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

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192 results found

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, 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, ISSN: 1110-7243

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, ISSN: 1938-3207

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

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

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

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

Ibsen DB, Steur M, Imamura F, Overvad K, Schulze MB, Bendinelli B, Guevara M, Agudo A, Amiano P, Aune D, Barricarte A, Ericson U, Fagherazzi G, Franks PW, Freisling H, Quiros JR, Grioni S, Heath AK, Huybrechts I, Katze V, Laouali N, Mancini F, Masala G, Olsen A, Papier K, Ramne S, Rolandsson O, Sacerdote C, Sanchez M-J, Santiuste C, Simeon V, Spijkerman AMW, Srour B, Tjonneland A, Tong TYN, Tumino R, van der Schouw YT, Weiderpass E, Wittenbecher C, Sharp SJ, Riboli E, Forouhi NG, Wareham NJet al., 2020, Replacement of red and processed meat with other food sources of protein and the risk of type 2 diabetes in European populations: The EPIC-interAct study, Diabetes Care, Vol: 43, Pages: 2660-2667, ISSN: 0149-5992

OBJECTIVE There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.RESULTS There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83–0.97) (30 g/day), yogurt (0.90, 0.86–0.95) (70 g/day), nuts (0.90, 0.84–0.96) (10 g/day), or cereals (0.92, 0.88–0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.CONCLUSIONS Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.

Journal article

Kim TL, Jeong GH, Yang JW, Lee KH, Kronbichler A, van der Vliet HJ, Grosso G, Galvano F, Aune D, Kim JY, Veronese N, Stubbs B, Solmi M, Koyanagi A, Hong SH, Dragioti E, Cho E, de Rezende LFM, Giovannucci EL, Il Shin J, Gamerith Get al., 2020, Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies, ADVANCES IN NUTRITION, Vol: 11, Pages: 1437-1452, ISSN: 2161-8313

Journal article

Naudin S, Viallon V, Hashim D, Freisling H, Jenab M, Weiderpass E, Perrier F, McKenzie F, Bueno-de-Mesquita HB, Olsen A, Tjønneland A, Dahm CC, Overvad K, Mancini FR, Rebours V, Boutron-Ruault M-C, Katzke V, Kaaks R, Bergmann M, Boeing H, Peppa E, Karakatsani A, Trichopoulou A, Pala V, Masala G, Panico S, Tumino R, Sacerdote C, May AM, van Gils CH, Rylander C, Borch KB, Chirlaque López MD, Sánchez M-J, Ardanaz E, Quirós JR, Amiano Exezarreta P, Sund M, Drake I, Regnér S, Travis RC, Wareham N, Aune D, Riboli E, Gunter MJ, Duell EJ, Brennan P, Ferrari Pet al., 2020, Healthy lifestyle and the risk of pancreatic cancer in the EPIC study, European Journal of Epidemiology, Vol: 35, Pages: 975-986, ISSN: 0393-2990

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

Journal article

Ohno T, Aune D, Heath A, 2020, Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies, Scientific Reports, Vol: 10, Pages: 1-12, ISSN: 2045-2322

ABSTRACTBackground: Several studies have investigated associations between overweight/obesity and risk of developing rheumatoid arthritis, however, the evidence is not entirely consistent, and previous meta-analyses mainly included case-control studies, which can be affected by various biases. We therefore conducted a systematic review and meta-analysis of cohort studies on adiposity and risk of rheumatoid arthritis. Methods: Relevant studies were identified by searching PubMed and Embase databases. Random effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for rheumatoid arthritis in relation to different measures of adiposity. Results: Thirteen cohort studies (10 publications) were included. The summary RR per 5 kg/m2 increase in BMI was 1.11 (95% CI: 1.05-1.18, I2=50%), but the association was restricted to women (1.15, 95% CI: 1.08-1.21, I2=17%) and not observed in men (0.89, 95% CI: 0.73-1.09, I2=58%). The summary RR per 5 kg/m2 increment in BMI at age 18 years was 1.17 (95% CI: 1.01-1.36, I2=26%, n=3), and per 10 cm increase in waist circumference was 1.13 (95% CI: 1.02-1.25, I2=44%, n=2). Conclusions: Higher BMI in middle age, BMI at age 18 years, and waist circumference were associated with increased rheumatoid arthritis risk, suggesting adiposity could be targeted for primary prevention.

Journal article

Naudin S, Margalef MS, Hosnijeh FS, Nieters A, Kyro C, Tjonneland A, Dahm CC, Overvad K, Mahamat-Saleh Y, Besson C, Boutron-Ruault M-C, Kuehn T, Canzian F, Schulze MB, Peppa E, Karakatsani A, Trichopoulou A, Sieri S, Masala G, Panico S, Tumino R, Ricceri F, Chen SLF, Barroso LL, Huerta JM, Sanchez M-J, Ardanaz E, Menendez V, Exezarreta PA, Spaeth F, Jerkeman M, Jirstom K, Schmidt JA, Aune D, Weiderpass E, Riboli E, Vermeulen R, Casabonne D, Gunter M, Brennan P, Ferrari Pet al., 2020, Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study, International Journal of Cancer, Vol: 147, Pages: 1649-1656, ISSN: 0020-7136

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

Journal article

Christakoudi S, Tsilidis KK, Muller DC, Freisling H, Weiderpass E, Overvad K, Söderberg S, Häggström C, Pischon T, Dahm CC, Zhang J, Tjønneland A, Halkjær J, MacDonald C, Boutron-Ruault M-C, Mancini FR, Kühn T, Kaaks R, Schulze MB, Trichopoulou A, Karakatsani A, Peppa E, Masala G, Pala V, Panico S, Tumino R, Sacerdote C, Quirós JR, Agudo A, Sánchez M-J, Cirera L, Barricarte-Gurrea A, Amiano P, Memarian E, Sonestedt E, Bueno-de-Mesquita B, May AM, Khaw K-T, Wareham NJ, Tong TYN, Huybrechts I, Noh H, Aglago EK, Ellingjord-Dale M, Ward HA, Aune D, Riboli Eet al., 2020, ABSI (A Body Shape Index) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort, Scientific Reports, Vol: 10, ISSN: 2045-2322

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m2) or obese (BMI≥30 kg/m2) categories, while the highest quartile of ABSI separated 18%-39% of the individuals within each BMI category, which had 22%-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.

Journal article

Bueno-de-Mesquita B, Cross A, Aune D, Tsilidis Ket al., 2020, Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses, BMC Medicine, Vol: 18, Pages: 1-15, ISSN: 1741-7015

BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported antioxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5x10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity=0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin, were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P=0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P=0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were

Journal article

Yammine S, Huybrechts I, Biessy C, Dossus L, Aglago EK, Naudin S, Ferrari P, Weiderpass E, Tjonneland A, Hansen L, Overvad K, Mancini FR, Boutron-Ruault M-C, Kvaskoff M, Fortner RT, Kaaks R, Schulze MB, Boeing H, Trichopoulou A, Karakatsani A, La Vecchia C, Benetou V, Masala G, Krogh V, Mattiello A, Macciotta A, Gram IT, Skeie G, Quiros JR, Agudo A, Sanchez M-J, Chirlaque M-D, Ardanaz E, Gil L, Sartor H, Drake I, Idahl A, Lundin E, Aune D, Ward H, Merritt MA, Allen NE, Gunter MJ, Chajes Vet al., 2020, Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 29, Pages: 1739-1749, ISSN: 1055-9965

Journal article

Hosnijeh FS, Kolijn PM, Casabonne D, Nieters A, Solans M, Naudin S, Ferrari P, Mckay JD, Weiderpass E, Perduca V, Besson C, Mancini FR, Masala G, Krogh V, Ricceri F, Huerta JM, Petrova D, Sala N, Trichopoulou A, Karakatsani A, La Vecchia C, Kaaks R, Canzian F, Aune D, Boeing H, Schulze MB, Perez-Cornago A, Langerak AW, van der Velden VHJ, Vermeulen Ret al., 2020, Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development, Scientific Reports, Vol: 10, Pages: 1-12, ISSN: 2045-2322

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case–control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

Journal article

Mahamat-Saleh Y, Aune D, Schlesinger S, 2020, 25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies, Scientific Reports, Vol: 10, Pages: 1-15, ISSN: 2045-2322

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose–response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose–response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17–1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13–1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19–1.67), and 1.57 (0.64–3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.

Journal article

Kliemann N, Murphy N, Viallon V, Freisling H, Tsilidis KK, Rinaldi S, Mancini FR, Fagherazzi G, Boutron-Ruault M-C, Boeing H, Schulze MB, Masala G, Krogh V, Sacerdote C, Santucci de Magistris M, Bueno-de-Mesquita B, Weiderpass E, Kühn T, Kaaks R, Jakszyn P, Redondo-Sánchez D, Amiano P, Chirlaque M-D, Barricarte Gurrea A, Ericson U, Drake I, Nøst TH, Aune D, May AM, Tjønneland A, Dahm CC, Overvad K, Tumino R, Ramón Quirós J, Trichopoulou A, Karakatsani A, La Vecchia C, Nilsson LM, Riboli E, Huybrechts I, Gunter MJet al., 2020, Predicted Basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition (Epic), International Journal of Cancer, Vol: 147, Pages: 648-661, ISSN: 0020-7136

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of estimated BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition. Estimated BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (Hazard Ratio per 1-standard deviation change in BMR [HR1-sd ]: 2.46; 95%CI 1.20; 5.03), and distal colon cancer (HR1-sd : 1.33; 95%CI 1.001; 1.77) among men, and with proximal colon (HR1-sd : 1.16; 95%CI 1.01; 1.35), pancreatic (HR1-sd : 1.37; 95%CI 1.13; 1.66), thyroid (HR1-sd : 1.65; 95%CI 1.33; 2.05), postmenopausal breast (HR1-sd : 1.17; 95%CI 1.11; 1.22), and endometrial (HR1-sd : 1.20; 95%CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness. This article is protected by copyright. All rights reserved.

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