Elio Riboli

BackgroundThe association of fitness with cancer risk is not clear.MethodsWe used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method.ResultsAfter a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min−1⋅kg−1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73–0.89), colorectal (0.94, 0.90–0.99), and breast cancer (0.96, 0.92–0.99). In …

BackgroundA high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.MethodsWe examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata …

BackgroundUnderweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.MethodsWe used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and …

Background Obesity and diabetes are associated inversely with low‐grade prostate cancer risk and affect steroid hormone synthesis but whether they modify each other's impact on prostate cancer risk remains unknown. Methods We examined the independent associations of diabetes, body mass index (BMI), ‘a body shape index’ (ABSI), hip index (HI), circulating testosterone, sex hormone binding globulin (SHBG) (per one standard deviation increase) and oestradiol ≥175 pmol/L with total prostate cancer risk using multivariable Cox proportional hazards models for UK Biobank men. We evaluated multiplicative interactions (pMI) and additive interactions (relative excess risk from interaction (pRERI), attributable proportion (pAR), synergy index (pSI)) with obese (BMI ≥30 kg/m2) and diabetes. Results During a mean follow‐up of 10.3 years, 9417 incident prostate cancers were diagnosed in 195,813 men …

Association of atopic dermatitis with depression and sleep quality in an Asian general population cohort of 8887 participants Association of atopic dermatitis with depression and sleep quality in an Asian general population cohort of 8887 participants J Eur Acad Dermatol Venereol. 2024 Feb 19. doi: 10.1111/jdv.19836. Online ahead of print. Authors Yik Weng Yew 1 2 , Bill Rong Qin Chang 2 , Theresia Mina 2 , Elio Riboli 2 3 , Eng Sing Lee 2 4 , Joanne Ngeow 2 5 , Paul Elliott 2 3 , John C Chambers 2 3 , Jimmy Lee 2 6 , Marie Loh 1 2 3 7 Affiliations 1 National Skin Centre, Singapore City, Singapore. 2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore City, Singapore. 3 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. 4 Clinical Research Unit, National Healthcare Group Polyclinic, Singapore City, Singapore. 5 Division of …

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 …

High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002–0.067); p = 0.036) and “a body shape index” (ABSI; 0.039 (0.006–0.071); p = 0.021). There was …

Objectives We aimed to describe the trajectories of cognitive and physical symptoms before, during, and after a positive- or negative SARS-CoV-2 test and in untested controls. Design A prospective cohort study. Setting Norway, 27 March 2020 to 6 July 2022 Participants A total of 146 065 volunteers were recruited. Of these, 120 605 participants (mean age 49 (SD 13.7), 69% female), were initially untested for the SARS-CoV-2 virus, completed one or more follow-up questionnaires (response rates 72-90%) and were included for analysis. After 22 months of follow-up, 15 737 participants had a positive SARS-CoV-2 test, 67 305 a negative test, and 37 563 were still untested. Main outcome measures We assessed reported symptoms the past three weeks of memory or concentration problems, anosmia and dysgeusia, dyspnoea, fatigue, fever, headache, cough, muscular pain, nasal symptoms, sore throat and abdominal pain at baseline and through four follow-up questionnaires. In addition, overall health compared to a year before was measured with a five-point scale and memory problems were measured using the Everyday Memory Questionnaire-13 at two timepoints. The exposure, SARS-CoV-2 test status (positive, negative or untested), was obtained from a mandatory national registry or from self-report, and data were analysed using mixed model logistic regression. Results A positive SARS-CoV-2-test was associated with the following persistent symptoms, compared with participants with a negative test (1-3 months after a negative test); memory problems (3 to 6 months after a positive test: adjusted odds ratio (OR) 9.1, 95% confidence …

BackgroundTumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.MethodsWe meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10−8) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage …

Owing to shared risk factors between cardiometabolic diseases (CMDs) and cancer, coupled with population aging, the lifetime risk of an individual developing cancer after a CMD is increasing. Furthermore, biological mechanisms such as insulin resistance or inflammation may not only predispose individuals with CMD to an elevated risk of certain types of cancer but also to a diagnosis of cancer at an advanced stage [1, 2].Cancer stage at diagnosis strongly correlates with cancer survival rates and impacts treatment decisions. Early cancer detection is key to improving cancer outcomes, especially for cancers with poor prognosis. Factors associated with a higher risk of an advanced-stage diagnosis may differ from those associated with cancer incidence. Previous studies support an association between advanced-stage cancer at diagnosis and certain patient characteristics, such as higher body mass index (BMI), older age, smoking, comorbidities, and cancer type. Studies examining the influence of comorbidities on cancer stage at diagnosis have suggested that a CMD requiring regular medical follow-up is associated with earlier cancer detection [3, 4]. However, studies have also suggested that overall participation rates in cancer screening programs may be lower among individuals with type 2 diabetes (T2D) or cardiovascular diseases (CVD), which may lead to later cancer detection and a more advanced stage at diagnosis [5]. A better understanding of how CMDs prior to cancer are associated with stage at cancer diagnosis may inform cancer screening recommendations. This study aimed to investigate whether having a pre-existing CMD is …

Group meeting convened in 2014. 3 The expertise of the Advisory Group covered multiple disciplines, and the members appraised, on an individual nomination basis, the evidence according to human exposure (including any evidence of exposure in low-income and medium-income countries), cancer epidemiology, cancer bioassays in experimental animals, and carcinogen mechanisms, in line with the evaluation methodology recently refined in the Preamble to the IARC Monographs. 1 A complementary approach assessed all nominations using a chemoinformatics, text mining, and chemical similarity analysis workflow; 4 this approach helped to reveal coverage and gaps in the extent of evidence across data streams, supporting decisions on individual agents and groups of chemically related nominations. The Advisory Group deliberated on all nominated agents both by evidence stream (ie, exposure, human …

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 …

Dietary factors play a major role in cardiovascular diseases (CVDs), which are the leading cause of death worldwide. 1–3 Importantly, unhealthy diets, and in particular high sodium intake, are modifiable risk factors and can therefore be targeted for CVD prevention. 1, 3 The World Health Organization and European Society of Cardiology recommend diets rich in fruits and vegetables, wholegrains, legumes, nuts and fish, and low in salt, sugar, and saturated fat for prevention of CVD as well as other chronic diseases. 3, 4 Notably, limiting salt intake to< 5 g/day (equivalent to 2 g/day of sodium) is advised to lower blood pressure, while eliminating trans-fats and replacing saturated fat intake with monounsaturated or polyunsaturated fats will contribute to lowering circulating LDL cholesterol concentrations, which are two of the key risk factors for CVD. 1, 3 Consumption of predominantly plantbased diets tends to be …

Objectives: We aimed to examine associations between prediagnosis dietary patterns related to biological mechanisms underlying breast carcinogenesis, including inflammatory, insulin and estrogenic pathways, in relation to breast cancer (BC) survival.Methods: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and estrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adjusted Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality.Results: We included 13,270 BC cases with a mean follow-up of 8.6 years since diagnosis, with 2340 total deaths including 1475 from BC. High DRRD score was associated with lower risk of overall mortality (HRSD 0.92 95% CI 0.87–0.96); adherence to pro-inflammatory diets was borderline associated with 6% higher risk of mortality (95% CI 1.00–1.12). Women with antidiabetic and anti-inflammatory diets (high DRRD and low ISD) had 17% lower risk of overall mortality. No significant association with the ERDP was observed. No dietary pattern was associated with BC-specific mortality. Conclusions: Higher adherence to an anti-diabetic and antiinflammatory diet before diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta‐analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random‐effects meta‐analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all‐cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05‐1.10), breast cancer‐specific mortality (RR: 1.10, 95% CI: 1.06‐1.14) and second …

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel …

Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries particularly from Asia. Here, we present a WGS catalogue of 152,655 SVs from 8,392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which~ 75%(113,446 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 82,003 novel SVs that are specific to Asian populations. 38% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting ACMG-defined clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research.

Background There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Methods Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using …

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being 1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from...

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre- and postdiagnosis and overall mortality and BC-specific mortality among BC survivors. Our study included 13,624 BC survivors from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, with a mean follow-up of 8.6 years after diagnosis. Anthropometric data were obtained at recruitment for all cases and at a second assessment during follow-up for a subsample. We measured general obesity using the body mass index (BMI), whereas waist circumference and A Body Shape Index were used as measures of abdominal obesity. The annual weight change was calculated for cases with two …

Objectives: To investigate whether adherence to Mediterranean diet (MD) before a breast cancer (BC) diagnosis is associated with overall and BC-specific mortality. Methods: Our population included 13,270 incident BC cases from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to MD was estimated by means of the adapted relative Mediterranean diet (arMED), a 16-point score including 8 key components of MD that excludes alcohol. Multivariable Cox regression models were used to investigate the association between arMED and all-cause and BC-specific mortality by 3 categories of adherence to the score (low, medium, high) and by 3-unit increase in the score. Results: After a mean follow-up of 8.6 years since diagnosis, 2340 women died, 1475 of them from BC. Compared to medium adherence, low arMED, representing low adherence to MD, was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95% CI 1.01–1.26) and high arMED showed no statistically significant association with all-cause mortality (HR 0.94, 95% CI 0.84–1.05). A 3-unit increase in arMED score was associated with 8% lower risk of all-cause mortality (HR 0.92, 95% CI 0.87–0.97) and this result was sustained when restricted to postmenopausal women. The arMED score was not associated to BC-specific mortality.Conclusions: Following a Mediterranean diet before a breast cancer diagnosis may be a beneficial lifestyle choice to improve the prognosis of breast cancer survivors, particularly among postmenopausal women.

INTRODUCTION Metformin has been suggested as a therapeutic agent for dementia, but the relevant evidence has been partial and inconsistent. METHODS We established a national cohort of 210,237 type 2 diabetes patients in the UK Clinical Practice Research Datalink. Risks of incident dementia were compared between metformin initiators and those who were not prescribed any anti‐diabetes medication during follow‐up. RESULTS Compared with metformin initiators (n = 114,628), patients who received no anti‐diabetes medication (n = 95,609) had lower HbA1c and better cardiovascular health at baseline. Both Cox regression and propensity score weighting analysis showed metformin initiators had lower risk of dementia compared to those non‐users (adjusted hazard ratio = 0.88 [95% confidence interval: 0.84–0.92] and 0.90 [0.84–0.96]). Patients on long‐term metformin treatment had an even lower …

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited‐suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist‐hip‐ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random‐effects meta‐analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre‐defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all‐cause mortality (64 studies, 32 507 deaths), breast cancer‐specific mortality (39 studies, 14 106 deaths …

BackgroundObesity is associated with type 2 diabetes mellitus and chronic low-grade inflammation. Although chronic inflammatory conditions and diabetes are associated with anaemia, less is known about associations of obesity and body shape, independent of each other, with erythrocyte and reticulocyte parameters.MethodsWe investigated the associations of body mass index (BMI) and the allometric body shape index (ABSI) and hip index (HI), which are uncorrelated with BMI, with erythrocyte and reticulocyte parameters (all continuous, on a standard deviation (SD) scale) in UK Biobank participants without known metabolic, endocrine, or major inflammatory conditions (glycated haemoglobin HbA1c < 48 mmol/mol, C-reactive protein CRP < 10 mg/L). We examined erythrocyte count, total reticulocyte count and percent, immature reticulocyte count and fraction (IRF), haemoglobin, haematocrit, mean …

Background Diet has a direct impact on our health and as such is an important leverage in public health prevention strategies. Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label based on a nutrient profile called FSAm-NPS that was proposed as a tool to help people choose healthier foods. It has been adopted by several European countries, but remains optional under current EU labeling regulation (under revision). This study aimed to provide insights into the relevance of the FSAm-NPS to characterize healthier foods by studying associations with a range of biomarkers reflecting pathways underlying nutrition-health associations. Methods This analysis included healthy participants from the EPIC cohort study (inclusion in 1992-2000, 8 European countries) for which blood biomarkers were measured from baseline samples in several case-control studies …

BackgroundObesity is accompanied by low-grade inflammation and leucocytosis and increases the risk of venous thromboembolism. Associations with platelet count, however, are unclear, because several studies have reported positive associations only in women. Associations with body shape are also unclear, because waist and hip circumferences reflect overall body size, as well as body shape, and are correlated strongly positively with body mass index (BMI).MethodsWe evaluated body shape with the allometric body shape index (ABSI) and hip index (HI), which reflect waist and hip size among individuals with the same weight and height and are uncorrelated with BMI. We examined the associations of BMI, ABSI, and HI with platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) in multivariable linear regression models for 125,435 UK Biobank women and 114,760 men. We …

Background Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. Methods and findings We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for …

Background Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods We investigated associations of age at menarche and age at menopause, pregnancy‐related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results During 15 years of follow‐up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally …

BackgroundObesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related hormones and cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC) risk.MethodsNested case–control studies were conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (61 CGCs, and 172 NCGCs and matched controls) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study (100 CGCs and 65 NCGCs and matched controls); serum hormones were measured. In UK-Biobank (n = 458,713), we included 137 CGCs and 92 NCGCs. Sex-specific analyses were conducted. For EPIC and ATBC, odds ratios (ORs), and for UK-Biobank hazard ratios (HRs), were estimated using conditional logistic regression and Cox regression, respectively.ResultsInsulin-like …

Dietary biomarkers reflecting habitual diet are explored largely in European and American populations. However, the food metabolome is highly complex, with its composition varying to region and culture. Here, by assessing 1,055 plasma metabolites and 169 foods/beverages in 8,391 comprehensively phenotyped individuals from the multi-ethnic Asian HELIOS cohort (69% Chinese, 12% Malay, 19% South Asian), we report novel observations for ethnic-relevant and common foods. Using machine-learning feature selection approach, we developed dietary multi-biomarker panels (3-39 metabolites each) for key foods and beverages in respective training sets. These panels comprised distinct and shared metabolite networks, and captured variances in intake prediction models in test sets better than single biomarkers. Composite metabolite scores, derived from the biomarker panels, associated significantly and more strongly with clinical phenotypes (HOMA-IR, type 2 diabetes, BMI, fat mass index, carotid intima-media thickness and hypertension), compared to self-reported intakes. Lastly, in 235 individuals that returned for a repeat visit (averaged 322 days apart), diet-metabolite relationships were robust over time, with predicted intakes, derived from biomarker panels and metabolite scores, showing better reproducibility than self-reported intakes. Altogether, our findings show new insights into multi-ethnic diet-related metabolic variations and new opportunity to link exposure to health outcomes in Asian populations.

Aims/hypothesisEpidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.MethodsWe developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (p<5×10−8) SNPs permitted to be in weak linkage disequilibrium (r2<0.20). Summary …

Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes | Leukemia Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Leukemia View all journals Search My Account Explore content About the journal Publish with us Sign up for alerts RSS feed 1.nature 2.leukemia 3.corrections 4.article Download PDF Correction Published: 04 September 2023 Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes Sonja I. Berndt ORCID: orcid.org/0000-0001-5230-0652 1 na1 , Joseph Vijai 2 na1 , …

BackgroundDiet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).MethodsThis analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons.ResultsConsumption of n-6 γ-linolenic acid was …

BackgroundIron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.MethodsWe examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.ResultsOf 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse …

BackgroundGenomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.ObjectiveTo identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.Design, setting, and participantsData from 32 studies that includes 13,790 bladder cancer cases and 343, 502 controls of European ancestry were used for meta-analysis.Outcome measurements and statistical analysesLog-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking.Results and limitationsMultiple novel …

these results suggest that genetic and lifestyle related metabolic factors carry similar relative risk for dementia, as the prevalence of higher genetic risk is much lower than the prevalence of lifestyle related metabolic factors in the general population, the absolute number of cases of dementia attributable to the latter may be much higher. In view of the methodological pitfalls and complexities of evaluating individual dietary nutrients, extreme caution is warranted when interpreting results of such analyses. The AHA recommendation to adopt a “healthy dietary pattern” is in line with several observational studies that investigated the relationship between diet and dementia risk. In view of the available evidence from epidemiological studies and results of nonpharmacological multi-domain lifestyle RCTs (9), the focus of primary and secondary prevention for late onset dementias should remain in agreement with the public …

In June, 2023, a Working Group of 25 scientists from 12 countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to finalise their evaluation of the carcinogenicity of aspartame, methyleugenol, and isoeugenol. Aspartame was classified as “possibly carcinogenic to humans”(Group 2B) based on “limited” evidence for cancer in humans. There was also “limited” evidence for cancer in experimental animals and “limited” mechanistic evidence. Methyleugenol was classified as “probably carcinogenic to humans”(Group 2A) based on “sufficient” evidence for cancer in experimental animals and “strong” mechanistic evidence, including studies in humanised mice and supported by mechanistic studies in exposed humans. Isoeugenol was classified as “possibly carcinogenic to humans”(Group 2B) based on “sufficient” evidence for cancer in experimental animals. For both methyleugenol and …

Background Diabetes, cardiovascular disease, and related cardiometabolic disturbances are increasing rapidly in the Asia-Pacific region. We investigated the contribution of excess adiposity, a key determinant of diabetes and cardiovascular risk, to unfavourable cardiometabolic profiles amongst Asian ethnic subgroups. Methods The Health for Life in Singapore (HELIOS) Study is a population-based cohort comprising multi-ethnic Asian men and women living in Singapore, aged 30-84 years. We analyzed data from 9,067 participants who had assessment of body composition by Dual X-Ray Absorptiometry (DEXA) and metabolic characterization. We tested the relationship of BMI and visceral Fat Mass Index (vFMI) on cardiometabolic phenotypes (glycemic indices, lipid levels, and blood pressure), disease outcomes (diabetes, hypercholesterolemia, and hypertension), and metabolic syndrome score with multivariate regression analyses. Findings Participants were 59.6% female, with mean (SD) age 52.8 (11.8) years. The prevalence of diabetes, hypercholesterolemia, and hypertension was 8.3%, 29% and 18.0%, respectively. Malay and Indian participants had 3-4 folds higher odds of obesity and diabetes, and showed adverse metabolic and adiposity profiles, compared to Chinese participants. Excess adiposity contributed to all adverse cardiometabolic health indices including diabetes (P<0.001). However, while vFMI explained the differences in triglycerides and blood pressure between the Asian ethnic groups, increased vFMI did not explain higher glucose levels, reduced insulin sensitivity and risk of diabetes amongst Indian participants …

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence‐based survivorship recommendations. We performed a systematic review and meta‐analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow‐up observational analyses of patients enrolled in clinical trials. In linear dose‐response meta‐analysis of the observational studies, each 10‐unit increase in metabolic equivalent of task (MET)‐h/week higher recreational physical activity was associated with 15% and 14% lower risk of all‐cause (95% confidence interval [CI]: 8%‐22%, studies = 12, deaths = 3670) and breast cancer …

BackgroundSkin diseases impact significantly on the quality of life and psychology of patients. Obesity has been observed as a risk factor for skin diseases. Skin epidermal barrier dysfunctions are typical manifestations across several dermatological disturbances.ObjectivesWe aim to establish the association between obesity and skin physiology measurements and investigate whether obesity may play a possible causal role on skin barrier dysfunction.MethodsWe investigated the relationship of obesity with skin physiology measurements, namely transepidermal water loss (TEWL), skin surface moisture and skin pH in an Asian population cohort (n = 9990). To assess for a possible causal association between body mass index (BMI) and skin physiology measurements, we performed Mendelian Randomization (MR), along with subsequent additional analyses to assess the potential causal impact of known …

BackgroundObesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study.MethodsThe Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30–84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ‘g' was …

BackgroundAssociations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI).MethodsWe evaluated body shape with the allometric “a body shape index” (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.ResultsDuring a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 …

BackgroundPlatelet count (PLT) is associated positively with lung cancer risk but has a more complex association with body mass index (BMI), positive only in women (mainly never smokers) and inverse in men (mainly ever smokers), raising the question whether platelets interact with obesity in relation to lung cancer risk. Prospective associations of platelet size (an index of platelet maturity and activity) with lung cancer risk are unclear.MethodsWe examined the associations of PLT, mean platelet volume (MPV), and platelet distribution width (PDW) (each individually, per one standard deviation increase) with lung cancer risk in UK Biobank men and women using multivariable Cox proportional hazards models adjusted for BMI and covariates. We calculated Relative Excess Risk from Interaction (RERI) with obese (BMI ≥ 30 kg/m2), dichotomising platelet parameters at ≥ median (sex-specific), and multiplicative …

BackgroundHigher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk.ObjectivesTo explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies.MethodsConditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts.ResultsIn EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93 …

IntroductionLipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson’s disease (PD) in small-scale retrospective case–control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case–control study within a large European prospective cohort.MethodsA total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase …

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta‐analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random‐effects linear dose‐response meta‐analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta‐analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta‐analysis was only possible for all‐cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25‐hydroxyvitamin D (25(OH)D), and for …

PurposeThe incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype.MethodsWe analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21–2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake …

Background Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts. Methods We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline. Results Some associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most …

Simple Summary Malignant pleural mesothelioma (MPM) is an aggressive and still incurable cancer. There is an urgent need to identify effective and reliable tools for detecting and diagnosing the early onset of MPM. In our study, we investigated the whole miRNAs expression profile from serum extracellular vesicles to identify early changes related to MPM development. miR-11400, miR-148a-3p, and miR-409-3p levels were increased in pre-clinical MPM patients up to five years before their diagnosis. The three-miRNA pattern showed a good discrimination capacity to distinguish pre-clinical MPM from cancer-free controls. The three miRNAs also displayed high diagnostic capabilities for differentiating between MPM patients and controls. This study identified a potential EV miRNA signature in preclinical MPM up to five years before diagnosis and raises the possibility of early intervention. Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04 …

BackgroundAlcohol 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.ObjectiveLeveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk.MethodsWithin 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 …

Background End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 …

Background Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW …

Background and aimsThis study aimed to expand the European Prospective Investigation into Cancer and Nutrition (EPIC) nutrient database (ENDB) by adding amino acid (AA) values, using the U.S. nutrient database (USNDB). Additionally, we aimed to evaluate these new protein and AA intake estimates from the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR) using different matching procedures.Methods and resultsDietary energy, protein and AA intakes were assessed via DQ and 24-HDR by matching with the USNDB food composition table. Energy and protein intakes calculated using USNDB matching were compared with those calculated using ENDB, that uses country specific food composition tables. Pearson correlations, Cohen's weighted kappa statistic and Bland–Altman plots were used to compare data resulting from USNDB matching with our reference from ENDB matching.Very …

Associations of sex steroids and their binding proteins with body shape are unclear, because waist and hip circumference are correlated strongly with body size. We defined body shape using “a body shape index” (ABSI) and hip index (HI), which are independent of weight and height by design, and examined associations in multivariable generalised linear models for the UK Biobank cohort (179,902 men, 207,444 women). Total testosterone was associated inversely with ABSI, especially in men. Free testosterone was lowest for large-ABSI-large-HI (“wide”) and highest for small-ABSI-small-HI (“slim”) in men, but lowest for small-ABSI-large-HI (“pear”) and highest for large-ABSI-small-HI (“apple”) in women. Oestradiol was associated inversely with ABSI in obese pre-menopausal women but positively with HI in obese men and post-menopausal women not using hormone replacement therapy. Sex-hormone binding …

Background & AimsTo summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk.MethodsWe systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn’s disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding.ResultsThis study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric …

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations …

Background Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types. Results We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio …

Associations of liver, metabolic, and inflammatory biomarkers in blood with body shape are unclear, because waist circumference (WC) and hip circumference (HC) are dependent on overall body size, resulting in bias. We have used the allometric “a body shape index” (ABSI = WC(mm)Weight(kg)-2/3Height(m)5/6) and hip index (HIwomen = HC(cm)Weight(kg)-0.482Height(cm)0.310, HImen = HC(cm)Weight(kg)-2/5Height(cm)1/5), which are independent of body mass index (BMI) by design, in multivariable linear regression models for 121,879 UK Biobank men and 135,559 women. Glucose, glycated haemoglobin (HbA1c), triglycerides, low-density-lipoprotein cholesterol, apolipoprotein-B, alanine aminotransferase (ALT), gamma-glutamyltransferase, and lymphocytes were associated positively with BMI and ABSI but inversely with HI. High-density-lipoprotein cholesterol and …

Objective The purpose of this study was to quantify the effect of physical activity (in both descriptive and intervention studies) on health-related quality of life (HRQOL) in children and adolescents from both healthy and chronic illness populations. Method A systematic review of PubMed, PsycINFO, and ProQuest identified 33 studies of physical activity and HRQOL in youth, including descriptive and prepost intervention designs. Results In descriptive studies (N= 14), there was a small, positive association between physical activity and HRQOL based on child-reports (Hedges’g=. 302, p<. 001, 95% confidence interval, CI [. 178,. 426]) and a negligible association based on parent-proxy reports (Hedges’g=. 115, p=. 101, 95% CI [−. 023,. 253]). Intervention studies (N= 19) yielded a small, positive effect of physical activity intervention on HRQOL based on child-reports (Hedges’g=. 279, p=. 014, 95% CI [. 057,. 500]) and a …

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 …

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted …

Background:Open Access CommentComment on Muzzioli et al. Are Front-of-Pack Labels a Health Policy Tool? Nutrients 2022, 14, 771

BackgroundThere are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease.MethodWe measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore.ResultsThe Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American …

Background Nutrition is a well-established risk factor for cardiovascular diseases (CVD) that can be leveraged by public health prevention strategies. In addition to dietary guidelines, front-of-pack nutrition labels (FoPNL) can help consumers make healthier food choices. Nutri-Score, a scientifically validated 5-color FopNL based on the nutrient profile FSAm-NPS has been adopted by several European countries but remains optional under current EU labeling regulation, which is to be revised end of 2022. Scientific evidence is therefore needed on the relevance of the Nutri-Score at the European level. Our objective was to study the association between the consumption of food as graded by the FSAm-NPS and CVD risk in a large European population. Methods This prospective analysis was conducted on a case-cohort comprising 13,308 participants without CVD risk factors at …

Aims This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. Methods and results EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking …

Background and AimsIt is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn’s disease (CD) and ulcerative colitis (UC).MethodsWe conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs).ResultsAmong 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 …

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone‐binding globulin (SHBG) with aggressive, overall and early‐onset prostate cancer. In blood‐based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 …

It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow‐up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87‐0.96), fruit (HR = 0.91, 95% CI 0.86‐0.96) and vitamin C (HR = 0.91, 95% CI 0.86‐0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95 …

Previous studies have suggested that components of one‐carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case‐control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5′‐phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP …

Background Although a potential inverse association between vegetable intake and bladder cancer risk has been reported, epidemiological evidence is inconsistent. This research aimed to elucidate the association between vegetable intake and bladder cancer risk by conducting a pooled analysis of data from prospective cohort studies. Methods Vegetable intake in relation to bladder cancer risk was examined by pooling individual-level data from 13 cohort studies, comprising 3203 cases among a total of 555,685 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox proportional hazards regression models stratified by cohort for intakes of total vegetable, vegetable subtypes (i.e. non-starchy, starchy, green leafy and cruciferous vegetables) and individual vegetable types. In …

Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe. Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we …

Background Ethnic Asians are known to exhibit worse metabolic phenotypes as compared to Caucasians despite lower body mass index1, 2. Ethnic South-Asians and Malays were also found to display greater insulin resistance than Chinese3. One potential biological mechanism for this phenomenon is the inter-ethnic differences in the visceral adiposity deposition4. Here we hypothesised that visceral adiposity contributes to ethnic differences in metabolic phenotype more than subcutaneous adiposity. Methods We quantified total, subcutaneous and visceral adipose deposition (BMI, waist circumferences, Dual-energy X-ray absorptiometry [DEXA]) and metabolic phenotypes (blood pressure, fasting glucose and lipid profile, HbA1c) in 3403 participants. Analyses were adjusted for age, and sex. Results Participants were 40.6% male, mean age 49.7±11.4 years, Chinese: Malays: South-Asians in 72:9:19 ratio. Ethnic …

BackgroundHypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories.MethodsWe used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled …

Background Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in …

BackgroundVitamin 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.ObjectivesWe 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.MedthodsDietary 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 …

Background Several biological pathways implicated in cancer risk rely on vitamin B6, which can be measured in its active form pyridoxal 5’-phosphate (PLP). Functional markers of B6 enzymatic activity have been proposed, including the homocysteine:cysteine ratio (Hcy:Cys, a marker of transsulfuration), 3-hydroxykynurenine ratio (HKr, a marker of tryptophan catabolism), and the 4-pyridoxic acid ratio (PAr, a marker of B6 catabolism). We investigated the extent to which these markers are associated with B6 intake. Methods Data from 4,750 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study were included. We estimated the expected percentage change in each of the markers (PLP, Hcy:Cys, HKr, and PAr) for a doubling in B6 intake using log-linear Bayesian hierarchical regression models with log-transformed intake and biomarker data. Results The percent change …

Background Incidence of renal cell carcinoma (RCC) is two-fold higher in men compared with women. This ratio has been remarkably stable, both geographically and over time. We investigated whether established risk factors for RCC can explain the higher incidence in men. Methods 230,399 participants in the EPIC cohort study with complete data for BMI, history of hypertension, and smoking variables were included. Cox regression models with age as the time-scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for sex. Results We identified 690 incident RCC cases. The marginal HR [95% CI] for men versus women was 2.30 [1.98, 2.69]. There was no strong evidence for interactions between hypertension, BMI, or smoking status and sex. Adjusting for BMI, hypertension and smoking variables did not materially affect the estimate (HR: 2.18 [1.85, 2.56]), accounting for only 10% of the …

BackgroundUnhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates.MethodsUsing data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models …

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling …

Background Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991–2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. Results A …

Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case‐cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country‐specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice‐weighted Cox regression models and pooled results using random‐effects meta‐analysis. We found no evidence for …

The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01 …

Background An “obesity paradox” has been reported in kidney cancer, whereby obesity is a risk factor, yet appears to be associated with better survival. To evaluate this paradox, we investigated the association between pre-diagnostic adiposity and renal cell carcinoma (RCC) incidence and mortality. Methods Using data from 363,521 men and women in the European Prospective Investigation into Cancer and Nutrition (EPIC), Cox regression models yielded confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for RCC incidence and mortality in relation to BMI modelled continuously and using restricted cubic splines. RCC-specific and all-cause mortality were evaluated among cases. Results During a mean follow-up of 14.9 years, 936 incident RCC cases were identified, 383 of whom died (278 due to RCC). Each 5 kg/m2 increment in BMI was associated with 27% and 46% higher RCC …

Background Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population. Methods and findings We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10–P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total …

Background and aimsEmerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.MethodsDietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations …

BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse …

Background Body mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk. Methods We used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large …

Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow‐up of 7 years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR = 1.14; 95% confidence interval 1.03–1.26 per one standard deviation increment), esophagus (adenocarcinoma, HR = 1.27; 1.12–1.44), gastric cardia (HR = 1.31; 1.07–1.61), colon (HR = 1.18; 1.10–1.26), rectum (HR …

Background Colorectal cancer represents a major public health concern and there is a worrying tendency of increasing incidence rates among younger people in the last decades. Risk stratification of high-risk individuals may aid targeted disease prevention. We therefore aimed to evaluate the predictive value of a wide range of lifestyle and biomarker variables using data within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods A range of lifestyle, anthropometric and dietary variables in 329,885 participants in the EPIC cohort were evaluated as potential predictors for risk of colorectal cancer over 10 years. Biomarker measurements of 41 parameters were available for 1,320 CRC cases and 1,320 controls selected using incidence density matching. Best sets of predictors were selected using elastic net regularization with bootstrapping. Random survival forest was applied as a …

Background Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low-and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population. Methods and findings We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) updated food and: Pleaseverifythatallentriesarecorrect drink. Associations were: assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P 10–P 90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95 …

Background The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. Methods Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. Results In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable …

Evidence on the effects of meat consumption from different sources on the risk of bladder cancer (BC) is limited and controversial. Therefore, this study aimed to evaluate the associations between meat consumption and BC risk using a pooled data approach. Individual data from 11 prospective cohorts comprising 2848 BC cases and 515,697 non-cases with a total of 5,498,025 person-years of follow-up was pooled and analysed to investigate the potential associations between total red meat and products, red meat, processed meat, poultry and total fish and BC risk. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox regression models stratified on cohort. Overall, an increased BC risk was found for high intake of organ meat (HR comparing highest with lowest tertile: 1.18, 95% CI: 1.03, 1.36, p-trend = 0.03). On the contrary, a marginally inverse association was …

Background Alcohol consumption is causally linked to several cancer sites but the evidence for stomach cancer is still inconclusive. We aimed to quantify the association between alcohol intake and risk of stomach cancer, including subtypes. Methods We pooled data from two cohort studies including 452,958 individuals enrolled in the European Prospective Investigation into Cancer in 1992-98 and 38,756 Australians enrolled in the Melbourne Collaborative Cohort Study in 1990-94. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident stomach cancer were estimated using Cox regression. Results 1,225 incident stomach cancers were diagnosed over 7,094,637 person-years. Alcohol intake was not associated with overall stomach cancer risk. We observed a weak positive dose-response association for lifetime intake with non-cardia stomach cancer (HR = 1.03, 95% CI: 1.00-1.06/per 10 g …

Background Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). Methods and findings We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI …