Imperial College London

DrDagfinnAune

Faculty of MedicineSchool of Public Health

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 8478d.aune

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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203 results found

Hibino M, Otaki Y, Kobeissi E, Pan H, Hibino H, Taddese H, Majeed Z, Verma S, Konta T, Yamagata K, Fujimoto S, Tsuruya K, Narita I, Kasahara M, Shibagaki Y, Iseki K, Moriyama T, Kondo M, Asahi K, Watanabe T, Watanabe T, Watanabe M, Aune Det al., 2021, Blood pressure, hypertension and the risk of aortic dissection incidence and mortality: results from the Japan-specific health checkups study, the UK biobank study and a metaanalysis of cohort studies, Circulation, ISSN: 0009-7322

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies.Methods: We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined.Results: In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >7

Journal article

Laine J, Huybrechts I, Gunter M, Ferrari P, Weiderpass E, Tsilidis K, Dagfinn A, Schulze M, Bergmann M, Temme E, Boer JMA, Agnoli C, Ericson U, Stubbendorff A, Ibsen DB, Dahm CC, Deschasaux M, Touvier M, Kesse-Guyot E, Sánchez M-J, Barranco MR, Tong TYN, Papier K, Knuppel A, Boutron-Ruault M-C, Mancini F, Severi G, Srour B, Kühn T, Masala G, Agudo A, Skeie G, Rylander C, Sandanger TM, Riboli E, Vineis Pet al., 2021, Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study, The Lancet Planetary Health, Vol: 5, Pages: e786-e796, ISSN: 2542-5196

Background: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas (GHG) emissions, substantial land use, (LU) and adverse health outcomes such as cancer and mortality. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study (n=443,991), we estimated associations between dietary contributions to GHG emissions and LU and all-cause and cause-specific mortality and incident cancers using Cox proportional-hazard regression models. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reduction in GHG emissions and LU, were estimated using counterfactual attributable fraction (AF) intervention models, simulating potential effects from dietary shifts based on the EAT-Lancet reference diet. Findings: There was an association between levels of dietary-based GHG emissions and LU and all-cause mortality, with a Hazard Ratio and 95% Confidence Interval (CI) of 1.13 (1.10, 1.16) and 1.18 (95% CI: 1.15, 1.21), respectively, comparing the fourth quartile to the first (HRQ4 vs Q1). Similar associations were observed for cause-specific mortality. There were also associations between overall cancer rates and GHG emissions (HRQ4 vs Q1: 1.11, 95% CI: 1.09, 1.14) and LU (HRQ4 vs Q1: 1.13, 95% CI: 1.10, 1.15); however, estimates differed by cancer type. Through counterfactual AF modelling of shifts in diets, we find that between 19 to 63% of deaths and 10 to 39% of cancers could be prevented, over a 20-year risk period, from adhering to different scores of the EAT-Lancet reference diet. Additionally, switching from a lower score of the EAT-Lancet reference diet to a higher score could reduce food-associated GHG and LU levels by 50% and 62%, respectively.Interpretation: Our results support shifts in diets that

Journal article

Vissers LET, Sluijs I, Burgess S, Forouhi NG, Freisling H, Imamura F, Nilsson TK, Renström F, Weiderpass E, Aleksandrova K, Dahm CC, Perez-Cornago A, Schulze MB, Tong TYN, Aune D, Bonet C, Boer JMA, Boeing H, Chirlaque MD, Conchi MI, Imaz L, Jäger S, Krogh V, Kyrø C, Masala G, Melander O, Overvad K, Panico S, Sánches MJ, Sonestedt E, Tjønneland A, Tzoulaki I, Verschuren WMM, Riboli E, Wareham NJ, Danesh J, Butterworth AS, van der Schouw YTet al., 2021, Milk intake and incident stroke and coronary heart disease in populations of European descent: A Mendelian Randomization study., Br J Nutr, Pages: 1-25

Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Journal article

Naghshi S, Aune D, Beyene J, Mobarak S, Asadi M, Sadeghi Oet al., 2021, Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies., BMJ, Vol: 375, Pages: n2213-n2213

OBJECTIVE: To examine the associations between dietary intake and tissue biomarkers of alpha linolenic acid (ALA) and risk of mortality from all causes, cardiovascular disease (CVD), and cancer. DESIGN: Systematic review and meta-analysis of prospective cohort studies. DATA SOURCES: PubMed, Scopus, ISI Web of Science, and Google Scholar to 30 April 2021. STUDY SELECTION: Prospective cohort studies that reported the risk estimates for death from all causes, CVD, and cancer. DATA SYNTHESIS: Summary relative risks and 95% confidence intervals were calculated for the highest versus lowest categories of ALA intake using random effects and fixed effects models. Linear and non-linear dose-response analyses were conducted to assess the dose-response associations between ALA intake and mortality. RESULTS: 41 articles from prospective cohort studies were included in this systematic review and meta-analysis, totalling 1 197 564 participants. During follow-up ranging from two to 32 years, 198 113 deaths from all causes, 62 773 from CVD, and 65 954 from cancer were recorded. High intake of ALA compared with low intake was significantly associated with a lower risk of deaths from all causes (pooled relative risk 0.90, 95% confidence interval 0.83 to 0.97, I2=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I2=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I2=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I2=3.8%, n=10). In the dose-response analysis, a 1 g/day increase in ALA intake (equivalent to one tablespoon of canola oil or 0.5 ounces of walnut) was associated with a 5% lower risk of all cause (0.95, 0.91 to 0.99, I2=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I2=30.7%, n=14). The pooled relative risks for the highest compared with lowest tissue levels of ALA indicated a significant inverse association with all cause mortality (0.95, 0.90 to 0.99, I2=8.2%, n=26). Also, based on the d

Journal article

Mahamat-Saleh Y, Fiolet T, Rebeaud ME, Mulot M, Guihur A, El Fatouhi D, Laouali N, Peiffer-Smadja N, Aune D, Severi Get al., 2021, Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies, BMJ OPEN, Vol: 11, ISSN: 2044-6055

Journal article

Mori N, Keski-Rahkonen P, Gicquiau A, Rinaldi S, Dimou N, Harlid S, Harbs J, Van Guelpen B, Aune D, Cross AJ, Tsilidis KK, Severi G, Kvaskoff M, Fournier A, Kaaks R, Fortner RT, Schulze MB, Jakszyn P, Sánchez M-J, Colorado-Yohar SM, Ardanaz E, Travis R, Watts EL, Masala G, Krogh V, Tumino R, Sacerdote C, Panico S, de-Mesquita BB, Gram IT, Waaseth M, Gunter MJ, Murphy Net al., 2021, Endogenous circulating sex hormone concentrations and colon cancer risk in postmenopausal women: a prospective study and meta-analysis, JNCI Cancer Spectrum, ISSN: 2515-5091

BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk. However, epidemiological studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone binding globulin (SHBG) with colon cancer risk in a nested case–control study of 1,028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were non-current users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a non-statistically significant positive relationship was found between circulating estrone and colon cancer risk (OR per log2-1 unit increment = 1.17, 95%CI = 1.00–1.38; ORquartile4-quartile1 = 1.33, 95%CI = 0.89–1.97, Ptrend = 0.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol, and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex horm

Journal article

Iguacel I, Perez-Cornago A, Schmidt JA, Van Puyvelde H, Travis R, Casagrande C, Nicolas G, Riboli E, Weiderpass E, Ardanaz E, Barricarte A, Bodén S, Bruno E, Ching-López A, Dagfinn A, Jensen TE, Ericson U, Johansson I, Ma Huerta J, Katzke V, Kühn T, Sacerdote C, Schulze MB, Skeie G, Ramne S, Ward H, Gunter MJ, Huybrechts Iet al., 2021, Evaluation of protein and amino acid intake estimates from the EPIC dietary questionnaires and 24-h dietary recalls using different food composition databases., Nutr Metab Cardiovasc Dis

BACKGROUND AND AIMS: This study aimed to expand the European Prospective Investigation into Cancer and Nutrition (EPIC) nutrient database (ENDB) by adding amino acid (AA) values, using the U.S. nutrient database (USNDB). Additionally, we aimed to evaluate these new protein and AA intake estimates from the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR) using different matching procedures. METHODS AND RESULTS: Dietary energy, protein and AA intakes were assessed via DQ and 24-HDR by matching with the USNDB food composition table. Energy and protein intakes calculated using USNDB matching were compared with those calculated using ENDB, that uses country specific food composition tables. Pearson correlations, Cohen's weighted kappa statistic and Bland-Altman plots were used to compare data resulting from USNDB matching with our reference from ENDB matching. Very high correlations were found when comparing daily energy (r = 0.99) and dietary protein intakes (r = 0.97) assessed via USNDB with those obtained via ENDB (matching for DQ and 24-HDR). Significant positive correlations were also found with energy and protein intakes acquired via 24-HDRs in the EPIC calibration sample. CONCLUSION: Very high correlations between total energy and protein intake obtained via the USDA matching and those available in ENDB suggest accuracy in the food matching. Individual AA have been included in the extended EPIC Nutrient database that will allow important analyses on AA disease prospective associations in the EPIC study.

Journal article

Mousavi SM, Jalilpiran Y, Karimi E, Aune D, Larijani B, Mozaffarian D, Willett WC, Esmaillzadeh Aet al., 2021, Dietary Intake of Linoleic Acid, Its Concentrations, and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies, DIABETES CARE, Vol: 44, Pages: 2173-2181, ISSN: 0149-5992

Journal article

Hockey M, Rocks T, Ruusunen A, Jacka FN, Huang W, Liao B, Aune D, Wang Y, Nie J, O'Neil Aet al., 2021, Psychological distress as a risk factor for all-cause, chronic disease- and suicide-specific mortality: a prospective analysis using data from the National Health Interview Survey, SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY, ISSN: 0933-7954

Journal article

Dos Santos M, Ferrari GL, Lee DH, Aune D, Wang Y, Giovannucci E, Rodrigues Matsudo VK, Machado Rezende LFet al., 2021, Patterns Of Recommended Levels Of Physical Activity And Mortality: A Prospective Cohort Study, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 192-193, ISSN: 0195-9131

Conference paper

Jeong GH, Grosso G, Aune D, Stubbs B, Koyanagi A, Cho E, Giovannucci EL, Shin JILet al., 2021, Reply to Yi M et al., Adv Nutr, Vol: 12, Pages: 1595-1596

Journal article

Ried-Larsen M, Rasmussen MG, Blond K, Overvad TF, Overvad K, Steindorf K, Katzke V, Andersen JLM, Petersen KEN, Aune D, Tsilidis KK, Heath AK, Papier K, Panico S, Masala G, Pala V, Weiderpass E, Freisling H, Bergmann MM, Verschuren WMM, Zamora-Ros R, Colorado-Yohar SM, Spijkerman AMW, Schulze MB, Ardanaz EMA, Andersen LB, Wareham N, Brage S, Grøntved Aet al., 2021, Association of cycling with all-cause and cardiovascular disease mortality among persons with diabetes. The European Prospective Investigation into Cancer and Nutrition (EPIC) study, JAMA Internal Medicine, ISSN: 2168-6106

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes.Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality.Design, Setting, and Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020.Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination.Main Outcomes and Measures The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors.Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of f

Journal article

Porta M, Gasull M, Pumarega J, Kiviranta H, Rantakokko P, Raaschou-Nielsen O, Bergdahl IA, Sandanger TM, Agudo A, Rylander C, Nøst TH, Donat-Vargas C, Aune D, Heath AK, Cirera L, Goñi-Irigoyen F, Alguacil J, Giménez-Robert À, Tjønneland A, Sund M, Overvad K, Mancini FR, Rebours V, Boutron-Ruault M-C, Kaaks R, Schulze MB, Trichopoulou A, Palli D, Grioni S, Tumino R, Naccarati A, Panico S, Vermeulen R, Quirós JR, Rodríguez-Barranco M, Colorado-Yohar SM, Chirlaque M-D, Ardanaz E, Wareham N, Key T, Johansson M, Murphy N, Ferrari P, Huybrechts I, Chajes V, Gonzalez CA, de-Mesquita BB, Gunter M, Weiderpass E, Riboli E, Duell EJ, Katzke V, Vineis Pet al., 2021, Plasma concentrations of persistent organic pollutants and pancreatic cancer risk, International Journal of Epidemiology, Pages: 1-12, ISSN: 0300-5771

BackgroundFindings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.MethodsWe conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.ResultsSome associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.ConclusionsIndividually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.

Journal article

Huang W, Aune D, Ferrari G, Zhang L, Lan Y, Nie J, Chen X, Xu D, Wang Y, Rezende LFMet al., 2021, Psychological distress and all-cause, cardiovascular disease, cancer mortality among adults with and without diabetes, Clinical Epidemiology, Vol: Volume 13, Pages: 555-565, ISSN: 1179-1349

Aim: To examine the association of psychological distress with all-cause, cardiovascular disease (CVD) and cancer mortality in US adults, and verified whether the associations differed between participants with and without diabetes.Methods: A total of 485,864 adults (446,288 without diabetes and 39,576 with diabetes) who participated in the National Health Interview Survey from 1997 to 2013 were linked to the National Death Index through December 31, 2015. Psychological distress was measured by the Kessler 6 distress scale (K6). Multivariable Cox proportional hazards regression models were performed to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between psychological distress and mortality.Results: We ascertained 11,746 deaths (mean follow-up, 7. 7 years) among people with diabetes and 51,636 deaths (9.9 years) among those without diabetes. Psychological distress was associated with higher all-cause, CVD, and cancer mortality. Compared to non-diabetic adults without psychological distress, HRs (95% CI) were 1.07 (1.04 to 1.09) for mild, 1.26 (1.22 to 1.30) for moderate and 1.46 (1.38 to 1.55) for severe psychological distress. Compared to the same reference group, in diabetic participants the HRs were 1.39 (1.33 to 1.44) for no psychological distress, 1.59 (1.53 to 1.66) for mild, 1.90 (1.80 to 2.00) for moderate and 1.98 (1.82 to 2.17) for severe psychological distress. Similar associations were also observed for CVD and cancer mortality but with non-statistically significant interaction.Conclusion: Psychological distress was associated with higher mortality, particularly in participants with diabetes. Strategies to ameliorate psychological distress may be important to reduce mortality in this population.

Journal article

Aune D, Huang W, Nie J, Wang Yet al., 2021, Hypertension and all-cause and cause-specific mortality: An outcome-wide association study of 67 causes of death in the National Health Interview Survey., BioMed Research International, Vol: 2021, Pages: 1-10, ISSN: 1110-7243

Background. Few studies have assessed the association between hypertension and risk of detailed causes of death. We investigatedthe association between hypertension and all-cause mortality and 67 causes of death in a large cohort. Methods. Multivariable Coxregression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertensionvs. no hypertension and mortality. Adults aged ≥18 years (n = 213798) were recruited in 1997-2004 and followed throughDecember 31, 2006. Results. During 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. nohypertension was associated with increased risk of all-cause mortality (HR = 1:25, 95% CI: 1.19-1.31) and mortality fromsepticemia (HR =1.66, 1.06-2.59), other infectious parasitic diseases (HR = 2:67, 1.09-6.51), diabetes mellitus (HR = 1:97, 1.45-2.67), circulatory disease (HR = 1:49, 1.37-1.61), hypertensive heart disease (HR = 3:23, 2.00-5.20), ischemic heart disease ðHR =1:35, 1.23-1.49), acute myocardial infarction (HR = 1:50, 1.27-1.77), other chronic ischemic heart diseases (HR = 1:35, 1.17-1.56), all other forms of heart disease (HR = 1:51, 1.21-1.89), primary hypertension and renal disease (HR = 3:11, 1.82-5.30),cerebrovascular disease (HR = 1:64, 1.37-1.97), other circulatory system diseases (HR = 1:71, 1.09-2.69), other chronic lowerrespiratory diseases (HR = 1:39, 1.12-1.73), other chronic liver disease (HR = 1:89, 1.06-3.37), renal failure (HR = 1:91, 1.33-2.74), motor vehicle accidents (HR = 1:60, 1.07-2.37), and all other diseases (HR =1.30, 1.10-1.54), but with lower risk of uterinecancer (HR = 0:37, 95% CI: 0.15-0.90) and Alzheimer’s disease (HR = 0:65, 95% CI: 0.47-0.92). Conclusion. Hypertension wasassociated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatorydisease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies ar

Journal article

Agudo A, Cayssials V, Bonet C, Tjønneland A, Overvad K, Boutron-Ruault M-C, Affret A, Fagherazzi G, Katzke V, Schubel R, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Grioni S, Tumino R, Ricceri F, Panico S, Bueno-de-Mesquita B, Peeters PH, Weiderpass E, Skeie G, Nøst TH, Lasheras C, Rodríguez-Barranco M, Amiano P, Chirlaque M-D, Ardanaz E, Ohlsson B, Dias JA, Nilsson LM, Myte R, Khaw K-T, Perez-Cornago A, Gunter M, Huybrechts I, Cross AJ, Tsilidis K, Riboli E, Jakszyn Pet al., 2021, Inflammatory potential of the diet & risk of gastric cancer in the European Investigation into Cancer & Nutrition, American Journal of Clinical Nutrition, Vol: 36, Pages: 953-964, ISSN: 1938-3207

The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.

Journal article

Aune D, Sen A, Norat T, Riboli E, Folseraas Tet al., 2021, Primary sclerosing cholangitis and the risk of cancer, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of cohort studies, Scientific Reports, Vol: 11, ISSN: 2045-2322

A diagnosis of primary sclerosing cholangitis (PSC) has been associated with increased risk of hepatobiliary cancers, colorectal cancer and all-cause mortality in several studies, while associations with cardiovascular disease have been inconsistent. We conducted a systematic review and meta-analysis of published cohort studies on the topic to summarize these associations. PubMed and Embase databases were searched up to January 13th, 2020. Cohort studies on PSC and risk of cancer, cardiovascular disease, or mortality were included. Summary relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using random effects models. The summary RR (95% CI) comparing persons with PSC to persons without PSC was 584.37 (269.42–1267.51, I2 = 89%, n = 4) for cholangiocarcinoma (CCA), 155.54 (125.34–193.02, I2 = 0%, n = 3) for hepatobiliary cancer, 30.22 (11.99–76.17, I2 = 0%, n = 2) for liver cancer, 16.92 (8.73–32.78, I2 = 88%, n = 4) for gastrointestinal cancer, 7.56 (2.42–23.62, I2 = 0%, n = 3) for pancreatic cancer, 6.10 (4.19–8.87, I2 = 14%, n = 7) for colorectal cancer (CRC), 4.13 (2.99–5.71, I2 = 80%, n = 5) for total cancer, 3.55 (2.94–4.28, I2 = 46%, n = 5) for all-cause mortality, and 1.57 (0.25–9.69, I2 = 79%, n = 2) for cardiovascular disease. Strong positive associations were observed between PSC and risk of CCA, hepatobiliary cancer, liver cancer, gastrointestinal cancer, pancreatic cancer, CRC, total cancer, and all-cause mortality, but not for cardiovascular disease.

Journal article

Mayen A-L, Aglago EK, Knaze V, Cordova R, Schalkwijk CG, Wagner K-H, Aleksandrova K, Fedirko V, Keski-Rahkonen P, Leitzmann MF, Katzke V, Srour B, Schulze MB, Masala G, Krogh V, Panico S, Tumino R, Bueno-de-Mesquita B, Brustad M, Agudo A, Chirlaque Lopez MD, Amiano P, Ohlsson B, Ramne S, Aune D, Weiderpass E, Jenab M, Freisling Het al., 2021, Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study, INTERNATIONAL JOURNAL OF CANCER, Vol: 149, Pages: 854-864, ISSN: 0020-7136

Journal article

Halvorsen RE, Elvestad MP, Molin M, Aune Det al., 2021, Fruit and vegetable consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective studies, BMJ Nutrition, Prevention & Health, ISSN: 2516-5542

Background: The association between intake of fruit and vegetables and their subtypes, and the risk of type 2 diabetes has been investigated in several studies, but the results have been inconsistent. Objective: We conducted an updated systematic review and dose-response meta-analysis of prospective studies on intakes of fruit and vegetables and fruit and vegetable subtypes and the risk of type 2 diabetes.Design: PubMed and Embase databases were searched up to 20th of October 2020. Prospective cohort studies of fruit and vegetable consumption and type 2 diabetes mellitus were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random effects model.Results: We included 23 cohort studies. The summary RR for high vs. low intake and per 200 g/day were 0.93 (95% CI: 0.89-0.98, I2 = 0%, n = 10 studies) and 0.98 (95% CI: 0.95-1.01, I2 = 37.8%, n = 7) for fruit and vegetables combined, 0.93 (95% CI: 0.90-0.97, I2 = 9.3%, n = 20) and 0.96 (95% CI: 0.92-1.00, I2 = 68.4%, n = 19) for fruits, and 0.95 (95% CI: 0.88-1.02, I2 = 60.4%, n = 17) and 0.97 (95% CI: 0.94-1.01, I2 = 39.2%, n = 16) for vegetables, respectively. Inverse associations were observed for apples, apples and pears, blueberries, grapefruit and grapes and raisins, while positive associations were observed for intakes of cantaloupe, fruit drinks, fruit juice, watermelon, brussels sprouts, cauliflower, kale, mustard and chard greens and potatoes, however, most of these associations were based on few studies and need further investigation in additional studies.Conclusions: This meta-analysis found a weak inverse association between fruit and vegetable intake and type 2 diabetes risk. There is indication of both inverse and positive associations between intake of several fruit and vegetables subtypes and type 2 diabetes risk, however, further studies are needed before firm conclusions can be made.

Journal article

Aune D, Schlesinger S, Leitzmann MF, Tonstad S, Norat T, Riboli E, Vatten LJet al., 2021, Physical activity and the risk of heart failure: a systematic review and dose–response meta-analysis of prospective studies, European Journal of Epidemiology, Vol: 36, Pages: 367-381, ISSN: 0393-2990

Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70–0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68–0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59–0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69–0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86–0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19–0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose–response analyses, the summary RRs were 0.89 (95% CI 0.83–0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65–0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose–response curve at 15–20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activi

Journal article

Matta M, Huybrechts I, Biessy C, Casagrande C, Yammine S, Fournier A, Olsen KS, Lukic M, Gram IT, Ardanaz E, Sánchez M-J, Dossus L, Fortner RT, Srour B, Jannasch F, Schulze MB, Amiano P, Agudo A, Colorado-Yohar S, Quirós JR, Tumino R, Panico S, Masala G, Pala V, Sacerdote C, Tjønneland A, Olsen A, Dahm CC, Rosendahl AH, Borgquist S, Wennberg M, Heath AK, Aune D, Schmidt J, Weiderpass E, Chajes V, Gunter MJ, Murphy Net al., 2021, Dietary intake of trans fatty acids and breast cancer risk in 9 European countries, BMC Medicine, Vol: 19, Pages: 1-11, ISSN: 1741-7015

BackgroundTrans 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.MethodsIn 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.ResultsAfter 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 bre

Journal article

Nie J, O'Neil A, Liao B, Lu C, Aune D, Wang Yet al., 2021, Risk factors for completed suicide in the general population: A prospective cohort study of 242, 952 people, JOURNAL OF AFFECTIVE DISORDERS, Vol: 282, Pages: 707-711, ISSN: 0165-0327

Journal article

Lee DH, Rezende LFM, Ferrari G, Aune D, Keum N, Tabung FK, Giovannucci ELet al., 2021, Physical activity and all-cause and cause-specific mortality: assessing the impact of reverse causation and measurement error in two large prospective cohorts, European Journal of Epidemiology, Vol: 36, Pages: 275-285, ISSN: 0393-2990

Most cohort studies have only a single physical activity (PA) measure and are thus susceptible to reverse causation and measurement error. Few studies have examined the impact of these potential biases on the association between PA and mortality. A total of 133,819 participants from Nurses’ Health Study and Health Professionals Follow-up Study (1986–2014) reported PA through biennial questionnaires. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for PA and mortality using different analytic approaches comparing single (baseline, simple update = most recent) versus repeated (cumulative average) measures of PA and applying various lag times separating PA measurement and time at risk. Over 3.2 million person-years, we documented 47,273 deaths. The pooled multivariable-adjusted HR (95% CI) of all-cause mortality per 10 MET-hour/week was 0.95 (0.94–0.96) for baseline PA, 0.78 (0.77–0.79) for simple updated PA and 0.87 (0.86–0.88) for cumulative average PA in the range of 0–50 MET-hour/week. Simple updated PA showed the strongest inverse association, suggesting larger impact of reverse causation. Application of 2-year lag substantially reduced the apparent reverse causation (0.85 (0.84–0.86) for simple updated PA and 0.90 (0.89–0.91) for cumulative average PA), and 4–12-year lags had minimal additional effects. In the dose–response analysis, baseline or simple updated PA showed a J or U-shaped association with all-cause mortality while cumulative average PA showed an inverse association across a wide range of PA (0–150 MET-hour/week). Similar findings were observed for different specific mortality causes. In conclusion, PA measured at baseline or with short lag time was prone to bias. Cumulative average PA showed robust evidence that PA is inversely associated with mortality in a dose-response manner.

Journal article

Perez-Cornago A, Crowe FL, Appleby PN, Bradbury KE, Wood AM, Jakobsen MU, Johnson L, Sacerdote C, Steur M, Weiderpass E, Würtz AML, Kühn T, Katzke V, Trichopoulou A, Karakatsani A, La Vecchia C, Masala G, Tumino R, Panico S, Sluijs I, Skeie G, Imaz L, Petrova D, Quirós JR, Yohar SMC, Jakszyn P, Melander O, Sonestedt E, Andersson J, Wennberg M, Aune D, Riboli E, Schulze MB, di Angelantonio E, Wareham NJ, Danesh J, Forouhi NG, Butterworth AS, Key TJet al., 2021, Plant foods, dietary fibre and risk of ischaemic heart disease in the European prospective investigation into cancer and nutrition (EPIC) cohort, International Journal of Epidemiology, Vol: 50, Pages: 212-222, ISSN: 0300-5771

BACKGROUND: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. RESULTS: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. CONCLUSIONS: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.

Journal article

Soltani S, Abdollahi S, Aune D, Jayedi Aet al., 2021, Body mass index and cancer risk in patients with type 2 diabetes: a dose-response meta-analysis of cohort studies, Scientific Reports, Vol: 11, ISSN: 2045-2322

Although obesity has been associated with an increased cancer risk in the general population, the association in patients with type 2 diabetes (T2D) remains controversial. We conducted a dose–response meta-analysis of cohort studies of body mass index (BMI) and the risk of total and site-specific cancers in patients with T2D. A systematic literature search was conducted in PubMed, Scopus, and Medline until September 2020 for cohort studies on the association between BMI and cancer risk in patients with T2D. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. Ten prospective and three retrospective cohort studies (3,345,031 participants and 37,412 cases) were included in the meta-analysis. Each 5-unit increase in BMI (kg/m2) was associated with a 6% higher risk of total cancer (RR: 1.06, 95% CI 1.01, 1.10; I2 = 55.4%, n = 6), and with a 12% increased risk in the analysis of breast cancer (RR: 1.12, 95% CI 1.05, 1.20; I2 = 0%, n = 3). The pooled RRs showed no association with prostate cancer (RR: 1.02, 95% CI 0.92, 1.13; I2 = 64.6%, n = 4), pancreatic cancer (RR: 0.97, 95% CI 0.84, 1.11; I2 = 71%, n = 3), and colorectal cancer (RR: 1.05, 95% CI 0.98, 1.13; I2 = 65.9%, n = 2). There was no indication of nonlinearity for total cancer (Pnon-linearity = 0.99), however, there was evidence of a nonlinear association between BMI and breast cancer (Pnon-linearity = 0.004) with steeper increases in risk from a BMI around 35 and above respectively. Higher BMI was associated with a higher risk of total, and breast cancer but not with risk of other cancers, in patients with T2D, however, further studies are needed before firm conclusions can be drawn.

Journal article

Ellingjord-Dale M, Papadimitriou N, Katsoulis M, Yee C, Dimou N, Gill D, Aune D, Ong J-S, MacGregor S, Elsworth B, Lewis SJ, Martin RM, Riboli E, Tsilidis KKet al., 2021, Coffee consumption and risk of breast cancer: A Mendelian randomization study, PLoS One, Vol: 16, ISSN: 1932-6203

Background:Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer.Methods:We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations.Results:One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80–1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79–1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75–1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80–1.25), weighted median (OR: 0.97, 95% CI: 0.89–1.05) and weighted mode (OR: 1.00, CI: 0.93–1.07).Conclusions:The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.

Journal article

Zamora-Ros R, Lujan-Barroso L, Achaintre D, Franceschi S, Kyro C, Overvad K, Tjonneland A, Truong T, Lecuyer L, Boutron-Ruault M-C, Katzke V, Johnson TS, Schulze MB, Trichopoulou A, Peppa E, La Vechia C, Masala G, Pala V, Panico S, Tumino R, Ricceri F, Skeie G, Quiros JR, Rodriguez-Barranco M, Amiano P, Chirlaque M-D, Ardanaz E, Almquist M, Hennings J, Vermeulen R, Wareham NJ, Tong TYN, Aune D, Byrnes G, Weiderpass E, Scalbert A, Rinaldi S, Agudo Aet al., 2021, Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 113, Pages: 162-171, ISSN: 0002-9165

Journal article

Rothwell JA, Murphy N, Bešević J, Kliemann N, Jenab M, Ferrari P, Achaintre D, Gicquiau A, Vozar B, Scalbert A, Huybrechts I, Freisling H, Prehn C, Adamski J, Cross AJ, Pala VM, Boutron-Ruault M-C, Dahm CC, Overvad K, Gram IT, Sandanger TM, Skeie G, Jakszyn P, Tsilidis KK, Aleksandrova K, Schulze MB, Hughes DJ, van Guelpen B, Bodén S, Sánchez M-J, Schmidt JA, Katzke V, Kühn T, Colorado-Yohar S, Tumino R, Bueno-de-Mesquita B, Vineis P, Masala G, Panico S, Eriksen AK, Tjønneland A, Aune D, Weiderpass E, Severi G, Chajès V, Gunter MJet al., 2020, Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort, Clinical Gastroenterology and Hepatology, ISSN: 1542-3565

Background & AimsColorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer cohort.MethodsScores reflecting adherence to the WCRF/AICR recommendations (scale, 1–5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.ResultsHigher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29–0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50–0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86–1.00) overall. Signature associations were stronger in male compared with female participants.ConclusionsMetabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

Journal article

Aune D, Sen A, Kobeissi E, Hamer M, Norat T, Riboli Eet al., 2020, Physical activity and the risk of abdominal aortic aneurysm: a systematic review and meta-analysis of prospective studies, Scientific Reports, Vol: 10, Pages: 1-10, ISSN: 2045-2322

The association between physical activity and risk of abdominal aortic aneurysm has been inconsistent with some studies reporting a reduced risk while others have found no association. We conducted a systematic review and meta-analysis of prospective studies to quantify the association. PubMed and Embase databases were searched up to 3 October 2020. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of abdominal aortic aneurysm associated with physical activity. Summary RRs (95% CIs) were estimated using a random effects model. Nine prospective studies (2073 cases, 409732 participants) were included. The summary RR for high vs. low physical activity was 0.70 (95% CI: 0.56-0.87, I2=58%) and per 20 metabolic equivalent task (MET)-hours/week increase of activity was 0.84 (95% CI: 0.74-0.95, I2=59%, n=6). Although the test for nonlinearity was not significant (p=0.09) the association appeared to be stronger when increasing the physical activity level from 0 to around 20-25 MET-hours/week than at higher levels. The current meta-analysis suggest that higher physical activity may reduce the risk of abdominal aortic aneurysm, however, further studies are needed to clarify the dose-response relationship between different subtypes and intensities of activity and abdominal aortic aneurysm risk.

Journal article

Berlanga A, Cupp M, Tzoulaki I, Evangelou E, Aune D, Cariolou Met al., 2020, Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies, BMC Medicine, Vol: 18, ISSN: 1741-7015

BackgroundAlthough neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.MethodsWe searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria.ResultsA total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence.ConclusionIn total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility.

Journal article

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