model, a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001). CONCLUSIONS: Our data suggest that adhering to a PD based on fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension.

2.
J Am Heart Assoc ; 9(23): e015121, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33190573

RESUMO

Background High body mass index (BMI) and low physical activity are associated with increased risk of hypertension. Few studies have assessed their joint impact or the relation of physical activity and hypertension among individuals within a healthy BMI range. The objective of this study was to investigate the associations between physical activity and hypertension across strata of BMI. Methods and Results We used data from the E3N (Etude Epidémiologique de femmes de la Mutuelle Générale de l´Education) cohort, a French prospective study of women aged 40 to 65 years. We included participants who completed a diet history questionnaire and who did not have prevalent hypertension at baseline, resulting in a total of 41 607 women. Questionnaires assessed time spent undertaking various types of physical activity. Hypertension cases were self-reported. Cox models were used to calculate hazard ratios (HRs) for physical activity. Associations were assessed over strata of BMI. Among the 41 607 included women, 10 182 cases of hypertension were identified in an average follow-up time of 14.5 years. Total physical activity was associated with a lower hypertension risk in women within the high-normal BMI range (BMI, 22.5-24.9) (HRQuartile 1-Quartile 4, 0.89; 95% CI, 0.79-0.99). An inverse relationship was observed between sports (HRsports >2 hours, 0.87; 95% CI, 0.83-0.93), walking (HRwalk >6.5 hours, 0.94; 95% CI, 0.90-1.00), and gardening (HRgardening >2.5 hours, 0.94; 95% CI, 0.89-0.99). Sports were associated with a reduced risk of hypertension in women with a healthy weight, but evidence was weaker in overweight/obese or underweight women. Conclusions Women with a healthy weight were those who could benefit most from practicing sports, and sports provided the largest risk reduction compared with other types of activity.

3.
Diabetes Care ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203707

RESUMO

OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

4.
PLoS Med ; 17(10): e1003394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33064751

RESUMO

BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

5.
Diabetes Care ; 43(11): 2660-2667, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868270

RESUMO

OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis. RESULTS: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes. CONCLUSIONS: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.

6.
BMJ ; 370: m2194, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641421

RESUMO

OBJECTIVE: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. DESIGN: Prospective case-cohort study. SETTING: Populations from eight European countries. PARTICIPANTS: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. MAIN OUTCOME MEASURE: Incident type 2 diabetes. RESULTS: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. CONCLUSIONS: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.


Assuntos
Ácido Ascórbico/sangue , Carotenoides/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Frutas , Verduras , Biomarcadores/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Dieta , Europa (Continente) , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
Nutrients ; 12(7)2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32610657

RESUMO

Most studies on dietary polyphenol intake and type 2 diabetes (T2D) risk have focused on total or specific subclasses of polyphenols. Since polyphenols are often consumed simultaneously, the joint effect of an intake of multiple subclasses should be explored. We aimed to identify profiles of the dietary polyphenol subclasses intake associated with T2D. A total of 60,586 women from the Etude Epidémiologique auprès de femmes de l'Education Nationale (E3N) cohort study were followed for 20 years between 1993 and 2014. T2D cases were identified and validated. The individual energy-adjusted daily intakes of 15 subclasses of polyphenols were estimated at baseline using a food frequency questionnaire and the PhenolExplorer database. We used Bayesian profile regression to perform the clustering of the covariates by identifying exposure profiles of polyphenol intakes and, simultaneously, link these to T2D risk by using multivariable Cox regression models. We validated 2740 incident T2D cases during follow-up, and identified 15 distinct clusters with different intake profiles and T2D risk. When compared to the largest cluster (n = 6298 women), higher risks of T2D were observed in three of those clusters, which were composed of women with low or medium intakes of anthocyanins, dihydroflavonols, catechins, flavonols, hydroxybenzoic acids, lignans, and stilbenes. One cluster (n = 4243), characterized by higher intakes of these polyphenol subclasses, exhibited lower T2D risk when compared to the reference cluster. These results highlight the importance of a varied diet of polyphenol-rich foods such as nuts, fruits, and vegetables to prevent T2D risk.

8.
Epidemiol Health ; : e2020036, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512663

RESUMO

Purpose: Previous studies yielded controversial findings on the association of testosterone with mortality in older men. Heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, and differential associations according to causes of death. Methods: We used data from a random subsample of the Three-City study (3C) in which hormones were measured in 338 men ≥65 years without metabolic syndrome, followed-up during 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (95% CIs). Results: Over the follow-up, 130 men died (30 from cardiovascular disease, 45 from cancer, 55 from other causes). The association of testosterone with mortality showed significant heterogeneity across causes of death (p=0.027 and p=0.022, for total and bioavailable testosterone, respectively). Higher testosterone level was associated with increased cardiovascular mortality (HR for 1-SD increase: 1.86, 95% CI: 1.28-2.71, and 1.50, 95% CI: 1.04-2.17, for total and bioavailable testosterone, respectively). By contrast, there was no significant association of testosterone with mortality from cancer and other causes. Conclusion: Our data suggest that the association of testosterone with mortality in men without metabolic syndrome might be differential according to the cause of death. These findings may explain part of the heterogeneity across studies on the relation between testosterone and mortality.

9.
Nutr J ; 19(1): 62, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32586324

RESUMO

INTRODUCTION: Previous studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI. METHODS: Data from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship. RESULTS: During 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII >  3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5-21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed. CONCLUSION: Evidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women.

10.
Diabetologia ; 62(12): 2222-2232, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31396661

RESUMO

AIMS/HYPOTHESIS: Diet is one of the main lifestyle-related factors that can modulate the inflammatory process. Surprisingly the dietary inflammatory index (DII) has been little investigated in relation to type 2 diabetes, and the role of BMI in this relationship is not well established. We studied this association and the role of BMI in the inflammatory process in a large population-based observational study. METHODS: A total of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort study were followed for 20 years. Incident type 2 diabetes cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases, and 3292 incident cases were validated. The DII was derived from a validated food frequency questionnaire. Multivariable Cox regression models estimated HRs and 95% CIs between DII and incident type 2 diabetes. Interactions were tested between DII and BMI on incident type 2 diabetes and a mediation analysis of BMI was performed. RESULTS: Higher DII scores, corresponding to a higher anti-inflammatory potential of the diet, were associated with a lower risk of type 2 diabetes. Compared with the 1st quintile group, women from the 2nd quintile group (HR 0.85 [95% CI 0.77, 0.94]) up to the 5th quintile group (HR 0.77 [95% CI 0.69, 0.85]) had a lower risk of type 2 diabetes before adjustment for BMI. There was an interaction between DII and BMI on type 2 diabetes risk (pInteraction < 0.0001). The overall association was partly mediated by BMI (58%). CONCLUSIONS/INTERPRETATION: Our findings suggest that a higher anti-inflammatory potential of the diet is associated with a lower risk of type 2 diabetes, and the association may be mediated by BMI. These results may improve our understanding of the mechanisms underlying the role of diet-related anti-inflammation in the pathogenesis of type 2 diabetes in women. Further studies are warranted to validate our results and evaluate whether the results are similar in men.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Inflamação , Idoso , Feminino , Humanos , Incidência , Estilo de Vida , Pessoa de Meia-Idade , Risco
11.
Clin Endocrinol (Oxf) ; 89(4): 514-525, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29935032

RESUMO

CONTEXT: Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied. DESIGN AND PARTICIPANTS: The Three-City cohort study included (1999-2001) 3650 men ≥65 years who were followed for mortality over 12 years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms. MAIN OUTCOME: Mortality data were obtained from death certificates. We used inverse probability weighted Cox models to examine the association of oestradiol with all-cause and cause-specific mortality and its interaction with ER genetic polymorphisms. RESULTS: A total of 183 men died over the follow-up (cardiovascular disease (CVD), n = 44; cancer, n = 57; other causes, n = 82). After adjustment, there was a quadratic relationship of all-cause mortality with tE2 and fE2 (P-quadratic = 0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P-quadratic = 0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all-cause mortality. CONCLUSION: In elderly men, we showed a nonlinear association of tE2 and fE2 with all-cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association.


Assuntos
Estradiol/sangue , Receptores Estrogênicos/genética , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/mortalidade , Polimorfismo Genético/genética , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto Jovem
12.
J Endocr Soc ; 2(4): 322-335, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29577108

RESUMO

Previous studies have shown controversial results about the role of testosterone in all-cause mortality in elderly men. We hypothesized that metabolic syndrome (MetS) could partly explain this discrepancy. We therefore examined the association of all-cause mortality with total and bioavailable testosterone, taking into account the MetS. We used data from the Three-City Cohort (3C) study with 12-year follow-up. The 3C study included 3650 men aged >65 years in three French cities. Hormone was measured in a random subsample of 444 men, and MetS was determined as stated by the International Diabetes Federation criteria. We used inverse-probability-weighted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Of 444 men included in the analysis, 106 (23.9%) had MetS at baseline, and 166 died over the follow-up. There was a significant interaction between testosterone level and MetS for all-cause mortality (P = 0.002 and P = 0.008 for total and bioavailable testosterone, respectively). Among men with MetS, a decrease in one standard deviation of testosterone was associated with higher mortality risk [HR 1.78 (95% CI 1.13 to 2.78) and HR 1.83 (95% CI 1.17 to 2.86) for total and bioavailable testosterone, respectively]. By contrast, there was no association of testosterone with mortality risk among men without MetS. Our results suggest that MetS modifies the association between testosterone and mortality in older men. If confirmed, these findings could contribute to improve risk stratification and better manage the health of older men.

13.
Scand J Work Environ Health ; 44(3): 310-322, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29405242

RESUMO

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.


Assuntos
Neoplasias da Mama Masculina/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Solventes/toxicidade , Adulto , Idoso , Benzeno/toxicidade , Neoplasias da Mama Masculina/epidemiologia , Estudos de Casos e Controles , Etilenoglicol/toxicidade , Europa (Continente)/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Tricloroetileno/toxicidade
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