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The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell's C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations., (© 2024. The Author(s).)

Background: Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality., Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35-70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years)., Results: After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI., Conclusions: Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death., (© 2024. World Health Organization.)

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk., (© 2023. Springer Nature B.V.)

Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons., Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (-0.53 kg/5 years; 95% confidence interval [CI]: -0.99, -0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction., Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly)phenol biomarkers are needed to confirm these suggestive protective trends., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Dioxins and polychlorinated biphenyls (PCBs) are toxic, endocrine disruptors and persistent chemicals for which the main exposure source is diet due to their bioaccumulation and biomagnification in food chains. Cohort studies in the general populations have reported inconsistent associations between these chemicals in serum/plasma and mortality. Our objective was to study the association between dietary intake of 17 dioxins and 35 PCBs and all-cause, cancer-specific and cardiovascular-specific mortalities were assessed in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with European food contamination data provided by the European Food Safety Authority. We applied multivariable Cox regressions. The analysis included 451,390 adults (mean ± SD age:51.1 ± 9.7 years) with 46,627 deaths and a median follow-up of 17.4 years (IQR = 15.2-19.1). A U-shaped non-linear association with all-cause mortality for dietary intake of dioxins (P non-linearity <0.0001), DL-PCB (P non-linearity  = 0.0001), and NDL-PCBs (P non-linearity <0.01) was observed. For example, the hazard ratios (95%Confidance interval) for all-cause mortality obtained with the spline model was equal to 1.03 (1.02-1.05) for low levels of intake to dioxins (7 pg TEQ/day), 0.93 (0.90-0.96) for moderate levels of intake (25 pg TEQ/day), while for high levels of intake (55 pg TEQ/day) it was 1.03 (0.97-1.09). Intake of dioxins, DL-PCBs and NDL-PCBs was not associated with cardiovascular mortality. There was no association between intakes of dioxins and cancer mortality, but a U-shaped association was observed for intake of DL-PCBs and intakes of NDL-PCBs and cancer mortality. The PCBs and dioxins are known to have endocrine disrupting properties which can lead to non-monotonic dose responses. These results need to be interpreted with caution and further studies are needed to better clarify the association between dietary intake of dioxins and PCB and mortality in the general population., 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 © 2023 Elsevier GmbH. All rights reserved.)

Background: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer., Methods: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI)., Results: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m 2 ) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m 2 ) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47)., Conclusions: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population., (© 2023. The Author(s).)

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-DII r ), 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-DII r 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., Competing Interests: Conflicts of Interest Dr. James R. Hébert owns controlling interest in Connecting Health Innovations LLC (CHI), a company that has licensed the right to his invention of the dietary inflammatory index (DII®) from the University of South Carolina in order to develop computer and smartphone applications for patient counseling and dietary intervention in clinical settings. Dr. Nitin Shivappa is an employee of CHI. The subject matter of this paper will not have any direct bearing on that work, nor has CHI-related activity exerted any influence on this project., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5 years., Methods: A total of 349,165 men and women aged 25 to 70 years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries. Body weight was measured at baseline and at follow-up after a median time of 5 years. Polyphenol intake, including four main polyphenol classes and eighteen subclasses, was estimated using validated dietary questionnaires and Phenol-Explorer. Multilevel mixed linear regression models were used to estimate the associations., Results: Participants gained, on average, 2.6 kg (±5.0 kg) over 5 years. Total flavonoids intake was inversely associated with body weight change (-0.195 kg/5 years, 95% CI: -0.262 to -0.128). However, the intake of total polyphenols (0.205 kg/5 years, 95% CI: 0.138 to 0.272) and intake of hydroxycinnamic acids (0.324 kg/5 years, 95% CI: 0.267 to 0.381) were positively associated with body weight gain. In analyses stratified by coffee consumption, hydroxycinnamic acid intake was positively associated with body weight gain in coffee consumers (0.379 kg/5 years, 95% CI: 0.319 to 0.440), but not in coffee nonconsumers (-0.179 kg/5 years, 95% CI: -0.490 to 0.133)., Conclusions: Higher intakes of flavonoids and their subclasses are inversely associated with a modest body weight change. Results regarding hydroxycinnamic acids in coffee consumers require further investigation., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI., (© World Health Organization, 2022. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

Epidemiologic studies have indicated that cruciferous vegetables can influence the cancer risk; therefore, we examined with a cross-sectional approach the correlation between the frequent consumption of the total cruciferous vegetables and the formation of bulky DNA damage, a biomarker of carcinogen exposure and cancer risk, in the Gen-Air study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. DNA damage measurements were performed in the peripheral blood of 696 of those apparently healthy without cancer controls, including 379 never-smokers and 317 former smokers from seven European countries by the 32P-postlabeling assay. In the Gen-Air controls, the median intake of cruciferous vegetables was 6.16 (IQR 1.16−13.66) g/day, ranging from 0.37 (IQR 0−6.00) g/day in Spain to 11.34 (IQR 6.02−16.07) g/day in the UK. Based on this information, participants were grouped into: (a) high consumers (>20 g/day), (b) medium consumers (3−20 g/day) and (c) low consumers (<3.0 g/day). Overall, low cruciferous vegetable intake was correlated with a greater frequency of bulky DNA lesions, including benzo(a)pyrene, lactone and quinone-adducts and bulky oxidative lesions, in the adjusted models. Conversely, a high versus low intake of cruciferous vegetables was associated with a reduction in DNA damage (up to a 23% change, p = 0.032); this was particularly evident in former smokers (up to a 40% change, p = 0.008). The Generalized Linear Regression models indicated an overall Mean Ratio between the high and the low consumers of 0.78 (95% confidence interval, 0.64−0.97). The current study suggests that a higher intake of cruciferous vegetables is associated with a lower level of bulky DNA adducts and supports the potential for cancer prevention strategies through dietary habit changes aimed at increasing the consumption of cruciferous vegetables.

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes., Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality., Design, Setting, and Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020., Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination., Main Outcomes and Measures: The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors., Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality., Conclusion and Relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health., Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics., Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP., Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers., Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Vitamin D deficiency is associated with higher all-cause mortality, but associations with specific causes of death are unclear. We investigated the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and cause-specific mortality using a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS). Eligibility for the case-cohort study was restricted to participants with baseline dried blood spot samples and no pre-baseline diagnosis of cancer. These analyses included participants who died (n = 2307) during a mean follow-up of 14 years and a sex-stratified random sample of eligible cohort participants ('subcohort', n = 2923). Concentration of 25(OH)D was measured using liquid chromatography-tandem mass spectrometry. Cox regression, with Barlow weights and robust standard errors to account for the case-cohort design, was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cause-specific mortality in relation to 25(OH)D concentration with adjustment for confounders. Circulating 25(OH)D concentration was inversely associated with risk of death due to cancer (HR per 25 nmol/L increment = 0.88, 95 % CI 0.78-0.99), particularly colorectal cancer (HR = 0.75, 95 % CI 0.57-0.99). Higher 25(OH)D concentrations were also associated with a lower risk of death due to diseases of the respiratory system (HR = 0.62, 95 % CI 0.43-0.88), particularly chronic obstructive pulmonary disease (HR = 0.53, 95 % CI 0.30-0.94), and diseases of the digestive system (HR = 0.44, 95 % CI 0.26-0.76). Estimates for diabetes mortality (HR = 0.64, 95 % CI 0.33-1.26) and cardiovascular disease mortality (HR = 0.90, 95 % CI 0.76-1.07) lacked precision. The findings suggest that vitamin D might be important for preventing death due to some cancers, respiratory diseases, and digestive diseases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)