Ecological studies showed correlations between a shift toward animal-protein-rich diets and longer life-expectancy; however, only a few studies examined individual-level association of protein source ...and mortality risks using appropriate iso-caloric substitution models adjusted for total energy intake. We used EPIC-Heidelberg (European Prospective Investigation into Cancer and nutrition) to create iso-caloric substitution models and determined relative all-cause, cardiovascular and cancer mortality hazards associated with dietary intake of animal protein and other macronutrients, employing Cox proportional hazard models. For comparison with other studies, we also synthesized evidence from a systematic review relating animal protein intake to mortality risk from seven prospective cohort studies in the USA, Europe and Japan. Substitution of 3% of total energy from animal protein for fat (saturated, mono-unsaturated) and carbohydrate (simple, complex) was associated with all-cause mortality (Hazard Ratios HR from 1.05 to 1.11), mostly driven by cardiovascular mortality (HR from 1.13 to 1.15). Independently of animal protein, substituting poly-unsaturated fat for saturated fat increased cancer-related mortality risk by 12 percent. The systematic review largely corroborated our findings. Overall, higher proportions of dietary energy from animal protein, combined with low energy intake from either carbohydrate sub-types or dietary fats, increases all-cause and cardiovascular mortality risks, but not cancer-related mortality.
Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been ...scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.
In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs.
During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles.
Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
While prior prospective iso-caloric substitution studies show a robust association between higher intake of animal protein and risk of mortality, associations observed for mortality risk in relation ...to major food sources of animal protein have been generally more diverse. We used the EPIC-Heidelberg cohort to examine if confounding, notably, by smoking, adiposity, or alcohol intake, could cause inconsistencies in estimated mortality hazard ratios (HR) related to intake levels of different types of meat and dairy products. Higher intakes of red or processed meats, and lower intakes of milk or cheese, were observed among current heavy smokers, participants with obesity, or heavy alcohol drinkers. Adjusting for age, sex, and total energy intake, risk models showed increased all-cause, cardiovascular, and cancer-related mortality with higher red or processed meat intakes (HR ranging from 1.25 95% confidence interval = 1.15-1.36 to 1.76 1.46-2.12 comparing highest to lowest tertiles), but reduced risks for poultry, milk, or cheese (HR ranging from 0.55 0.43-0.72 to 0.88 0.81-0.95). Adjusting further for smoking history, adiposity indices, alcohol consumption, and physical activity levels, the statistical significance of all these observed was erased, except for the association of processed meat intake with cardiovascular mortality (HR = 1.36 CI = 1.13-1.64) and cheese intake with cancer mortality (HR = 0.86 0.76-0.98), which, however, were substantially attenuated. These findings suggest heavy confounding and provide little support for the hypothesis that animal protein, as a nutrient, is a major determinant of mortality risk.
An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and ...lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).
Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.
Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk RR per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity P-het < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.
The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain ...natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HR
Q4-Q1
ranged from 1.781.36, 2.34 for breast cancer, when combining NT-proBNP and HbA1C, to 2.872.15, 3.83 for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.
Adult weight gain is positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk. To date, no meta-analysis has been conducted to assess ...this association by estrogen receptor (ER) and progesterone receptor (PR) status. We searched PubMed for relevant studies published through March 2010. Summarized risk estimates (REs) with 95% confidence intervals (CIs) were calculated using random effects or fixed effects models. We retrieved nine articles on weight gain from adulthood to reference age and ER- and/or PR-defined breast cancer risk, reporting on three prospective cohort studies and eight case-control studies. Comparing the highest versus the lowest categories of adult weight gain, risk was increased for ER⁺PR⁺ and ER⁺ tumors combined (11 studies; RE = 2.03; 95% CI 1.62, 2.45). Statistically significant heterogeneity (p heterogeneity = 0.002) was shown between REs for a mixed population of pre- and postmenopausal women combined (4 studies; RE = 1.54; 95% CI 0.86, 2.22) and for postmenopausal women only (7 studies; RE = 2.33; 95% CI 2.05, 2.60). Risk for ER⁻PR⁻ tumors among postmenopausal women was also slightly increased (7 studies; RE = 1.34; 95% CI 1.06, 1.63), but statistically significantly different from risk for ER⁺PR⁺ tumors (p heterogeneity < 0.0001). No associations were observed for ER⁺PR⁻ tumors whereas risk for ER⁻PR⁺ tumors could not be assessed. In conclusion, the association between adult weight gain and postmenopausal breast cancer risk is heterogeneous according to ER/PR status and stronger for ER⁺PR⁺ than for ER⁻PR⁻ tumors.
Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the ...amount and type of meat or fish consumed.
A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
In the dietary intervention study, 4 groups of 10 subjects consumed increasing quantities of chicken, red meat, processed meat, and fish over 3 successive weeks. Twenty-four-hour urine samples were collected during each period and analyzed by high-resolution liquid chromatography-mass spectrometry. Signals characteristic of meat or fish intake were replicated in 50 EPIC subjects for whom a 24-h urine sample and 24-h dietary recall were available and who were selected for their exclusive intake or no intake of any of the 4 same foods.
A total of 249 mass spectrometric features showed a positive dose-dependent response to meat or fish intake in the intervention study. Eighteen of these features best predicted intake of the 4 food groups in the EPIC urine samples on the basis of partial receiver operator curve analyses with permutation testing (areas under the curve ranging between 0.61 and 1.0). Of these signals, 8 metabolites were identified. Anserine was found to be specific for chicken intake, whereas trimethylamine-
oxide showed good specificity for fish. Carnosine and 3 acylcarnitines (acetylcarnitine, propionylcarnitine, and 2-methylbutyrylcarnitine) appeared to be more generic indicators of meat and meat and fish intake, respectively.
The meat and fish biomarkers identified in this work may be used to study associations between meat and fish intake and disease risk in epidemiologic studies. This trial was registered at clinicaltrials.gov as NCT01684917.
Inclusion of clinical parameters limits the application of most cardiovascular disease (CVD) prediction models to clinical settings. We developed and externally validated a non-clinical CVD risk ...score with a clinical extension and compared the performance to established CVD risk scores. We derived the scores predicting CVD (non-fatal and fatal myocardial infarction and stroke) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 25,992, cases = 683) using competing risk models and externally validated in EPIC-Heidelberg (n = 23,529, cases = 692). Performance was assessed by C-indices, calibration plots, and expected-to-observed ratios and compared to a non-clinical model, the Pooled Cohort Equation, Framingham CVD Risk Scores (FRS), PROCAM scores, and the Systematic Coronary Risk Evaluation (SCORE). Our non-clinical score included age, gender, waist circumference, smoking, hypertension, type 2 diabetes, CVD family history, and dietary parameters. C-indices consistently indicated good discrimination (EPIC-Potsdam 0.786, EPIC-Heidelberg 0.762) comparable to established clinical scores (thereof highest, FRS: EPIC-Potsdam 0.781, EPIC-Heidelberg 0.764). Additional clinical parameters slightly improved discrimination (EPIC-Potsdam 0.796, EPIC-Heidelberg 0.769). Calibration plots indicated very good calibration with minor overestimation in the highest decile of predicted risk. The developed non-clinical 10-year CVD risk score shows comparable discrimination to established clinical scores, allowing assessment of individual CVD risk in physician-independent settings.
The aim of the study was to examine the prospective association between life satisfaction and risk of type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. Previous studies suggested ...that psychosocial factors may affect the development of chronic diseases but the impact of positive attitudes, in particular life satisfaction, is yet to be determined.
The analysis included 50,358 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study in Potsdam and Heidelberg. Life satisfaction was assessed in a baseline interview and incident cases of chronic diseases were identified and verified during follow-up. Hazard ratios were calculated using Cox proportional hazards regression models that were systematically multivariable-adjusted for established risk factors and prevalent diseases.
During an average of 8 years of follow-up 2,293 cases of cancer, 1,840 cases of type 2 diabetes mellitus, 440 cases of stroke, and 562 cases of myocardial infarction were observed. Women who were unsatisfied with life at baseline showed in all models a significantly increased risk of cancer (HR: 1.45; 95% CI: 1.18-1.78) and stroke (HR: 1.69; 95% CI: 1.05-2.73) as well as an increased risk of type 2 diabetes mellitus by trend across categories (p-trend=0.04) compared to women very satisfied with life. In men, a relationship between life satisfaction and stroke was found but did not persist after consideration of lifestyle factors and prevalent diseases. No significant association was observed between life satisfaction and risk of myocardial infarction.
The results of this study suggest that reduced life satisfaction is related to the development of chronic diseases--particularly in women and partly mediated by established risk factors.
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