Showing papers by "Petra H.M. Peeters published in 2015"
Bjarni J. Vilhjálmsson1, Jian Yang2, Hilary K. Finucane3, Alexander Gusev4 +391 more•Institutions (14)
TL;DR: LDpred is introduced, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel, and outperforms the approach of pruning followed by thresholding, particularly at large sample sizes.
Abstract: Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.
1,088 citations
Norwegian School of Sport Sciences1, University of Cambridge2, Imperial College London3, Utrecht University4, Aalborg University5, Aarhus University6, University of Paris-Sud7, National and Kapodistrian University of Athens8, Academy of Athens9, Harvard University10, German Cancer Research Center11, International Agency for Research on Cancer12, University of Naples Federico II13, Lund University14, Umeå University15, University of Oxford16
TL;DR: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
260 citations
TL;DR: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength.
Abstract: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue.
160 citations
Joshua N. Sampson1, William Wheeler, Meredith Yeager1, Orestis A. Panagiotou1 +445 more•Institutions (113)
TL;DR: Correlation analysis indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the Genetic etiology for the same disease can vary by population and environmental exposures.
Abstract: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the add ...
158 citations
Emory University1, Charité2, Newcastle University3, Imperial College London4, University of Paris-Sud5, French Institute of Health and Medical Research6, German Cancer Research Center7, Academy of Athens8, National and Kapodistrian University of Athens9, University of Tromsø10, University of Granada11, Umeå University12, University of Oxford13, Prevention Institute14, Aarhus University15
TL;DR: The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.
Abstract: Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring seru ...
155 citations
Utrecht University1, University of Ulm2, University of Düsseldorf3, National and Kapodistrian University of Athens4, University College London5, Imperial College London6, University of Verona7, National Institute for Health and Welfare8, Norwegian Institute of Public Health9, University of Oslo10, Karolinska Institutet11, Aarhus University12, Aalborg University13, University of Oxford14, Swiss Tropical and Public Health Institute15, University of Basel16, University of Washington17, Université Paris-Saclay18, French Institute of Health and Medical Research19, University of Turin20, Netherlands Organisation for Applied Scientific Research21, Finnish Meteorological Institute22, University of Hertfordshire23
TL;DR: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality, and this association was robust to adjustment for other pollutants and PM 2.5 mass.
Abstract: Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality oBjectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter Methods: Mortality and confounder data from 19 European cohort studies were used Residential exposure to eight a priori–selected components of particulate matter (PM) was characterized following a strictly standardized protocol Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 25 μm (PM 25 ) and ≤ 10 μm (PM 10 ) were estimated using land-use regression models Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 143 years) Hazard ratios were positive for almost all elements and statistically significant for PM 25 sulfur (114; 95% CI: 106, 123 per 200 ng/m3) In a two-pollutant model, the association with PM 25 sulfur was robust to adjustment for PM 25 mass, whereas the association with PM 25 mass was reduced conclusions: Long-term exposure to PM 25 sulfur was associated with natural-cause mortality This association was robust to adjustment for other pollutants and PM 25 © 2015, Public Health Services, US Dept of Health and Human Services All rights reserved
130 citations
International Agency for Research on Cancer1, Massey University2, Aarhus University3, Cancer Council Victoria4, University of Melbourne5, Institut Gustave Roussy6, French Institute of Health and Medical Research7, South University8, Academy of Athens9, National and Kapodistrian University of Athens10, Harvard University11, University of Naples Federico II12, Utrecht University13, Imperial College London14, Andalusian School of Public Health15, University of Murcia16, Umeå University17, Lund University18, University of Oxford19
TL;DR: Having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women, suggesting programs which engage women in long term health behaviours should be supported.
Abstract: Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR=0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR=0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR=0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. What's new? How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention.
103 citations
TL;DR: The Dense Tissue and Early Breast Neoplasm Screening, or DENSE, trial is a multicenter RCT performed in the Dutch biennial population-based screening program and the primary outcome is the difference in the proportions of interval cancers between the study arms.
Abstract: Women with extremely dense breasts have an increased risk of breast cancer and lower mammographic tumor detectability. Nevertheless, in most countries, these women are currently screened with mammography only. Magnetic resonance (MR) imaging has the potential to improve breast cancer detection at an early stage because of its higher sensitivity. However, MR imaging is more expensive and is expected to be accompanied by an increase in the number of false-positive results and, possibly, an increase in overdiagnosis. To study the additional value of MR imaging, a randomized controlled trial (RCT) design is needed in which one group undergoes mammography and the other group undergoes mammography and MR imaging. With this design, it is possible to determine the proportion of interval cancers within each study arm. For this to be an effective screening strategy, the additional cancers detected at MR imaging screening must be accompanied by a subsequent reduction in interval cancers. The Dense Tissue and Early Breast Neoplasm Screening, or DENSE, trial is a multicenter RCT performed in the Dutch biennial population-based screening program (subject age range, 50-75 years). The study was approved by the Dutch Minister of Health, Welfare and Sport. In this study, mammographic density is measured by using a fully automated volumetric method. Participants with extremely dense breasts (American College of Radiology breast density category 4) and a negative result at mammography (Breast Imaging Recording and Data System category 1 or 2) are randomly assigned to undergo additional MR imaging (n = 7237) or to be treated according to current practice (n = 28 948). Participants provide written informed consent before the MR imaging examination, which consists of dynamic breast MR imaging with gadolinium-based contrast medium and is intended to be performed for three consecutive screening rounds. The primary outcome is the difference in the proportions of interval cancers between the study arms. Secondary outcomes are the number of MR imaging screening-detected cancers, proportions of false-positive results, diagnostic yield of MR imaging, tumor characteristics, quality of life, and cost effectiveness.
93 citations
University of Lyon1, International Agency for Research on Cancer2, Emory University3, Academy of Athens4, Institut Gustave Roussy5, French Institute of Health and Medical Research6, University of Paris-Sud7, Harvard University8, National and Kapodistrian University of Athens9, Prevention Institute10, University of Naples Federico II11, Imperial College London12, Utrecht University13, University of Granada14, Lund University15, University of Cambridge16, Cancer Epidemiology Unit17
TL;DR: Clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer are shown.
Abstract: Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer.
83 citations
Max Delbrück Center for Molecular Medicine1, Harvard University2, International Agency for Research on Cancer3, University of Oxford4, University of Ioannina5, National and Kapodistrian University of Athens6, Aarhus University7, Institut Gustave Roussy8, French Institute of Health and Medical Research9, University of Paris-Sud10, German Cancer Research Center11, Academy of Athens12, Imperial College London13, University of Naples Federico II14, Umeå University15, University of Cambridge16, Utrecht University17
TL;DR: The hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer is supported by the findings of this prospective nested case–control study.
Abstract: High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
77 citations
TL;DR: Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk, and weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones.
Abstract: Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise. Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5–6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry. Both the diet (−4.9 kg) and mainly exercise (−5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference −1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared. Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones. ClinicalTrials.gov identifier: NCT01511276
. Registered on 12 January 2012.
19 Feb 2015
TL;DR: Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
International Agency for Research on Cancer1, Institut Gustave Roussy2, French Institute of Health and Medical Research3, University of Melbourne4, Cancer Council Victoria5, Aarhus University6, Umeå University7, National and Kapodistrian University of Athens8, Academy of Athens9, Harvard University10, Imperial College London11, University of Naples Federico II12, Utrecht University13, University of Tromsø14, Andalusian School of Public Health15, University of Granada16, Lund University17, University of Cambridge18, University of Oxford19
TL;DR: In this article, the authors investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC), up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years.
Abstract: Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption.
International Agency for Research on Cancer1, South University2, French Institute of Health and Medical Research3, German Cancer Research Center4, Academy of Athens5, Harvard University6, University of Naples Federico II7, Utrecht University8, Imperial College London9, University of Tromsø10, Andalusian School of Public Health11, University of Murcia12, Lund University13, Umeå University14, University of Oxford15, University of Ioannina16, University of Cambridge17
TL;DR: The findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC.
Abstract: Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.
Imperial College London1, Carlos III Health Institute2, Utrecht University3, International Agency for Research on Cancer4, Emory University5, Institut Gustave Roussy6, French Institute of Health and Medical Research7, Aarhus University8, University of Granada9, University of Murcia10, University of Oxford11, Academy of Athens12, Harvard University13, National and Kapodistrian University of Athens14, Prevention Institute15, University of Naples Federico II16, Lund University17, Umeå University18, German Cancer Research Center19, University of Cambridge20
TL;DR: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0– 6i n men and 0–7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. (Continued on next page)
TL;DR: Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates than control groups offered an intervention after the intervention period.
Abstract: Purpose Important considerations for exercise trials in cancer patients are contamination and differential drop-out among the control group members that might jeopardize the internal validity. This systematic review provides an overview of different control groups design characteristics of exercise-oncology trials and explores the association with contamination and drop-out rates. Methods Randomized controlled exercise-oncology trials from two Cochrane reviews were included. Additionally, a computer-aided search using Medline (Pubmed), Embase and CINAHL was conducted after completion date of the Cochrane reviews. Eligible studies were classified according to three control group design characteristics: the exercise instruction given to controls before start of the study (exercise allowed or not); and the intervention the control group was offered during (any (e.g., education sessions or telephone contacts) or none) or after (any (e.g., cross-over or exercise instruction) or none) the intervention period. Contamination (yes or no) and excess drop-out rates (i.e., drop-out rate of the control group minus the dropout rate exercise group) were described according to the three design characteristics of the control group and according to the combinations of these three characteristics; so we additionally made subgroups based on combinations of type and timing of instructions received. Results 40 exercise-oncology trials were included based on pre-specified eligibility criteria. The lowest contamination (7.1% of studies) and low drop-out rates (excess drop-out rate -4.7+/-9.2) were found in control groups offered an intervention after the intervention period. When control groups were offered an intervention both during and after the intervention period, contamination (0%) and excess drop-out rates (-10.0+/-12.8%) were even lower. Conclusions Control groups receiving an intervention during and after the study intervention period have lower contamination and drop-out rates. The present findings can be considered when designing future exercise-oncology trials.
TL;DR: Non-smoking, a low BMI, being physically active, and adherence to a Mediterranean diet were associated with a lower disease burden and individuals adhering to all four healthy lifestyle characteristics lived a minimum of 2 years longer in good health than persons with none.
Abstract: The association between single health behaviours and incidence of and premature mortality from major chronic diseases, including myocardial infarction, stroke, diabetes mellitus, and cancer, has been demonstrated thoroughly. However, the association of several healthy behaviours with Disability-Adjusted Life Years (DALYs), which is a measure for total health combining Years Lost due to Disability and the Years of Life Lost due to premature mortality, has not been studied yet. A prospective cohort study was conducted among 33,066 healthy men and women aged 20 to 70 years recruited into the EPIC-NL study during 1993 to 1997. Participants’ smoking status, BMI, physical activity, and adherence to a Mediterranean-style diet (excluding alcohol) were investigated separately and combined into a simple health behaviour score ranging from 0 to 4. Participants were followed until the end of 2007 for occurrence of and mortality from the most important chronic diseases. The association between lifestyle (separate lifestyle factors and a simple health behaviour score) and DALYs were adjusted for relevant confounders. After a median follow-up of 12.4 years, 6,647 disease incidences and 1,482 deaths were documented. Non-smoking, low BMI (BMI <25), being physically active, and adherence to a Mediterranean diet were all associated with a significantly lower disease burden. Persons adhering to all four healthy lifestyle characteristics lived a minimum of 2 years longer in good health (DALYs: −2.13; 95% CI: −2.65 to −1.62) than persons with none. Due to our non-extinct cohort, the total number of DALYs, and consequently the estimates, is underestimated. Therefore, true lifetime health benefits of a healthy lifestyle will be even larger. Non-smoking, a low BMI, being physically active, and adherence to a Mediterranean diet were associated with a lower disease burden. Each additional healthy lifestyle factor contributed to a longer life in good health.
University of Turin1, University of Naples Federico II2, Aarhus University3, German Cancer Research Center4, University of Paris-Sud5, Institut Gustave Roussy6, National and Kapodistrian University of Athens7, Utrecht University8, Umeå University9, Lund University10, University of Tromsø11, University of Cambridge12, University of Oxford13, International Agency for Research on Cancer14, Imperial College London15
TL;DR: For example, the authors found that women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications.
Abstract: Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. What's new? For the first time, researchers have used cohort data to show that people who survive breast cancer have a higher risk of developing another cancer later. By collecting data on 10,000 breast cancer patients over 11 years, these authors calculated a 30% boost in the patients' risk of developing a second primary malignancy, particularly colorectal cancer, lymphoma, melanoma, endometrial cancer, and kidney cancer. These findings, plus the data they collected on risk factors such as age, smoking, body mass index, and others, will help guide clinicians in screening procedures and follow up care for breast cancer patients.
German Cancer Research Center1, Heidelberg University2, Queen's University Belfast3, National Institutes of Health4, Karolinska Institutet5, University of Tromsø6, Imperial College London7, Wageningen University and Research Centre8, National and Kapodistrian University of Athens9, Glostrup Hospital10, University of Copenhagen11, Lithuanian University of Health Sciences12, Umeå University13, University of Granada14, University of Insubria15, Icahn School of Medicine at Mount Sinai16
TL;DR: In this article, the authors report that smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited.
National and Kapodistrian University of Athens1, Harvard University2, Academy of Athens3, International Agency for Research on Cancer4, Emory University5, Max Delbrück Center for Molecular Medicine6, University of Ioannina7, Aarhus University8, French Institute of Health and Medical Research9, German Cancer Research Center10, Prevention Institute11, Imperial College London12, Utrecht University13, University of Tromsø14, University of Granada15, Umeå University16, Lund University17, Cancer Epidemiology Unit18, University of Cambridge19
TL;DR: The data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
National Institutes of Health1, International Agency for Research on Cancer2, German Cancer Research Center3, Imperial College London4, Umeå University5, University of Naples Federico II6, French Institute of Health and Medical Research7, University of Paris-Sud8, Institut Gustave Roussy9, National and Kapodistrian University of Athens10, Academy of Athens11, Harvard University12, University Medical Center13, University of Granada14, University of Murcia15, University of Cambridge16, University of Oxford17
TL;DR: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers.
Abstract: Purpose Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non‐type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis.
Ministry of Health (Malaysia)1, University of Malaya2, Utrecht University3, Imperial College London4, Aarhus University5, Institut Gustave Roussy6, University of Paris-Sud7, German Cancer Research Center8, National and Kapodistrian University of Athens9, University of Naples Federico II10, Prevention Institute11, Wageningen University and Research Centre12, University of Tromsø13, University of Granada14, Lund University15, Umeå University16, University of Cambridge17, Medical Research Council18, Cancer Epidemiology Unit19, International Agency for Research on Cancer20, Queen Mary University of London21
TL;DR: Higher caffeinated coffee consumption may be associated with lower risk of postmenopausal breast cancer, and decaffeinated coffee intake does not seem to be associatedWith breast cancer.
Abstract: Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR = 0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; P-trend = 0.029. While there was no significant effect modification by hormone receptor status (P = 0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P = 0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR = 0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (P-trend = 0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR = 0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.
German Cancer Research Center1, Aarhus University2, French Institute of Health and Medical Research3, University of Melbourne4, Academy of Athens5, National and Kapodistrian University of Athens6, Harvard University7, Prevention Institute8, Utrecht University9, University of Tromsø10, Andalusian School of Public Health11, Lund University12, Umeå University13, Cancer Epidemiology Unit14, University of Cambridge15, International Agency for Research on Cancer16, Imperial College London17
TL;DR: The data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity, and add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.
Abstract: Background: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating in ...
German Cancer Research Center1, Imperial College London2, Aarhus University3, Institut Gustave Roussy4, French Institute of Health and Medical Research5, University of Paris-Sud6, Cancer Council Victoria7, University of Melbourne8, Academy of Athens9, National and Kapodistrian University of Athens10, Harvard University11, University of Naples Federico II12, University of Turin13, Utrecht University14, University of Tromsø15, University of Granada16, Lund University17, Umeå University18, University of Cambridge19, University of Oxford20, International Agency for Research on Cancer21
TL;DR: Ass associations between reproductive and hormone‐related risk factors for EOC by subtype in theEPIC cohort are examined and limited heterogeneity is observed, suggesting limited heterogeneity between sexual orientation and EOC subtypes.
Abstract: Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (ie, dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review We observed significant heterogeneity by the dualistic model (ie, type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs type II [high grade serous or endometrioid]) for full-term pregnancy (p(het)=002) Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs never: type I: relative risk (RR) 047 [95% confidence interval (CI): 033-069]; type II, RR: 081 [061-106]) We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell) None of the investigated factors were associated with borderline tumors Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (eg, ever full-term pregnancy: serous, RR: 073 [058-092]; mucinous, RR: 053 [030-095]; endometrioid, RR: 065 [040-106]; clear cell, RR: 034 [018-064]; p(het)=016) These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes What's new? Reproductive and hormone-related risk factors for epithelial ovarian cancer (EOC) have been extensively investigated However, EOC is increasingly recognized as a heterogeneous disease and risk factor differences across EOC subtypes, as defined by the recently proposed dualistic pathway of ovarian carcinogenesis and histological characteristics, are not well understood Here, the authors present a detailed prospective investigation on reproductive and hormone-related risk factors for borderline tumors and epithelial ovarian cancer by main histological subtypes and, for the first time, by the types defined by the dualistic pathway The results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes
Utrecht University1, University Medical Center Utrecht2, Aarhus University3, Aalborg University4, French Institute of Health and Medical Research5, Institut Gustave Roussy6, University of Paris-Sud7, German Cancer Research Center8, Academy of Athens9, National and Kapodistrian University of Athens10, Harvard University11, Prevention Institute12, University of Turin13, University of Tromsø14, University of Granada15, University of Murcia16, Lund University17, Umeå University18, University of Cambridge19, Cancer Epidemiology Unit20, International Agency for Research on Cancer21, Imperial College London22
TL;DR: This study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow‐up of more than 10 years, but a lower risk of colon cancer is suggested with high consumption of fruit and vegetables.
Abstract: Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.
Imperial College London1, Harvard University2, Brigham and Women's Hospital3, University of Massachusetts Amherst4, University of Ioannina5, Cancer Epidemiology Unit6, Aarhus University7, French Institute of Health and Medical Research8, German Cancer Research Center9, Academy of Athens10, National and Kapodistrian University of Athens11, University of Turin12, University of Naples Federico II13, Utrecht University14, University of Tromsø15, University of Granada16, University of Murcia17, Lund University18, Umeå University19, University of Cambridge20, University of Oxford21, International Agency for Research on Cancer22
TL;DR: It is suggested that coffee intake may be inversely associated with endometrial cancer risk, and further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrian cancer risk to develop improved prevention strategies.
Abstract: Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR ≤ 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies.
Imperial College London1, Aarhus University2, French Institute of Health and Medical Research3, University of Paris-Sud4, Institut Gustave Roussy5, German Cancer Research Center6, Academy of Athens7, National and Kapodistrian University of Athens8, Harvard University9, Prevention Institute10, University of Turin11, University of Naples Federico II12, Utrecht University13, University of Tromsø14, University of Granada15, Lund University16, Umeå University17, University of Cambridge18, University of Oxford19, International Agency for Research on Cancer20
TL;DR: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes, and these findings may contribute to the development of improved strategies to promote better long-term health in women.
Abstract: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk. The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25–70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration. During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76–0.84), in women who had ever versus never breastfed (0.92; 0.87–0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86–0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85–0.96; P for trend = 0.038). Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
German Cancer Research Center1, International Agency for Research on Cancer2, Aarhus University3, French Institute of Health and Medical Research4, Cancer Council Victoria5, University of Melbourne6, Academy of Athens7, National and Kapodistrian University of Athens8, Harvard University9, University of Naples Federico II10, Utrecht University11, Imperial College London12, Lund University13, Umeå University14, University of Cambridge15, University of Oxford16
TL;DR: The findings support a possible role of androgens in ovarian carcinogenesis and additional studies exploring this association are needed.
Abstract: The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.
International Agency for Research on Cancer1, Emory University2, Academy of Athens3, National and Kapodistrian University of Athens4, Harvard University5, Aarhus University6, French Institute of Health and Medical Research7, Institut Gustave Roussy8, German Cancer Research Center9, University of Naples Federico II10, University of Turin11, Utrecht University12, Imperial College London13, University of Oslo14, Umeå University15, Lund University16, University of Cambridge17, University of Oxford18, Medical Research Council19
TL;DR: In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk, and restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings.
Abstract: The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.
University of Tromsø1, Heidelberg University2, German Cancer Research Center3, Imperial College London4, Utrecht University5, National and Kapodistrian University of Athens6, Cancer Epidemiology Unit7, Aarhus University8, Lund University9, University of Naples Federico II10, University Medical Center11, Umeå University12, University of Granada13, Prevention Institute14, International Agency for Research on Cancer15
TL;DR: The rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries is examined.
Abstract: Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992–1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).