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The role of dietary macronutrients and energy intake in the aging process has been well‐established. However, previous research has mainly focused on the association between leukocyte telomere length (LTL) and individual macronutrients, while the effects of macronutrient composition on LTL remain unclear. This cross‐sectional analysis involved 4130 US adults (44.8 ± 17.0 years; 51% female) from the National Health and Nutrition Examination Survey during 1999–2002. A single 24‐h dietary recall is used to collect dietary data. The relationship between dietary macronutrient composition and LTL is examined using three‐dimensional generalized additive models. After adjustment for age, sex, ethnicity, education, physical activity, BMI, and dietary quality, a three‐dimensional association of macronutrient composition with LTL (P = 0.02) is revealed. Diets lower in protein (5–10%), higher in carbohydrates (75%), and lower in fat (15–20%) are associated with the longest LTL corresponding to 7.7 years of slower biological aging. Diets lowest in protein (5%) and carbohydrate (40%), while highest in dietary fat (55%) are associated with the shortest LTL, corresponding to accelerated biological aging of 4.4 years. The associations appeared magnified with higher energy intake. These findings support a complex relationship between dietary macronutrients and biological aging independent of diet quality. [ABSTRACT FROM AUTHOR]

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)D.sub.3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D.sub.3) 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)D.sub.3 (N = 40,562), and C3-epi-25(OH)D.sub.3 (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)D.sub.3 and 3 loci associated with C3-epi-25(OH)D.sub.3 . 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)D.sub.3 (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)D.sub.3 (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)D.sub.3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D.sub.3 (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., Author(s): Ju-Sheng Zheng 1,2,*, Jian'an Luan 1, Eleni Sofianopoulou 3,4, Stephen J. Sharp 1, Felix R. Day 1, Fumiaki Imamura 1, Thomas E. Gundersen 5, Luca A. Lotta 1, Ivonne [...]

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]

Glyceraldehyde‐derived advanced glycation end products (glycer‐AGEs) could contribute to colorectal cancer development and progression due to their pro‐oxidative and pro‐inflammatory properties. However, the association of glycer‐AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer‐AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer‐AGEs concentrations with CRC‐specific and all‐cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow‐up, 529 participants died (409 from CRC). Glycer‐AGEs were statistically significantly positively associated with CRC‐specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04‐2.25, Ptrend =.002) and all‐cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16‐2.26, Ptrend <.001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer‐AGEs and CRC‐specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74‐1.42; HRdistal colon = 1.51, 95% CI: 1.20‐1.91; Peffect modification =.02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer‐AGEs category relative to lowest BMI and glycer‐AGEs category for both CRC‐specific (HR = 1.78, 95% CI: 1.02‐3.01) and all‐cause mortality (HR = 2.15, 95% CI: 1.33‐3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer‐AGEs are positively associated with CRC‐specific and all‐cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted. [ABSTRACT FROM AUTHOR]

The gut microbiome has been shown to play a role in the relationship between diet and cardiometabolic health. We sought to examine the degree to which key microbial lignan metabolites are involved in the relationship between diet quality and cardiometabolic health using a multidimensional framework. This analysis was undertaken using cross-sectional data from 4685 US adults (age 43.6 ± 16.5 years; 50.4% female) participating in the National Health and Nutrition Examination Survey for 1999–2010. Dietary data were collected from one to two separate 24-hour dietary recalls and diet quality was characterized using the 2015 Healthy Eating Index. Cardiometabolic health markers included blood lipid profile, glycemic control, adiposity, and blood pressure. Microbial lignan metabolites considered were urinary concentrations of enterolignans, including enterolactone and enterodiol, with higher levels indicating a healthier gut microbial environment. Models were visually examined using a multidimensional approach and statistically analyzed using three-dimensional generalized additive models. There was a significant interactive association between diet quality and microbial lignan metabolites for triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, insulin, oral glucose tolerance, adiposity, systolic blood pressure, and diastolic blood pressure (all p < 0.05). Each of these cardiometabolic health markers displayed an association such that optimal cardiometabolic health was only observed in individuals with both high diet quality and elevated urinary enterolignans. When comparing effect sizes on the multidimensional response surfaces and model selection criteria, the strongest support for a potential moderating relationship of the gut microbiome was observed for fasting triglycerides and oral glucose tolerance. In this study, we revealed interactive associations of diet quality and microbial lignan metabolites with cardiometabolic health markers. These findings suggest that the overall association of diet quality on cardiometabolic health may be affected by the gut microbiome. [ABSTRACT FROM AUTHOR]

Using the parametric g-formula, we estimated the 27-year risk of all-cause and specific causes of mortality under different potential interventions for blood lead (BLLs) and urinary cadmium (UCd) levels. We used data on 14,311 adults aged ≥20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through 31 Dec 31 2015. Time and cause of death were determined from the National Death Index records. We used the parametric g-formula with pooled logistic regression models to estimate the relative and absolute risk of all-cause, cardiovascular, and cancer mortality under different potential threshold interventions for BLLs and UCd concentrations. Median follow-up was 22.5 years. A total of 5167 (36%) participants died by the end of the study, including 1550 from cardiovascular diseases and 1135 from cancer. Increases in BLLs and creatinine-corrected UCd levels from the 5th to the 95th percentiles were associated with risk differences of 4.17% (1.54 to 8.77) and 6.22% (4.51 to 12.00) for all-cause mortality, 1.52% (0.09 to 3.74) and 1.06% (−0.57 to 3.50) for cardiovascular disease mortality, and 1.32% (−0.09 to 3.67) and 0.64% (−0.98 to 2.80) for cancer mortality, respectively. Interventions to reduce historical exposures to lead and cadmium may have prevented premature deaths, especially from cardiovascular disease. [ABSTRACT FROM AUTHOR]

We aimed to test the hypothesis that adherence to a healthful plant-based diet (hPDI) is associated with a subsequent decrease in the incidence of asthma symptoms, with an opposite association with adherence to an unhealthful plant-based diet (uPDI). In addition, we evaluated a potential mediating role of body mass index (BMI) and the modifying effect of smoking. Among 5700 elderly women from the French Asthma-E3N study with dietary data in 1993 and 2005, we assessed the incidence of asthma symptoms in 2018 among women with no asthma symptoms in 2011. BMI was evaluated in 2008. Mediation analyses in the counterfactual framework were used to disentangle total, direct, and indirect effects mediated by BMI. We found that both healthful and unhealthful plant-based diets were associated with a lower incidence of asthma symptoms over time, mediated by BMI (OR (95%CI) for the indirect effect: 0.94 (0.89–1.00) for hPDI and 0.92 (0.70–1.00) for uPDI)). Associations with both healthful and unhealthful PDIs were mediated by changes in BMI by 33% and 89%, respectively. Plant-based diets (healthful and unhealthful) were associated with subsequently reduced incidences of asthma symptoms over time, partly or almost totally mediated by BMI according to their nutritional quality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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). 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. These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman's correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13–0.54, p < 0.05; and habitual rpartial = 0.14–0.28, p < 0.01), proanthocyanidins (acute rpartial = 0.24–0.49, p < 0.001; and habitual rpartial = 0.10–0.15, p < 0.05), theaflavins (acute rpartial = 0.22–0.31, p < 0.001; and habitual rpartial = 0.20–0.26, p < 0.01), and total flavan-3-ols (acute rpartial = 0.40–0.48, p < 0.001; and habitual rpartial = 0.23–0.33, p < 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12–0.30, p < 0.05) and habitual intake (rpartial = 0.10–0.27, p < 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Active smoking and the A blood group are associated with pancreatic adenocarcinoma (PC) risk. However, potential interactions between those risk factors and the role of passive smoking have been little investigated. We aimed to explore specific and joint associations of passive and active smoking, and effect modification by the ABO blood group in French women., Methods: The study included 96,594 women from the E3N prospective cohort, mean age: 49 years (SD 6.7). Information on active and passive smoking was reported at inclusion and throughout follow-up. Cases were classified according to the International Classification of Diseases 10. Associations with passive and active smoking and effect modification by the ABO blood group were investigated with multivariable Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Results: During a 24-year median follow-up, 346 incident PC cases were identified. Current smoking compared with never and former smoking (HR 1.51 [95% CI 1.08-2.10]), and passive smoking in childhood compared with no childhood exposure (HR 1.47 [95% CI 1.08-2.00]) were associated with increased PC risk, but not passive exposure in adulthood (HR 1.16 [95% CI 0.91-1.47]). Exposure to both passive smoking in childhood and current smoking was associated with a stronger risk (HR 2.80 [95% CI 1.42-5.52]) than exposure to both current smoking and passive smoking only in adulthood (HR 1.68 [95% CI 1.10-2.57]) compared with neither passive nor active smoking. Associations between active smoking and PC risk were strongest in the O or B groups, while associations with passive smoking were strongest in the A or AB blood groups, but the interaction terms were not statistically significant., Conclusions: Both current smoking and passive smoking in childhood were associated with PC risk, with a maximal risk of current smokers exposed to passive smoking during childhood. Possible interactions between blood groups and active or passive smoking must be investigated in a larger series., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI., Materials and Methods: We designed an online 27-question-based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings., Results: ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI., Conclusion: These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.

Introduction: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort., Methods: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI)., Results: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile., Discussion: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Epidemiological studies assessing the influence of vegetarian diets on breast cancer (BC) risk have produced inconsistent results. Few studies have assessed how the incremental decrease in animal foods and the quality of plant foods are linked with BC., Objectives: Disentangle the influence of plant-based diet quality on BC risk between postmenopausal females., Methods: Total of 65,574 participants from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort were followed from 1993-2014. Incident BC cases were confirmed through pathological reports and classified into subtypes. Cumulative average scores for healthful (hPDI) and unhealthful (uPDI) plant-based diet indices were developed using self-reported dietary intakes at baseline (1993) and follow-up (2005) and divided into quintiles. Cox proportional hazards models were used to estimate adjusted HR and 95% CI., Results: During a mean follow-up of 21 y, 3968 incident postmenopausal BC cases were identified. There was a nonlinear association between adherence to hPDI and BC risk (P nonlinear < 0.01). Compared to participants with low adherence to hPDI, those with high adherence had a lower BC risk [HR Q3 compared with Q1 (95% CI): 0.79 (0.71, 0.87) and HR Q4 compared with Q1 (95% CI): 0.78 (0.70, 0.86)]. In contrast, higher adherence to unhealthful was associated with a linear increase in BC risk [P nonlinear = 0.18; HR Q5 compared with Q1 (95% CI): 1.20 (1.08, 1.33); P trend < 0.01]. Associations were similar according to BC subtypes (P heterogeneity > 0.05 for all)., Conclusions: Long-term adherence to healthful plant foods with some intake of unhealthy plant and animal foods may reduce BC risk with an optimal risk reduction in the moderate intake range. Adherence to an unhealthful plant-based diet may increase BC risk. These results emphasize the importance of the quality of plant foods for cancer prevention. This trial was registered at clinicaltrials.gov (NCT03285230)., (Copyright © 2022. Published by Elsevier Inc.)

We aimed to test the hypothesis that adherence to a healthful plant-based diet (hPDI) is associated with a subsequent decrease in the incidence of asthma symptoms, with an opposite association with adherence to an unhealthful plant-based diet (uPDI). In addition, we evaluated a potential mediating role of body mass index (BMI) and the modifying effect of smoking. Among 5700 elderly women from the French Asthma-E3N study with dietary data in 1993 and 2005, we assessed the incidence of asthma symptoms in 2018 among women with no asthma symptoms in 2011. BMI was evaluated in 2008. Mediation analyses in the counterfactual framework were used to disentangle total, direct, and indirect effects mediated by BMI. We found that both healthful and unhealthful plant-based diets were associated with a lower incidence of asthma symptoms over time, mediated by BMI (OR (95%CI) for the indirect effect: 0.94 (0.89-1.00) for hPDI and 0.92 (0.70-1.00) for uPDI)). Associations with both healthful and unhealthful PDIs were mediated by changes in BMI by 33% and 89%, respectively. Plant-based diets (healthful and unhealthful) were associated with subsequently reduced incidences of asthma symptoms over time, partly or almost totally mediated by BMI according to their nutritional quality.