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1.
Nutrients ; 13(9)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34579010

RESUMO

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

2.
Menopause ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34581294

RESUMO

OBJECTIVES: Although menopausal hormone therapy (MHT) remains the most effective treatment for vasomotor symptoms of menopause, its association with the development of arterial hypertension remains unclear. We sought to explore associations between different formulations of MHT and incident hypertension among menopausal women in a prospective cohort study. METHODS: We used the Etude Epidémiologique de femmes de la Mutuelle Générale de l'Education (E3N) cohort, a French prospective population-based study initiated in 1990 on 98,995 women. Out of these, 49,905 menopausal women with complete information on the use of MHT, and without prevalent hypertension at inclusion were included. RESULTS: The mean age of the population at baseline was 54.2 ±â€Š4.3 years, and 32,183 (64.5%) reported ever using MHT. Among these women, 10,173 cases of incident hypertension were identified over an average follow-up time of 10.6 years. Compared with women who never used MHT, those who ever used it had an increased risk of incident hypertension (adjusted HR 1.07, 95% CI 1.02-1.12) after adjustment for body mass index and other potential confounders. Oral but not transdermal estrogen use was associated with an increased risk of hypertension (adjusted HR = 1.09; 95% CI: 1.04-1.14 and HR = 1.03; 95% CI: 0.99-1.07, respectively). However, the HRs associated with oral and transdermal estrogens did not differ significantly (P-homogeneity = 0.09). Regarding the role of concomitant progestogens, pregnane and norpregnane derivatives were significantly associated with hypertension risk (HR = 1.12; 95% CI: 1.06-1.19 and HR = 1.06; 95% CI: 1.01-1.13, respectively). CONCLUSIONS: MHT was associated with a modest but significant increased risk of incident hypertension, especially when using oral estrogen in combination with a progestogen such as pregnane and norpregnane derivatives. Surveillance of blood pressure should be added to the medical surveillance of MHT users.Video Summary:http://links.lww.com/MENO/A802.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34548327

RESUMO

BACKGROUND: Evidence is accumulating that immune cells play a prominent role in pancreatic cancer aetiology but prospective investigations are missing. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sub-lineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. Odds ratios with 95% Confidence Intervals were estimated using logistic regressions, modelling relative counts of immune cells on a continuous scale. RESULTS: Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in sub-group analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. CONCLUSIONS: These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. IMPACT: We have shown, for the first time, that increased relative counts of regulatory T-cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development.

4.
BMJ ; 374: n1904, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470785

RESUMO

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Exposição Ambiental/efeitos adversos , Doenças não Transmissíveis/mortalidade , Europa (Continente) , Humanos
5.
Nutrients ; 13(8)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34444662

RESUMO

The serum copper (Cu) to zinc (Zn) ratio could be an important determinant of Type 2 diabetes (T2D) risk, but prospective epidemiological data are scarce. We aimed to investigate the association between T2D incidence and the dietary Cu/Zn ratio. A total of 70,991 women from the E3N cohort study were followed for 20 years. The intakes of copper and zinc were estimated at baseline using a validated food frequency questionnaire. We identified and validated 3292 incident T2D cases. Spline analysis showed that a Cu/Zn ratio < 0.55 was associated with a lower risk of T2D. Subgroup analyses comparing women in the highest versus the lowest quintile of Cu/Zn ratio showed the same pattern of association for obese women and those with zinc intake ≥8 mg/day. However, for women with zinc intake <8 mg/day, higher Cu/Zn ratio appeared to be associated with higher T2D risk. Our findings suggest that a lower dietary Cu/Zn ratio is associated with a lower T2D risk, especially among obese women and women with zinc intake >8 mg/day. Further studies are warranted to validate our results.


Assuntos
Cobre/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Obesidade/epidemiologia , Zinco/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , França/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
6.
Clin Nutr ; 40(9): 5079-5088, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34455267

RESUMO

BACKGROUND: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity. METHODS: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI). RESULTS: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline. CONCLUSIONS: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.

7.
Int J Cancer ; 149(11): 1887-1897, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34278567

RESUMO

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.

8.
J Nutr ; 151(9): 2731-2740, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34236437

RESUMO

BACKGROUND: Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored. OBJECTIVES: To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI. METHODS: The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored. RESULTS: There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively. CONCLUSIONS: Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230.

9.
Maturitas ; 150: 22-29, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34274072

RESUMO

OBJECTIVES: While it has been reported that women with uterine fibroids or endometriosis are commonly overweight and hypertensive, the association between non-malignant gynecological diseases and the risk of hypertension has been little studied prospectively. The aim of this study was to investigate in a large French cohort of women whether a history of hysterectomy, uterine fibroids, or endometriosis was prospectively related to an increased risk of incident hypertension. STUDY DESIGN: We analyzed 50,286 women from the E3N cohort who were free of hypertension at baseline, with a median follow-up of 16.4 years. MAIN OUTCOME MEASURES: Gynecological diseases were based on self-report. Cox proportional hazards models with age as the timescale were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Covariates included smoking status, body mass index (BMI), physical activity, and hormonal factors. RESULTS: A total of 12,073 women (24%) developed hypertension during follow-up. Women with a history of hysterectomy had an increased risk of incident hypertension, which persisted after adjustment for potential confounding factors (adjusted HR=1.18, 95% CI 1.12-1.24). Risk was similar in women with hysterectomy with or without oophorectomy. Risk of hypertension was higher in women with a history of endometriosis (HRendometriosis 1.19, 95%CI 1.11-1.22) or uterine fibroids (HRfibroids 1.18, 95%CI 1.13-1.22), irrespective of hysterectomy. Associations were similar after further adjustment for BMI. CONCLUSIONS: Hysterectomy and non-malignant gynecological diseases were associated with an increased risk of hypertension in this large prospective study. Women with these conditions may benefit from blood pressure monitoring. ClinicalTrials.gov identifier: NCT03285230.


Assuntos
Índice de Massa Corporal , Doenças dos Genitais Femininos/cirurgia , Hipertensão/etiologia , Histerectomia/efeitos adversos , Ovariectomia/efeitos adversos , Adulto , Idoso , Feminino , França/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
10.
Int J Epidemiol ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259837

RESUMO

BACKGROUND: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts. METHODS: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline. RESULTS: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, ß-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk. CONCLUSIONS: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.

11.
Eur Respir J ; 57(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34088754

RESUMO

BACKGROUND: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults. METHODS: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders. RESULTS: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 µg·m-3 for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 µg·m-3 for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5×10-5 m-1 for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold. CONCLUSIONS: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , Exposição Ambiental/análise , Europa (Continente) , Humanos , Incidência , Material Particulado/análise , Suécia
12.
BMC Oral Health ; 21(1): 315, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162373

RESUMO

BACKGROUND: Type 2 diabetes (T2D) has been identified as a risk factor for poor oral health, however, a limited number of oral health and T2D characteristics have been studied so far. We sought to assess T2D status, age at diagnosis, duration since diagnosis and treatment in relation to a variety of oral diseases. METHODS: Cross-sectional data were analyzed from the E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study which enrolled 60,590 women. Participants self-reported oral health status, and T2D cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases. Multivariable-adjusted ORs and 95% CIs were estimated using logistic regression models. RESULTS: The mean age (SD) of the women was 70 years (7.2), and 4.7% (n = 2857) had T2D. Compared to women without T2D, women with T2D were more likely to report a poor perceived oral health (OR 1.37 [95% CI 1.18, 1.60]), wearing dental prostheses (1.26 [1.14, 1.39]) and having problems of biting and chewing food (1.19 [1.07, 1.33]). In addition, for women with T2D the age at diagnosis (inversely) and the duration (positively) were associated with the likelihood to report poor oral health. CONCLUSIONS: For women with T2D, duration and age at diagnosis are associated with wearing prostheses, problems of biting and chewing, periodontitis and gingivitis.


Assuntos
Diabetes Mellitus Tipo 2 , Idoso , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Saúde Bucal , Fatores de Risco
13.
Cancer Med ; 10(13): 4604-4614, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34041857

RESUMO

This study aimed to evaluate the association between thyroid dysfunction and breast cancer risk. We included 239,436 females of the UK Biobank cohort. Information on thyroid dysfunction, personal and family medical history, medications, reproductive factors, lifestyle, and socioeconomic characteristics was retrieved from baseline self-reported data and hospital inpatient databases. Breast cancer diagnoses were identified through population-based registries. We computed Cox models to estimate hazard ratios (HRs) of breast cancer incidence for thyroid dysfunction diagnosis and treatments, and examined potential confounding and effect modification by comorbidities and breast cancer risk factors. In our study, 3,227 (1.3%) and 20,762 (8.7%) women had hyper- and hypothyroidism prior to the baseline. During a median follow-up of 7.1 years, 5,326 (2.2%) women developed breast cancer. Compared to no thyroid dysfunction, there was no association between hypothyroidism and breast cancer risk overall (HR = 0.93, 95% confidence interval (CI): 0.84-1.02, 442 cases), but we found a decreased risk more than 10 years after hypothyroidism diagnosis (HR=0.85, 95%CI 0.74-0.97, 226 cases). There was no association with hyperthyroidism overall (HR=1.08, 95%CI 0.86-1.35, 79 cases) but breast cancer risk was elevated among women with treated hyperthyroidism (HR=1.38, 95%CI: 1.03-1.86, 44 cases) or aged 60 years or more at hyperthyroidism diagnosis (HR=1.74, 95%CI: 1.01-3.00, 113 cases), and 5-10 years after hyperthyroidism diagnosis (HR=1.58, 95%CI: 1.06-2.33, 25 cases). In conclusion, breast cancer risk was reduced long after hypothyroidism diagnosis, but increased among women with treated hyperthyroidism. Future studies are needed to determine whether the higher breast cancer risk observed among treated hyperthyroidism could be explained by hyperthyroidism severity, type of treatment or aetiology.

14.
Sci Rep ; 11(1): 8932, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903625

RESUMO

Variants identified in earlier genome-wide association studies (GWAS) on differentiated thyroid carcinoma (DTC) explain about 10% of the overall estimated genetic contribution and could not provide complete insights into biological mechanisms involved in DTC susceptibility. Integrating systems biology information from model organisms, genome-wide expression data from tumor and matched normal tissue and GWAS data could help identifying DTC-associated genes, and pathways or functional networks in which they are involved. We performed data mining of GWAS data of the EPITHYR consortium (1551 cases and 1957 controls) using various pathways and protein-protein interaction (PPI) annotation databases and gene expression data from The Cancer Genome Atlas. We identified eight DTC-associated genes at known loci 2q35 (DIRC3), 8p12 (NRG1), 9q22 (FOXE1, TRMO, HEMGN, ANP32B, NANS) and 14q13 (MBIP). Using the EW_dmGWAS approach we found that gene networks related to glycogenolysis, glycogen metabolism, insulin metabolism and signal transduction pathways associated with muscle contraction were overrepresented with association signals (false discovery rate adjusted p-value < 0.05). Additionally, suggestive association of 21 KEGG and 75 REACTOME pathways with DTC indicate a link between DTC susceptibility and functions related to metabolism of cholesterol, amino sugar and nucleotide sugar metabolism, steroid biosynthesis, and downregulation of ERBB2 signaling pathways. Together, our results provide novel insights into biological mechanisms contributing to DTC risk.

15.
Gut Microbes ; 13(1): 1-14, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33874856

RESUMO

Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.

16.
Eur J Nutr ; 60(7): 3935-3945, 2021 Oct.
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.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Diabetes Mellitus Tipo 2/epidemiologia , Dieta , Feminino , Humanos , Hipertensão/epidemiologia , Estilo de Vida , Estudos Prospectivos , Fatores de Risco
17.
Neurology ; 97(1): e34-e41, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-33883242

RESUMO

OBJECTIVE: Migraine has been identified as a potential risk factor for hypertension in prospective studies. In women, migraine prevalence decreases after menopause, but no studies have determined whether migraine is associated with hypertension after menopause. This study sought to determine whether history of migraine was associated with an increased risk of hypertension among menopausal women. METHODS: We assessed associations between migraine and hypertension in a longitudinal cohort study of 56,202 menopausal women participating in the French E3N cohort, with follow-up beginning in 1993. We included women who did not have hypertension or cardiovascular disease at the time of menopause. Migraine was classified as ever or never at each questionnaire cycle. Cox proportional hazards models were used to investigate relations between migraine and hypertension, controlling for potential confounding. A secondary analysis with baseline in 2011 considered aura status, grouping participants reporting migraine as migraine with aura, migraine without aura, or unknown migraine type. RESULTS: During 826,419 person-years, 12,501 cases of incident hypertension were identified, including 3,100 among women with migraine and 9,401 among women without migraine. Migraine was associated with an increased risk of hypertension in menopausal women (hazard ratio [HR]migraine 1.29 [95% confidence interval 1.24, 1.35]) and was consistent in post hoc sensitivity analyses, such as when controlling for common migraine medications. Associations between migraine and hypertension were similar whether or not women reported aura (HRmigraine aura 1.54 [1.04, 2.30], HRmigraine no aura 1.32 [0.87, 2.02], p heterogeneity 0.60). Associations were slightly stronger among ever users of menopausal hormone therapy (HRmigraine 1.34 [1.27, 1.41]) than among never users (HRmigraine 1.19 [1.11, 1.28]). CONCLUSIONS: Migraine was associated with an increased risk of hypertension among menopausal women. In secondary analysis, we did not observe a significant difference between migraine with aura and migraine without aura.


Assuntos
Hipertensão/complicações , Transtornos de Enxaqueca/complicações , Pós-Menopausa , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Hipertensão/epidemiologia , Estilo de Vida , Estudos Longitudinais , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Enxaqueca com Aura/complicações , Enxaqueca com Aura/epidemiologia , Enxaqueca sem Aura/complicações , Enxaqueca sem Aura/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inquéritos e Questionários
18.
Oncotarget ; 12(5): 493-506, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33747362

RESUMO

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality. At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue. Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.

19.
Prev Med ; 150: 106485, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33647351

RESUMO

Studies have identified non-linear inverse relationships between physical activity and the risk of stroke. A U-shaped response has been observed between haemorrhagic stroke and physical activity. The objective of this study was to investigate the associations between physical activities on stroke. We used data from the E3N cohort study, a French prospective study of women initiated in 1990. From the women in the study, we included those without cardiovascular disease or cancer at baseline, resulting in 94,169 women. We assessed total physical activity in 1993, grouped as quartiles. Cox models adjusted for potential confounders were used to assess the relationship with stroke, considering cases until 2008. Splines were used to assess the shape of the response. Similarly, we then considered high and low-intensity physical activity grouped as tertiles. Among the included women, with a mean age of 51.2 ± 6.7 years, 592 cases of stroke were identified over an average follow-up time of 16.2 years. Total physical activity was associated with a lower stroke risk (HRQ1-Q4 = 0.38 [0.31, 0.49]). An inverse relationship was observed between physical activity and all stroke sub-types. A non-linear (L-shaped) relationship was observed for all-stroke, and ischemic stroke, and a U-shaped response for sub-arachnoid and intracerebral haemorrhage. High-intensity activities were associated with a U-shaped response for haemorrhagic stroke types. Low-intensity activities were associated with a linear response for all stroke types. Our results support other observations that physical activity may reduce stroke risk.


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Adulto , Estudos de Coortes , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
20.
Br J Cancer ; 124(10): 1734-1743, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33723391

RESUMO

BACKGROUND: Perturbations in circulating metabolites prior to a breast cancer diagnosis are not well characterised. We aimed to gain more detailed knowledge to help understand and prevent the disease. METHODS: Baseline plasma samples from 791 breast cancer cases and 791 matched controls from the E3N (EPIC-France) cohort were profiled by nuclear magnetic resonance (NMR)-based untargeted metabolomics. Partial least-squares discriminant analysis (PLS-DA) models were built from NMR profiles to predict disease outcome, and odds ratios and false discovery rate (FDR)-adjusted CIs were calculated for 43 identified metabolites by conditional logistic regression. RESULTS: Breast cancer onset was predicted in the premenopausal subgroup with modest accuracy (AUC 0.61, 95% CI: 0.49-0.73), and 10 metabolites associated with risk, particularly histidine (OR = 1.70 per SD increase, FDR-adjusted CI 1.19-2.41), N-acetyl glycoproteins (OR = 1.53, FDR-adjusted CI 1.18-1.97), glycerol (OR = 1.55, FDR-adjusted CI 1.11-2.18) and ethanol (OR = 1.44, FDR-adjusted CI 1.05-1.97). No predictive capacity or significant metabolites were found overall or for postmenopausal women. CONCLUSIONS: Perturbed metabolism compared to controls was observed in premenopausal but not postmenopausal cases. Histidine and NAC have known involvement in inflammatory pathways, and the robust association of ethanol with risk suggests the involvement of alcohol intake.

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