| 1. |
- Rohrmann, Sabine, et al.
(författare)
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Meat consumption and mortality : results from the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 11, s. 63-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality.Results: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality.Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.
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| 2. |
- Aleksandrova, Krasimira, et al.
(författare)
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Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score
- 2021
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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| 3. |
- Castro-Espin, Carlota, et al.
(författare)
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Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries : results from the EPIC cohort study
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality.Methods: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0–5), medium (score 6–8), and high (score 9–16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality.Results: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01–1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84–1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87–0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72–0.91).Conclusions: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.
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| 4. |
- Freisling, Heinz, et al.
(författare)
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Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study
- 2020
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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| 5. |
- His, Mathilde, et al.
(författare)
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Lifestyle correlates of eight breast cancer-related metabolites : a cross-sectional study within the EPIC cohort
- 2021
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2).Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786).Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed.Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.
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| 6. |
- Matta, Michèle, et al.
(författare)
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Dietary intake of trans fatty acids and breast cancer risk in 9 European countries
- 2021
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01–1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03–1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01–1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.
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| 7. |
- Mayén, Ana-Lucia, et al.
(författare)
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Hepatic steatosis, metabolic dysfunction and risk of mortality : findings from a multinational prospective cohort study
- 2024
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality.METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed.RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality.CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.
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| 8. |
- Nimptsch, Katharina, et al.
(författare)
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Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach.Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry.Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37).Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
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| 9. |
- Rothwell, Joseph A., et al.
(författare)
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Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
- 2023
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.Methods: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.Results: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.Conclusions: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
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