Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk.

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E-4), and Aspartylglucosaminidase (AGA: p = 4.5E-4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.

Tea consumption and the risk of abdominal aortic aneurysm.

BACKGROUND: Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. METHODS: The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swedish Mammography Cohort (SMC), aged 45-83 years at baseline. The COSM was established in 1997 with all men who lived in two central Swedish counties (Västmanland and Örebro), and the SMC was established in 1987-1990 with women residing in Västmanland county. Tea consumption was assessed by means of food frequency questionnaires in 1997 and 2009. RESULTS: During 17.5 years of follow-up, 1781 AAA cases (1496 men, 285 women; 1497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. Tea consumption was inversely associated with total AAA incidence in men and women. Women had a 23 (95 per cent c.i. 8 to 36) per cent lower risk of AAA per each cup per day increment, whereas men had a 9 (0 to 17) per cent lower risk (Pinteraction = 0.029). Tea consumption was associated with a lower risk of both non-ruptured (hazard ratio (HR) 0.93, 95 per cent c.i. 0.85 to 1.01) and ruptured (HR 0.84, 0.71 to 0.98) AAA. Smoking status modified the association (Pinteraction < 0.001), whereby tea consumption was associated with lower risk of AAA in ex-smokers (per cup per day, HR 0.89, 0.80 to 0.98) and in never smokers (HR 0.88, 0.77 to 1.00), but not in current smokers (HR 0.95, 0.84 to 1.06). Tea consumption was associated with a lower risk in participants with (HR 0.88, 0.80 to 0.98) and without (HR 0.93, 0.88 to 1.00) hypertension, and in those with (HR 0.82, 0.67 to 1.01) and without (HR 0.92, 0.86 to 0.98) hypercholesterolaemia. CONCLUSION: Tea consumption was associated with a reduced risk of AAA. The association was more pronounced for ruptured than non-ruptured AAA, and in patients with hypertension and hypercholesterolaemia than those without. The association was also observed in ex-smokers and never smokers, but not in current smokers.

Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study.

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10-8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09-1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04-1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03-1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10-1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00-1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.

Adherence to the WCRF/AICR 2018 recommendations for cancer prevention and risk of cancer: prospective cohort studies of men and women.

BACKGROUND: In 2018, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) issued revised recommendations for cancer prevention. We examined the relation between adherence to these recommendations and risk of total cancer in two population-based Swedish prospective cohorts (29,451 men and 25,349 women). METHODS: Standardized-WCRF/AICR 2018 and simplified-WCRF/AICR 2018 adherence scores were constructed based on the WCRF/AICR recommendations for body weight, physical activity, diet, alcohol consumption and dietary supplement use. Data were collected using a self-administered questionnaire. RESULTS: During the 15.4 years of follow-up, 12,693 incident cancers were ascertained. The multivariable HR between extreme categories of the Standardized-WCRF/AICR 2018 score (4.1-7 vs. 0-2) was 0.88 (95% CI = 0.82-0.95) and for the Simplified score (5-8 vs. 0-2) was 0.85 (95% CI = 0.80-0.90); each 1-score increment in recommendation adherence was associated with 3% (95% CI = 1-5%) and 4% (95% CI = 2-5%) decreased risk, respectively. Based on the Simplified scoring, most participants (>90%) did not meet WCRF/AICR 2018 recommendations regarding consumption of plant foods, limited consumption of red/processed meat and 'fast food'/processed food, and <50% of participants met the weight and physical activity recommendations. CONCLUSIONS: Adherence to the 2018WCRF/AICR recommendations substantially reduced the risk of total cancer. Given that many people do not meet the recommendations, there is a great potential for cancer prevention.

Contrasting prenatal nutrition and environmental exposures in association with birth weight and cognitive function in children at 7 years.

BACKGROUND: Good nutrition is essential for individual health, a notion that is particularly true during pregnancy. We have used a nutrition index that measures the adequacy of one's diet relative to the unique nutritional needs of individuals due to, for example, their activity level, dietary restrictions, lifestyle and body size. The use of this personalised metric of dietary nutritiousness in the analysis of prenatal environmental exposures and developmental outcomes permits testing for potential mitigating effects of good nutrition. We also provide an analysis strategy for investigating the balance in beneficial food sources which are also the source of environmental toxicants. METHODS: A holistic measure of nutrition, My Nutrition Index (MNI), measures the nutrient quality (ie, 'nutritiousness') of a specified daily diet. MNI is calculated based on quantification of dozens of macronutrients and micronutrients that are specific to an individual's nutritional needs by incorporating dietary restrictions, subject characteristics, activity level and health behaviours. The Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy Study is a Swedish pregnancy cohort, with prenatal endocrine disrupting chemicals (EDCs) exposure and dietary data available. This makes it possible to test for the potential mitigating effects of good nutrition on health and development effects in offspring from EDCs. RESULTS: Using prenatal Food Frequency Questionnaire data to construct an individual's MNI, the index was significantly and positively associated with important metabolic outcome (as measured by birth weight) and cognitive function at age 7 years (as measured by WISC IQ) in children when adjusted for covariates and prenatal concentrations of an EDC. In a stratified analysis of 'low' and 'high' fish consumption, a potential source of perfluoro-octanesulfonic acid (PFOS), the association between PFOS and birth weight was diminished in the high consumption group compared with the low consumption group. CONCLUSIONS: Thus, MNI is evidently a metric of the general nutritiousness of daily diets and is useful in environmental health studies in representing the impact of good nutrition, even during pregnancy.

Dietary Intake of Polyunsaturated Fatty Acids and Pain in Spite of Inflammatory Control Among Methotrexate-Treated Early Rheumatoid Arthritis Patients.

OBJECTIVE: To investigate potential associations between dietary intake of polyunsaturated fatty acids (FAs) and pain patterns in early rheumatoid arthritis (RA) patients after 3 months of methotrexate (MTX) treatment. METHODS: We included 591 early RA patients with MTX monotherapy from a population-based prospective case-control study, the Epidemiological Investigation of Rheumatoid Arthritis. Dietary data on polyunsaturated FAs (food frequency questionnaires) were linked with data on unacceptable pain (visual analog scale [VAS] >40 mm), noninflammatory/refractory pain (VAS >40 mm and C-reactive protein [CRP] level <10 mg/liter), and inflammatory pain (VAS >40 mm and CRP level >10 mg/liter) after 3 months. Statistical analysis included logistic regression. RESULTS: After 3 months of MTX treatment, 125 patients (21.2%) had unacceptable pain, of which 92 patients had refractory pain, and 33 patients had inflammatory pain. Omega-3 FA intake was inversely associated with unacceptable pain and refractory pain (odds ratio [OR] 0.57 [95% confidence interval (95% CI) 0.35-0.95] and OR 0.47 [95% CI 0.26-0.84], respectively). The omega-6:omega-3 FA ratio, but not omega-6 FA alone, was directly associated with unacceptable pain and refractory pain (OR 1.70 [95% CI 1.03-2.82] and OR 2.33 [95% CI 1.28-4.24], respectively). Furthermore, polyunsaturated FAs were not associated with either inflammatory pain or CRP level and erythrocyte sedimentation rate at followup. Omega-3 FA supplementation was not associated with any pain patterns. CONCLUSION: Omega-3 FA was inversely associated with, and the omega-6:omega-3 FA ratio was directly associated with, unacceptable and refractory pain, but not with inflammatory pain or systemic inflammation. The inverse association between omega-3 FA and refractory pain may have a role in pain suppression in RA.

High-dose B-vitamin supplements and risk for age-related cataract: a population-based prospective study of men and women.

Previous studies that have investigated the association between B-vitamin supplement use and risk for cataract yield conflicting results. The aim of this study was to examine the association between use of high-dose B-vitamin supplements (approximately 10 times recommended daily intake) and risk for age-related cataract in a population-based prospective study of 13 757 women from the Swedish Mammography Cohort and 22 823 men from the Cohort of Swedish Men. Dietary supplement use and potential confounders were assessed using a questionnaire at baseline. Information on cataract diagnosis and extraction was obtained through linkage to registers. During the follow-up period between January 1998 and December 2011, we identified 8395 cataract cases (3851 for women and 4544 for men). The use of B vitamins plus other supplements and B vitamins only was associated with 9 % (95 % CI 2, 17) and 27 % (95 % CI 12, 43) increased risk for cataract, respectively. The hazard ratios for use of B vitamins only and risk for cataract stratified by different age groups were as follows: <60 years: 1·88 (95 % CI 1·47, 2·39); 60-69 years: 1·21 (95 % CI 0·96, 1·53); and ≥70 years: 1·09 (95 % CI 0·91, 1·31) (P interaction=0·002). Our results suggest that the use of high-dose B-vitamin supplements was associated with an increased risk for cataract. This association might be confined to younger participants.

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study.

BACKGROUND: Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). METHODS: This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders. RESULTS: The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline. CONCLUSIONS: Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs.

Coffee Consumption and Risk of Gallbladder Cancer in a Prospective Study.

Evidence indicates that coffee consumption may reduce the risk of gallstone disease, which is strongly associated with increased risk of gallbladder cancer. The association between coffee consumption and gallbladder cancer incidence was examined in a prospective cohort study of 72 680 Swedish adults (aged 45 - 83 years) who were free of cancer and reported their coffee consumption at baseline. Gallbladder cancers were ascertained by linkage with the Swedish Cancer Register. The data were analyzed using Cox proportional hazards regression models. Statistical tests were two-sided. During 967 377 person-years of follow-up, 74 gallbladder cancer case patients were identified. Compared with consumption of one or less cups of coffee per day, the multivariable hazard ratios were 0.76 (95% confidence interval [CI] = 0.41 to 1.41) for two cups per day, 0.50 (95% CI = 0.24 to 1.06) for three cups per day, and 0.41 (95% CI = 0.20 to 0.83) for four or more cups per day. In conclusion, coffee consumption is associated with a reduced risk of gallbladder cancer.

Fish, long-chain omega-3 polyunsaturated fatty acid intake and incidence of atrial fibrillation: A pooled analysis of two prospective studies.

BACKGROUND & AIMS: Whether high intakes of fish and long-chain omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF) remains uncertain. Thus, we aimed to evaluate the associations of total fish, types of fish, and omega-3 PUFA intake with AF incidence in a large prospective study. METHODS: We used data from the Cohort of Swedish Men and the Swedish Mammography Cohort to examine the associations of fish consumption and long-chain omega-3 PUFA intake with AF incidence. At baseline, information on fish and omega-3 PUFA intakes was available from 72,984 men and women, aged 45-83 years, without cardiac disease. Cases of AF were identified through linkage with the Swedish National Patient Register. Multivariable-adjusted relative risks were estimated with the use of Cox proportional hazards models. RESULTS: Over a follow-up period of 12 years, 6095 participants (3595 men and 2500 women) developed AF. Intakes of total fish, fatty fish (herring/mackerel and salmon/whitefish/char), and long-chain omega-3 PUFAs were not associated with AF incidence after adjustment for other risk factors. However, high consumption of lean fish (cod/saithe/fish fingers) was associated with a lower risk; multivariable relative risk of AF for ≥3 servings/week compared with never consumption was 0.79 (95% confidence interval, 0.65-0.95). CONCLUSIONS: These findings do not support a beneficial association of fatty fish or omega-3 PUFA intake with incident AF. The association between lean fish consumption and AF risk warrants further investigation.

Potato consumption and risk of cardiovascular disease: 2 prospective cohort studies.

BACKGROUND: Whether consumption of potatoes, which are rich in potassium and have a high glycemic index and glycemic load, is associated with the risk of cardiovascular disease (CVD) is unknown. OBJECTIVE: The aim was to examine the association between potato consumption and risk of total and specific CVD events as well as mortality from CVD in 2 prospective cohorts of Swedish adults, a population with a high consumption of potatoes. DESIGN: Information on potato consumption was available from 69,313 men and women, free of CVD and diabetes, in the Cohort of Swedish Men and the Swedish Mammography Cohort. Nonfatal and fatal cases of CVD diagnosed over 13 y of follow-up were identified by linkage with the Swedish National Patient and Cause of Death Registers. Analyses were conducted by using a Cox proportional hazards regression model, controlled for potential confounders. RESULTS: We ascertained 10,147 major CVD events [myocardial infarction (MI), heart failure (HF), and stroke] and 4003 deaths due to CVD. Total potato consumption was not associated with the risk of major CVD events, specific CVD endpoints, or CVD mortality in either men or women. Multivariable HRs (95% CIs) per an increment of 3 servings/wk of total potato consumption (boiled potatoes, fried potatoes, and French fries) were 1.00 (0.97, 1.02) for major CVD events, 1.01 (0.97, 1.04) for MI, 0.97 (0.93, 1.02) for HF, 1.01 (0.97, 1.05) for stroke, and 0.99 (0.95, 1.03) for CVD mortality. There were no significant trends between the consumption of boiled potatoes, fried potatoes, or French fries and risk of any CVD outcome. CONCLUSION: Potato consumption was not associated with the risk of CVD in this population. The Swedish Mammography Cohort and the Cohort of Swedish Men are registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.

Associations of dietary polychlorinated biphenyls and long-chain omega-3 fatty acids with stroke risk.

BACKGROUND: Little is known about joint exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fatty acids [eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)], through fish consumption, on cerebrovascular disease risk. OBJECTIVE: To explore associations of dietary PCB exposure and EPA-DHA intake with risk of different stroke subtypes. METHODS: This was assessed in the prospective population-based Cohort of Swedish Men including 39,948, middle-aged and elderly men, who were free of cardiovascular disease and cancer at baseline in 1997. Validated estimates of dietary PCBs and EPA-DHA were obtained via a food frequency questionnaire. RESULTS: During 12years of follow-up, 2286 and 474 incident cases of ischemic stroke and hemorrhagic stroke, respectively, were ascertained through register linkage. Dietary PCB exposure and EPA-DHA intake were associated with hemorrhagic stroke but not ischemic stroke. Men in the highest quartile of dietary PCB exposure (median 412ng/day) had a multivariable- and EPA-DHA-adjusted RR of hemorrhagic stroke of 2.77 [95% confidence interval (CI), 1.48-5.19] compared with men in the lowest quartile (median 128ng/day; p for trend <0.01). The corresponding RRs in men with and without hypertension were 5.45 (95% CI, 1.34-22.1) and 2.37 (95% CI 1.17-4.79), respectively. The multivariable- and PCB-adjusted RR of hemorrhagic stroke for the highest quartile of EPA-DHA intake (median 0.73g/day) versus the lowest quartile (median 0.18g/day) was 0.42 (95% CI, 0.22-0.79). CONCLUSION: Dietary PCB exposure was associated with an increased risk of hemorrhagic stroke, whereas a protective association was observed for dietary EPA-DHA intake.

Ageing with elegans: a research proposal to map healthspan pathways.

Human longevity continues to increase world-wide, often accompanied by decreasing birth rates. As a larger fraction of the population thus gets older, the number of people suffering from disease or disability increases dramatically, presenting a major societal challenge. Healthy ageing has therefore been selected by EU policy makers as an important priority ( http://www.healthyageing.eu/european-policies-and-initiatives ); it benefits not only the elderly but also their direct environment and broader society, as well as the economy. The theme of healthy ageing figures prominently in the Horizon 2020 programme ( https://ec.europa.eu/programmes/horizon2020/en/h2020-section/health-demographic-change-and-wellbeing ), which has launched several research and innovation actions (RIA), like "Understanding health, ageing and disease: determinants, risk factors and pathways" in the work programme on "Personalising healthcare" ( https://ec.europa.eu/research/participants/portal/desktop/en/opportunities/h2020/topics/693-phc-01-2014.html ). Here we present our research proposal entitled "ageing with elegans" (AwE) ( http://www.h2020awe.eu/ ), funded by this RIA, which aims for better understanding of the factors causing health and disease in ageing, and to develop evidence-based prevention, diagnostic, therapeutic and other strategies. The aim of this article, authored by the principal investigators of the 17 collaborating teams, is to describe briefly the rationale, aims, strategies and work packages of AwE for the purposes of sharing our ideas and plans with the biogerontological community in order to invite scientific feedback, suggestions, and criticism.

A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis.

Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations and breast cancer risk.

The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case-control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI = 0.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR = 0.86; 95% CI = 0.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence.

Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies.

BACKGROUND: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. RESULTS: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. CONCLUSIONS: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.

Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men - A population-based prospective cohort study.

BACKGROUND: Major food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored. METHODS AND RESULTS: We assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113ng/day), men in the highest quintile (median 436ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30-2.33; p-trend<0.001) for total and 1.97 (95% CI 1.42-2.75; p-trend<0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction =0.03). CONCLUSIONS: Exposure to PCBs via diet was associated with increased risk of myocardial infarction in men.

Coffee consumption is not associated with increased risk of atrial fibrillation: results from two prospective cohorts and a meta-analysis.

BACKGROUND: Whether coffee consumption affects the risk of developing atrial fibrillation (AF) remains unclear. We sought to investigate the association between coffee consumption and incidence of AF in two prospective cohorts, and to summarize available evidence using a meta-analysis. METHODS: Our study population comprised 41,881 men in the Cohort of Swedish Men and 34,594 women in the Swedish Mammography Cohort who had provided information on coffee consumption in 1997 and were followed up for 12 years. Incident cases of AF were ascertained by linkage with the Swedish Hospital Discharge Register. For the meta-analysis, prospective studies were identified by searching PubMed and Embase through 22 July 2015, and by reviewing the reference lists of retrieved articles. Study-specific relative risks were combined using a random effects model. RESULTS: We ascertained 4,311 and 2,730 incident AF cases in men and women, respectively, in the two cohorts. Coffee consumption was not associated with AF incidence in these cohort studies. The lack of association was confirmed in a meta-analysis, including six cohort studies with a total of 10,406 cases of AF diagnosed among 248,910 individuals. The overall relative risk (95% confidence interval) of AF was 0.96 (0.84-1.08) for the highest versus lowest category of coffee consumption, and 0.99 (0.94-1.03) per 2 cups/day increment of coffee consumption. CONCLUSIONS: We found no evidence that coffee consumption is associated with increased risk of AF.