Macronutrient composition of plant-based diets and breast cancer risk: the E3N prospective cohort study.

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.

The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults.

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.

Childhood and adulthood passive and active smoking, and the ABO group as risk factors for pancreatic cancer in women.

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.

Association between endometriosis and risk of type 2 diabetes: Results from the prospective E3N cohort.

OBJECTIVE: Several studies suggest an association between endometriosis and the risk of cardio-metabolic diseases. This study aimed to prospectively evaluate the association between history of endometriosis and incident type 2 diabetes. STUDY DESIGN: E3N is a prospective cohort of 98,995 French women aged 40-65 years at inclusion. Multivariable Cox regression models were used to estimate hazard ratios and 95 % confidence intervals for the association between endometriosis and incident type 2 diabetes. We evaluated effect modification by age, body mass index, infertility treatment, adherence to the Mediterranean diet, and menopausal status. RESULTS: Age at inclusion was 51 ± 6 years and there were 2672 incident cases of type 2 diabetes. A total of 4606 women reported surgically-confirmed endometriosis among 83,582 women with no history of diabetes at inclusion. Endometriosis was not associated with type 2 diabetes risk in a model adjusted for age, BMI, physical activity, smoking, education, age at menarche and oral contraceptive use (hazard ratio [HR] = 1.09; 95 % confidence interval [CI] = 0.92-1.29), neither after further adjustment for family history of diabetes, hypertension and menopausal status (HR = 0.97;95%CI = 0.80-1.16). The relationship did not differ by age at inclusion, BMI, infertility treatment, diet or menopausal status (p > 0.05). CONCLUSIONS: Surgically-confirmed endometriosis was not associated with the risk of type 2 diabetes in this large cohort, confirming that endometriosis is not a risk marker for type 2 diabetes.

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

Diet Quality, Microbial Lignan Metabolites, and Cardiometabolic Health among US Adults.

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.

Dietary Inflammatory Index and risk of breast cancer: evidence from a prospective cohort of 67,879 women followed for 20 years in France.

BACKGROUND: Inflammation is implicated in breast cancer development, and diet is one of the modifiable risk factors involved in the regulation of chronic inflammation. Previous studies on the association between breast cancer risk and Dietary Inflammatory Indexes (DII) derived from food frequency questionnaires and data on inflammatory potential of dietary components have reported inconsistent results. OBJECTIVE: To investigate the association between the DII and the risk of breast cancer using data from a large population-based cohort study. DESIGN: A total of 67,879 women from the E3N cohort were followed from 1993 to 2014. A total of 5686 breast cancer cases were diagnosed during the follow-up. The food frequency questionnaire administered at baseline in 1993 was used to calculate an adapted DII. Cox proportional hazard models using age as the time scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Spline regression was used to determine any dose-response relationship. We also evaluated effect modification by menopausal status, body mass index, smoking status and alcohol consumption. RESULTS: The median DII score of the study population was slightly pro-inflammatory (DII = + 0.39); ranged from - 4.68 in the lowest quintile to + 4.29 in the highest quintile. The HR increased linearly with the DII (HR per 1SD = 1.04 [95% CI: 1.01, 1.07]), and reached 1.13 [95% CI: 1.04, 1.23] in the 5th quintile group as compared to the first. A positive linear dose-response relationship was also observed when modeling DII with spline functions. Slightly higher HRs were observed in non-smokers (HR for 1-SD increase 1.06 [95% CI: 1.02, 1.10]; p trend = 0.001) and in low-alcohol consumers (≤ 1 glass/day) (HR for 1-SD increase 1.05 [95% CI: 1.01, 1.08]; p trend = 0.002). CONCLUSION: Our results suggest a positive association between DII and breast cancer risk. Consequently, the promotion of anti-inflammatory diet may contribute to breast cancer prevention.

Long-term adherence to healthful and unhealthful plant-based diets and breast cancer risk overall and by hormone receptor and histologic subtypes among postmenopausal females.

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 (Pnonlinear < 0.01). Compared to participants with low adherence to hPDI, those with high adherence had a lower BC risk [HRQ3 compared withQ1 (95% CI): 0.79 (0.71, 0.87) and HRQ4 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 [Pnonlinear = 0.18; HRQ5 compared with Q1 (95% CI): 1.20 (1.08, 1.33); Ptrend < 0.01]. Associations were similar according to BC subtypes (Pheterogeneity > 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).

Palaeolithic diet score and risk of breast cancer among postmenopausal women overall and by hormone receptor and histologic subtypes.

BACKGROUND: The Palaeolithic diet (PD) has gained popularity globally. There is emerging evidence of its putative health benefits as short-term effects on chronic diseases have been reported. We evaluated the association between long-term adherence to the PD and breast cancer (BC) risk among postmenopausal women. METHODS: 65,574 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort were followed from 1993 to 2014. Incident BC cases were identified and validated. The PD score was calculated using dietary intake self-reported at baseline (1993) and follow-up (2005) or baseline only if censored before follow-up. Multivariable Cox proportional hazards regression models were used to estimate BC hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over a mean follow-up of 20 years, 3968 incident BC cases occurred. An increase of 1 standard deviation in the PD score was associated with an 8% lower BC risk, fully-adjusted model: HR1-SD 0.92, 95% CI; 0.89, 0.95. Compared to women with low adherence to the PD, women with high adherence had a 17% lower BC risk, HRQ5 vs Q1 0.83, 95% CI; 0.75, 0.92, Ptrend < 0.01. When considering BC subtypes, we observed the same pattern of association (Pheterogeneity > 0.10 for all). CONCLUSIONS: High adherence to a PD characterised by fruit, vegetables, nuts, fish, and lean meat and limited in dairy, grains, legumes, refined sugar, and alcohol was associated with a lower BC risk. The lack of heterogeneity according to BC subtypes could indicate the involvement of non-hormonal mechanisms. The protocol is registered at clinicaltrials.gov as NCT03285230. REGISTRY: The protocol is registered at clinicaltrials.gov as NCT03285230.

Associations with Blood Lead and Urinary Cadmium Concentrations in Relation to Mortality in the US Population: A Causal Survival Analysis with G-Computation.

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.

Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients.

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.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

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.

Relative to processed red meat, alternative protein sources are associated with a lower risk of hypertension and diabetes in a prospective cohort of French women.

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.

Potential benefits of joint hypothetical interventions on diet, lead, and cadmium on mortality in US adults.

BACKGROUND: Previous studies reported associations between high blood lead levels (BLLs) and urinary cadmium (UCd) concentrations and all-cause and cause-specific mortality. It is hypothesized that these associations are mediated by inflammation; therefore, adherence to an anti-inflammatory diet may mitigate these effects. We sought to estimate the potential effects of joint hypothetical interventions on metals levels and adherence to an anti-inflammatory diet or fruits and vegetables (FV) intake on the expected mortality distributions. METHODS: We used data on 14,311 adults aged ≥ 20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through Dec 31, 2015. We estimated daily FV servings and adherence to the dietary inflammatory index at baseline using 24-hour dietary recalls. Mortality was determined from the National Death Index records. We used the parametric g-formula with pooled logistic regression models to estimate the absolute risk of all-cause, cardiovascular, and cancer mortality under different hypothetical interventions compared to the natural course (no intervention). RESULTS: Overall, we observed a decreased mortality risk when intervening to lower metals levels or increasing adherence to an anti-inflammatory diet or the daily FV servings. The joint intervention to lower BLLs and UCd and increase the adherence to the anti-inflammatory diet had the strongest impact on cancer mortality risk (risk difference [RD] = -1.50% (-2.52% to -0.62%)) compared to the joint intervention only on metals levels RD= -0.97% (-1.89 to 0.70). The same pattern of associations was observed for the joint intervention to lower both metals and increased daily FV servings and cardiovascular diseases mortality risk. CONCLUSION: Higher diet quality may constitute a complementary approach to the interventions to reduce exposures to cadmium and lead to further minimize their effects on mortality. A paradigm shift is required from a pollutant-focused only to a combination with a human-focused approach for primary prevention against these metals.

Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. METHODS: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. RESULTS: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. CONCLUSIONS: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Adherence to mediterranean diet and the risk of differentiated thyroid cancer in a European cohort: The EPIC study.

Background: The Mediterranean diet (MD) has been proposed as a healthy diet with a potential to lower the incidence of several types of cancer, but there is no data regarding thyroid cancer (TC). We investigated the association between MD adherence, and its components, and the differentiated TC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Over 450,000 men and women from nine European countries were followed up for a mean of 14.1 years, during which 712 differentiated TC cases were identified. Adherence to MD was estimated using the relative MD (rMED) score, an 18-point scale including alcohol, and the adapted rMED (arMED) score, a 16-point scale excluding alcohol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Results: Adherence to the arMED score was not associated with the risk of differentiated TC (HRhigh vs. low adherence = 0.94, 95% CI: 0.70-1.25; p-trend 0.27), while a suggestive, but non-statistically significant inverse relationship was observed with rMED (HRhigh vs. low adherence = 0.88, 95% CI: 0.68-1.14; p-trend 0.17). Low meat (HRlow vs. high meat intake = 0.81, 95% CI: 0.67-0.99; p-trend = 0.04) and moderate alcohol (HRmoderate vs. non-moderate intake = 0.88, 95% CI: 0.75-1.03) intake were related with lower differentiated TC risk. Conclusions: Our study shows that a high adherence to MD is not strongly related to differentiated TC risk, although further research is required to confirm the impact of MD and, especially, meat intake in TC risk.

Inflammatory potential of the diet and association with risk of differentiated thyroid cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

PURPOSE: Chronic inflammation is thought to initiate or promote differentiated thyroid cancer (DTC) and previous studies have shown that diet can modulate this inflammatory process. We aimed to evaluate the association of several dietary scores reflecting the inflammatory potential of the diet with DTC risk. METHODS: Within the EPIC cohort, 450,063 participants were followed during a mean period of 14 years, and 712 newly incident DTC cases were identified. Associations between four dietary inflammatory scores [the dietary inflammatory index (DII®) and two energy-adjusted derivatives (the E-DIIr and the E-DIId), and the Inflammatory Score of the Diet (ISD)] and DTC risk were evaluated in the EPIC cohort using multivariable Cox regression models. RESULTS: Positive associations were observed between DTC risk and the DIIs (HR for 1 SD increase in DII: 1.11, 95%CI: 1.01, 1.23, similar results for its derivatives), but not with the ISD (HR for 1 SD increase: 1.04, 95% CI 0.93, 1.16). CONCLUSION: Diet-associated inflammation, as estimated by the DII and its derivatives, was weakly positively associated with DTC risk in a European adult population. These results suggesting that diet-associated inflammation acts in the etiology of DTC need to be validated in independent studies.

Association between blood metals mixtures concentrations and cognitive performance, and effect modification by diet in older US adults.

BACKGROUND: Chronic exposure to heavy metals has been associated with adverse neurological outcomes in older adults. Inflammatory processes are suspected as an underlying pathway by which metals exert their neurotoxicity. In parallel, a diet rich in antioxidant and anti-inflammatory components may protect against chronic inflammation. OBJECTIVES: We examined the associations of blood concentrations of lead, cadmium, and manganese as a mixture with cognitive performance in older US adults and potential modification of these associations by diet as measured by the Healthy Eating Index 2015 (HEI-2015) and the Adapted Dietary Inflammatory Index (ADII). METHODS: We used data on 1,777 adults ≥60 years old from the US National Health and Nutrition Examination Survey (NHANES; 2011-2014). We derived the ADII and the HEI-2015 from two nonconsecutive 24-hour diet recalls. Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, the animal fluency test, and the Digit Symbol Substitution Test (DSST). We also constructed a composite z-score reflecting overall cognitive performance. We used quantile g-computation to evaluate the joint associations of a mixture of metals with cognitive performance test scores. We also evaluated effect modification by sex and diet quality indices using Cochran Q tests. RESULTS: The median (interquartile range) of blood metals were 0.38 µg/L (0.35), 14.70 µg/L (11.70), and 8.74 µg/L (4.06) for cadmium, lead, and manganese, respectively. Increasing blood concentrations of all metals by one quartile was associated with a decrease in overall cognitive performance (-0.04; 95% confidence interval [CI] = -0.09, 0.02), CERAD (-0.04; 95% CI = -0.12, 0.03), animal fluency (-0.02; 95% CI, -0.11, 0.06), and DSST (-0.05; 95% CI = -0.11, 0.02) test scores. These associations were more pronounced in adults with high pro-inflammatory or low-diet quality and null or positive though imprecise associations in participants with a high anti-inflammatory. These associations also varied by sex with inverse associations in men and positive associations in women. CONCLUSIONS: Our findings suggest that adherence to an antioxidant and anti-inflammatory diet may prevent blood metals adverse cognitive effects among older adults. If confirmed, strategies based on diet could provide a potential complementary and efficient approach to counteract effects of environmental pollutants.

Healthy diet associated with better asthma outcomes in elderly women of the French Asthma-E3N study.

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.