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Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. Registry: The protocol is registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a single food history questionaire, and food substitutions were modelled using cox proportional hazard models. 95 % confidence intervals were generated via bootstrapping. 71 081 women free of diabetes and 45 771 women free of hypertension were followed for an average of 18·7 and 18·3 years, respectively. 2681 incident cases of diabetes and 12 327 incident cases of hypertension were identified. Relative to PRM, fatty fish was associated with a 15 % lower risk of diabetes (HR = 0·85, 95 CI (0·73, 0·97)) and hypertension (HR = 0 85 (0·79, 0·91)). Between 3 and 10 % lower risk of hypertension or diabetes was also observed when comparing PRM with vegetables, unprocessed red meat or pulses. Relative to PRM, alternative protein sources such as fatty fish, unprocessed red meat, vegetables or pulses was associated with a lower risk of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Purpose: The impact of a healthy diet on asthma prevention and management, particularly among elderly women, remains poorly understood. We investigated whether a healthy diet would be associated with fewer asthma symptoms, and, among women with asthma, with reduced uncontrolled asthma and metabolic-related multimorbidity. Methods: We included 12,991 elderly women (mean age = 63 years) from the Asthma-E3N study, a nested case–control study within the French E3N cohort. Negative binomial regressions were used to analyse associations between a healthy diet [evaluated by the Alternate Healthy Eating Index-2010 (AHEI-2010)] and a validated asthma symptom score, and logistic regressions to analyse associations between the AHEI-2010 with the asthma control test and multimorbidity profiles previously identified by clustering methods on medications used. Results: After adjustment for potential confounders, a linear inverse association was found between the AHEI-2010 score and the asthma symptom score [mean score ratio (95% CI) = 0.82 (0.75–0.90) for the highest versus lowest quintile; p for trend < 0.0001]. In addition, women in the highest versus lowest AHEI-2010 tertile were at a lower risk to belong to the "Predominantly metabolic multimorbidity-related medications profile" compared to the "Few multimorbidity-related medications" profile [OR 0.80 (0.63–1.00) for tertile 3; p for trend = 0.05; n = 3474]. Conclusion: Our results show that a healthy dietary intake could play an important role in the prevention and management of asthma over the life course. [ABSTRACT FROM AUTHOR]

Purpose: Thyroid cancer is the most common endocrine cancer and its etiology is still not well understood. The aim of the present study was to assess the association between an adapted dietary inflammatory index and differentiated thyroid cancer (DTC) risk in two population-based case–control studies (CATHY and YOUNG-THYR) conducted in France. Methods: These studies included a total of 1321 DTC cases and 1502 controls, for which an adapted dietary inflammatory index (ADII) was computed based on food frequency questionnaires in each study separately. The association between ADII and thyroid cancer risk was assessed using logistic regression models controlling for potential confounders. Results: Higher ADII scores, corresponding to a higher pro-inflammatory potential of the diet, were associated with higher DTC risk (odds ratio (OR) for 1 standard deviation (SD) increase: 1.09, 95% confidence interval (CI): 1.01, 1.18, P: 0.03). Associations were stronger in analyses restricted to women (OR for 1-SD increase: 1.14, 95% CI 1.04, 1.25, P: 0.005), as well as in women with lower education level, current smoking, or high body mass index. Conclusion: Our study suggests that a pro-inflammatory diet is associated with an increased risk of DTC, especially when combined with other inflammatory conditions such as tobacco smoking or overweight. Our findings will help better understand the role of diet-induced inflammation in DTC etiology. [ABSTRACT FROM AUTHOR]

Previous studies showed positive associations between milk intake and Parkinson's disease (PD) in men but not in women, but few studies were available in women. Due to the long prodromal PD phase, reverse causation represents a major threat to investigations of diet in PD; cohort studies with a long follow-up are needed. We investigated associations between intake of milk and other dairy products with PD incidence in women from the E3N cohort study (1993-2018). PD diagnoses were validated using medical records and drug claim databases. Diet was assessed via a dietary questionnaire. Hazard ratios (HR) were estimated using multivariable Cox regression models. Exposures were lagged by 5y in main analyses and longer lags in sensitivity analyses. We examined the impact of adjustment for premotor symptoms (constipation/depression). During a mean follow-up of 18.8y, 845 of 71,542 women developed PD. Main analyses showed a J-shaped association between total milk intake and PD (P-non linearity = 0.045), with a significant linear positive association among drinkers (HR/1-SD = 1.09, 95% CI = 1.01-1.18, P = 0.024), that was explained in secondary analyses by a different pattern of association for plain milk (alone or with cereals) and milk added to drinks (tea/coffee/chicory). PD incidence increased significantly with plain milk consumption (HR/1-SD = 1.08 [1.02-1.14], P = 0.014). A U-shaped relation was observed for milk added to drinks (P-non linearity = 0.038), with lower PD incidence in women with moderate consumption (HR = 0.77 [0.61-0.97], P = 0.030) and no difference between non-drinkers and those with the highest consumption (HR = 0.98 [0.79-1.21], P = 0.848). Findings were similar in analyses using longer lags and adjusted for constipation/depression. Consumption of other dairy products was not associated with PD. A J-shaped association between total milk intake and PD was explained by a different pattern of association for plain milk intake and milk added to drinks. Reverse causation is unlikely to explain a positive association of plain milk with PD incidence in women. The U-shaped relation for milk added to drinks could be explained by an interaction between milk and coffee/tea/chicory. Further studies are warranted to elucidate the underlying mechanisms., (© 2024. Springer Nature B.V.)

Objective: Obesity and type 2 diabetes (T2D) have been associated with low adherence to the 2017 French food-based dietary guidelines, as assessed by the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2). Whether the association between T2D and PNNS-GS2 is direct or mediated by obesity has been little investigated., Research Methods: The study included 71,450 women from the E3N-EPIC cohort, mean age of 52.9 y (SD 6.7). The simplified PNNS-GS2 was derived via food history questionnaire. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D. Causal mediation analyses were used to decompose the total effect of sPNNS-GS2 on T2D into a direct effect and indirect effect mediated by body mass index (BMI) or the waist-hip ratio (WHR)., Results: During a mean follow-up of 19 y, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D (P-nonlinearity = 0.92). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a lower T2D risk [HR (95% CI), 0.92 (0.89, 0.95)]. The overall associations were mainly explained by sPNNS-GS2-associated excess weight, with BMI and WHR mediating 52% and 58% of the associations, respectively., Conclusions: Higher adherence to French food-based dietary guidelines was associated with a lower risk of T2D in women, and a significant portion of this effect could be attributed to excess weight measured by BMI or WHR. This finding helps better understand the mechanisms underlying the diet-T2D association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dietary regimens promoting inflammatory conditions have been implicated in breast cancer development, but studies on the association between pro-inflammatory diet and breast cancer risk have reported inconsistent results. We investigated the association between the inflammatory potential of diet and breast cancer risk in a case-control study in France including 872 breast cancer cases and 966 population controls. All women completed a food frequency questionnaire that was used to compute a Dietary Inflammatory Index (DII) based on the inflammatory weight of 33 dietary components. The DII ranged from a median of - 3.22 in the lowest quartile (anti-inflammatory) to + 2.96 in the highest quartile (pro-inflammatory). The odds ratio contrasting quartile 4 to quartile 1 was 1.31 (95% CI 1.00, 1.73; p-trend = 0.02). Slightly higher odds ratios were observed in post-menopausal women, particularly those with body mass index > 25 kg/m 2 (odds ratio 1.62; 95% CI 0.92, 2.83; p-trend = 0.02), and among ever smokers (odds ratio 1.71; 95% CI 1.11, 2.65; p-trend 0.01). The analyses by breast cancer subtype showed that the DII was associated with breast tumors that expressed either the estrogen (ER) or progesterone (PR) hormone receptors or the Human Epidermal Growth Factor Receptor-2 (HER2), but no association was seen for the triple negative breast tumor subtype. Our results add further evidence that a pro-inflammatory diet is associated with breast cancer risk with possible effect variation according to tumor subtype., (© 2021. The Author(s).)

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.

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) (HR Quartile 1-Quartile 4 , 0.89; 95% CI, 0.79-0.99). An inverse relationship was observed between sports (HR sports >2 hours , 0.87; 95% CI, 0.83-0.93), walking (HR walk >6.5 hours , 0.94; 95% CI, 0.90-1.00), and gardening (HR gardening >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.

Objectives: Previous studies have reported controversial findings regarding the association of testosterone with mortality in older men. This heterogeneity might be partially explained by comorbidities and the presence of metabolic syndrome, as well as differential associations according to causes of death., Methods: We used data from a random subsample of the Three-City study, in which hormone levels were measured in 338 men ≥65 years without metabolic syndrome who were followed-up for 12 years. Vital status was determined for all participants from different sources. We used inverse-probability-weighted Cox regression to estimate the hazard ratios (HRs) of cause-specific mortality and 95% confidence intervals (CIs)., Results: Over the follow-up period, 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 levels were associated with increased cardiovascular mortality (HR for 1-standard deviation increase, 1.86; 95% CI, 1.28 to 2.71 and 1.50; 95% CI, 1.04 to 2.17 for total and bioavailable testosterone, respectively). By contrast, there were no significant associations of testosterone with mortality from cancer and other causes., Conclusions: 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 partially explain the heterogeneity across studies on the relationship between testosterone levels and mortality.