Publications by authors named "Dagfinn Aune"

166 Publications

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 2021 Oct 13;375:n2213. Epub 2021 Oct 13.

Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

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, I=77.8%, 15 studies), CVD (0.92, 0.86 to 0.99, I=48.2%, n=16), and coronary heart disease (CHD) (0.89, 0.81 to 0.97, I=5.6%, n=9), and a slightly higher risk of cancer mortality (1.06, 1.02 to 1.11, I=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, I=76.2%, n=12) and CVD mortality (0.95, 0.91 to 0.98, I=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, I=8.2%, n=26). Also, based on the dose-response analysis, each 1 standard deviation increment in blood concentrations of ALA was associated with a lower risk of CHD mortality (0.92, 0.86 to 0.98, I=37.1%, n=14).

Conclusions: The findings show that dietary ALA intake is associated with a reduced risk of mortality from all causes, CVD, and CHD, and a slightly higher risk of cancer mortality, whereas higher blood levels of ALA are associated with a reduced risk of all cause and CHD mortality only.

Systematic Review Registration: PROSPERO CRD42021229487.
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http://dx.doi.org/10.1136/bmj.n2213DOI Listing
October 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 2021 Sep 20;44(9):2173-2181. Epub 2021 Aug 20.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

Background: Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting.

Purpose: To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population.

Data Sources: Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals.

Study Selection: We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults.

Data Synthesis: The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; = 66.2%). The certainty of the evidence was assessed as moderate.

Limitations: A limitation of our work was the observational design of studies included in the analyses.

Conclusions: We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.
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http://dx.doi.org/10.2337/dc21-0438DOI Listing
September 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 2021 Sep 20;44(9):2173-2181. Epub 2021 Aug 20.

Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

Background: Earlier evidence on the association between dietary polyunsaturated fatty acids and risk of diabetes has been conflicting.

Purpose: To quantitatively summarize previous studies on the association between dietary LA intake, its biomarkers, and the risk of type 2 diabetes mellitus (T2DM) in the general population.

Data Sources: Our data sources included PubMed/MEDLINE, Scopus, and ISI Web of Science until 24 October 2020; reference lists of all related articles; and key journals.

Study Selection: We included prospective cohort studies that examined the associations of linoleic acid (LA) with the risk of T2DM in adults.

Data Synthesis: The inverse variance method was applied to calculate summary relative risk (RR) of LA intake and its biomarkers, and dose-response associations were modeled using restricted cubic splines. Twenty-three publications, covering a total of 31 prospective cohorts, were included; these studies included 297,685 participants (22,639 incident diabetes cases) with dietary intake assessment and 84,171 participants (18,458 incident diabetes cases) with biomarker measurements. High intake of LA was associated with a 6% lower risk of T2DM (summary relative risk [RR] 0.94, 95% CI 0.90, 0.99; = 48.5%). In the dose-response analysis, each 5% increment in energy from LA intake was associated with a 10% lower risk of T2DM. There was also evidence of a linear association between LA intake and diabetes, with the lowest risk at highest intakes. The summary RR for diabetes per SD increment in LA concentrations in adipose tissue/blood compartments was 0.85 (95% CI 0.80, 0.90; = 66.2%). The certainty of the evidence was assessed as moderate.

Limitations: A limitation of our work was the observational design of studies included in the analyses.

Conclusions: We found that a high intake of dietary LA and elevated concentrations of LA in the body were both significantly associated with a lower risk of T2DM. These findings support dietary recommendations to consume dietary LA.
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http://dx.doi.org/10.2337/dc21-0438DOI Listing
September 2021

Hypertension and the Risk of All-Cause and Cause-Specific Mortality: An Outcome-Wide Association Study of 67 Causes of Death in the National Health Interview Survey.

Biomed Res Int 2021 12;2021:9376134. Epub 2021 Jul 12.

Department of Epidemiology and Biostatistics, School of Health Sciences, Wuhan University, Wuhan, China.

Background: Few studies have assessed the association between hypertension and risk of detailed causes of death. We investigated the association between hypertension and all-cause mortality and 67 causes of death in a large cohort.

Methods: Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertension vs. no hypertension and mortality. Adults aged ≥18 years ( = 213798) were recruited in 1997-2004 and followed through December 31, 2006.

Results: During 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. no hypertension was associated with increased risk of all-cause mortality (HR = 1.25, 95% CI: 1.19-1.31) and mortality from septicemia (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 (HR = 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 lower respiratory 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 uterine cancer (HR = 0.37, 95% CI: 0.15-0.90) and Alzheimer's disease (HR = 0.65, 95% CI: 0.47-0.92).

Conclusion: Hypertension was associated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatory disease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies are needed to clarify associations with less common causes of death and potential causality across outcomes.
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http://dx.doi.org/10.1155/2021/9376134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292050PMC
September 2021

Reply to Yi M et al.

Adv Nutr 2021 07;12(4):1595-1596

Division of Pediatric Nephrology, Severance Children's Hospital, Seoul, Republic of Korea.

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http://dx.doi.org/10.1093/advances/nmab043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321832PMC
July 2021

Psychological Distress and All-Cause, Cardiovascular Disease, Cancer Mortality Among Adults with and without Diabetes.

Clin Epidemiol 2021 13;13:555-565. Epub 2021 Jul 13.

Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, Sao Paulo, Brazil.

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.
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http://dx.doi.org/10.2147/CLEP.S308220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286108PMC
July 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 Intern Med 2021 Sep;181(9):1196-1205

University of Southern Denmark, Odense, Denmark.

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 follow-up, a total of 975 deaths from all causes were recorded. Compared with people who reported no cycling at both examinations, the multivariable-adjusted hazard ratios for all-cause mortality were 0.90 (95% CI, 0.71-1.14) in those who cycled and then stopped, 0.65 (95% CI, 0.46-0.92) in initial noncyclists who started cycling, and 0.65 (95% CI, 0.53-0.80) for people who reported cycling at both examinations. Similar results were observed for CVD mortality.

Conclusion And Relevance: In this cohort study, cycling was associated with lower all-cause and CVD mortality risk among people with diabetes independent of practicing other types of physical activity. Participants who took up cycling between the baseline and second examination had a considerably lower risk of both all-cause and CVD mortality compared with consistent noncyclists.
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http://dx.doi.org/10.1001/jamainternmed.2021.3836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290339PMC
September 2021

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk.

Int J Epidemiol 2021 Jul 14. Epub 2021 Jul 14.

Cancer Registry and Histopathology Department, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.

Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.

Methods: We 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.

Results: Some 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.

Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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http://dx.doi.org/10.1093/ije/dyab115DOI Listing
July 2021

Inflammatory potential of the diet and risk of breast cancer in the European Investigation into Cancer and Nutrition (EPIC) study.

Eur J Epidemiol 2021 Sep 20;36(9):953-964. Epub 2021 Jun 20.

Director Office, International Agency for Research on Cancer, World Health Organization, Lyon, France.

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.
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http://dx.doi.org/10.1007/s10654-021-00772-2DOI Listing
September 2021

Primary sclerosing cholangitis and the risk of cancer, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of cohort studies.

Sci Rep 2021 05 20;11(1):10646. Epub 2021 May 20.

Division of Surgery, Inflammatory Medicine and Transplantation, Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.

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, I = 89%, n = 4) for cholangiocarcinoma (CCA), 155.54 (125.34-193.02, I = 0%, n = 3) for hepatobiliary cancer, 30.22 (11.99-76.17, I = 0%, n = 2) for liver cancer, 16.92 (8.73-32.78, I = 88%, n = 4) for gastrointestinal cancer, 7.56 (2.42-23.62, I = 0%, n = 3) for pancreatic cancer, 6.10 (4.19-8.87, I = 14%, n = 7) for colorectal cancer (CRC), 4.13 (2.99-5.71, I = 80%, n = 5) for total cancer, 3.55 (2.94-4.28, I = 46%, n = 5) for all-cause mortality, and 1.57 (0.25-9.69, I = 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.
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http://dx.doi.org/10.1038/s41598-021-90175-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137938PMC
May 2021

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Int J Cancer 2021 Apr 25. Epub 2021 Apr 25.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, N -[carboxymethyl]lysine (CML), N -[1-carboxyethyl]lysine (CEL) and N -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-  = 0.87, 95% CI: 0.76-0.99, HR-  = 0.84, 95% CI: 0.74-0.96 and HR-  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-  = 1.28, 95% CI: 1.05-1.56, HR-  = 1.17; 95% CI: 0.96-1.40, HR-  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.
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http://dx.doi.org/10.1002/ijc.33612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360042PMC
April 2021

Dietary intake of trans fatty acids and breast cancer risk in 9 European countries.

BMC Med 2021 03 30;19(1):81. Epub 2021 Mar 30.

Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.

Background: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted.

Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors.

Results: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes.

Conclusions: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.
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http://dx.doi.org/10.1186/s12916-021-01952-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008592PMC
March 2021

Body mass index and cancer risk in patients with type 2 diabetes: a dose-response meta-analysis of cohort studies.

Sci Rep 2021 01 28;11(1):2479. Epub 2021 Jan 28.

Food Safety Research Center (Salt), Semnan University of Medical Sciences, Semnan, Iran.

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/m) was associated with a 6% higher risk of total cancer (RR: 1.06, 95% CI 1.01, 1.10; I = 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; I = 0%, n = 3). The pooled RRs showed no association with prostate cancer (RR: 1.02, 95% CI 0.92, 1.13; I = 64.6%, n = 4), pancreatic cancer (RR: 0.97, 95% CI 0.84, 1.11; I = 71%, n = 3), and colorectal cancer (RR: 1.05, 95% CI 0.98, 1.13; I = 65.9%, n = 2). There was no indication of nonlinearity for total cancer (P = 0.99), however, there was evidence of a nonlinear association between BMI and breast cancer (P = 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.
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http://dx.doi.org/10.1038/s41598-021-81671-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844243PMC
January 2021

Coffee consumption and risk of breast cancer: A Mendelian randomization study.

PLoS One 2021 19;16(1):e0236904. Epub 2021 Jan 19.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236904PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815134PMC
April 2021

Coffee consumption and risk of breast cancer: A Mendelian randomization study.

PLoS One 2021 19;16(1):e0236904. Epub 2021 Jan 19.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236904PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815134PMC
April 2021

Physical activity and all-cause and cause-specific mortality: assessing the impact of reverse causation and measurement error in two large prospective cohorts.

Eur J Epidemiol 2021 Mar 11;36(3):275-285. Epub 2021 Jan 11.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

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.
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http://dx.doi.org/10.1007/s10654-020-00707-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035269PMC
March 2021

Physical activity and the risk of abdominal aortic aneurysm: a systematic review and meta-analysis of prospective studies.

Sci Rep 2020 12 18;10(1):22287. Epub 2020 Dec 18.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, Paddington, London, W2 1PG, UK.

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, 409,732 participants) were included. The summary RR for high vs. low physical activity was 0.70 (95% CI: 0.56-0.87, I = 58%) and per 20 metabolic equivalent task (MET)-hours/week increase of activity was 0.84 (95% CI: 0.74-0.95, I = 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.
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http://dx.doi.org/10.1038/s41598-020-76306-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749100PMC
December 2020

Physical activity and the risk of heart failure: a systematic review and dose-response meta-analysis of prospective studies.

Eur J Epidemiol 2021 Apr 17;36(4):367-381. Epub 2020 Dec 17.

Department of Public Health and Nursing, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

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, I = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68-0.81, I = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59-0.74, I = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69-0.94, I = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86-0.95, I = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19-0.49, I = 96%, n = 6) for cardiorespiratory fitness. In dose-response analyses, the summary RRs were 0.89 (95% CI 0.83-0.95, I = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65-0.78, I = 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 activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure.
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http://dx.doi.org/10.1007/s10654-020-00693-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076120PMC
April 2021

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.

Clin Gastroenterol Hepatol 2020 Dec 29. Epub 2020 Dec 29.

CIBER Epidemiología y Salud Pública, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.

Background & Aims: Colorectal 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 and Nutrition cohort.

Methods: Scores 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 and Nutrition 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.

Results: Higher 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.

Conclusions: Metabolite 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.
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http://dx.doi.org/10.1016/j.cgh.2020.11.045DOI Listing
December 2020

Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Epidemiol 2021 03;50(1):212-222

Department of Public Health and Clinical Medicine, Section of Sustainable Health/Nutritional Research, Umeå University, Umeå, Sweden.

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.
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http://dx.doi.org/10.1093/ije/dyaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938513PMC
March 2021

Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies.

BMC Med 2020 11 20;18(1):360. Epub 2020 Nov 20.

Department of Epidemiology & Biostatistics, MRC Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W21PG, UK.

Background: Although 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.

Methods: We 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.

Results: A 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.

Conclusion: In 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.

Trial Registration: PROSPERO CRD42017069131 .
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http://dx.doi.org/10.1186/s12916-020-01817-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678319PMC
November 2020

Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Am J Clin Nutr 2020 Oct 6. Epub 2020 Oct 6.

Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.

Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking.

Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition).

Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis.

Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC.

Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
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http://dx.doi.org/10.1093/ajcn/nqaa277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779226PMC
October 2020

Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies.

Sci Rep 2020 09 29;10(1):16006. Epub 2020 Sep 29.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, Paddington, London, W2 1PG, UK.

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. 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. Thirteen cohort studies (10 publications) were included. The summary RR per 5 kg/m increase in body mass index (BMI) was 1.11 (95% CI 1.05-1.18, I = 50%), but the association was restricted to women (1.15, 95% CI 1.08-1.21, I = 17%) and not observed in men (0.89, 95% CI 0.73-1.09, I = 58%). The summary RR per 5 kg/m increment in BMI at age 18 years was 1.17 (95% CI 1.01-1.36, I = 26%, n = 3), and per 10 cm increase in waist circumference was 1.13 (95% CI 1.02-1.25, I = 44%, n = 2). 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.
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http://dx.doi.org/10.1038/s41598-020-71676-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524740PMC
September 2020

A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.

Sci Rep 2020 09 3;10(1):14541. Epub 2020 Sep 3.

Andalusian School of Public Health (EASP), Granada, Spain.

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/m) or obese (BMI ≥ 30 kg/m) 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.
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http://dx.doi.org/10.1038/s41598-020-71302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471961PMC
September 2020

Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses.

BMC Med 2020 09 3;18(1):229. Epub 2020 Sep 3.

Public Health Directorate, Asturias, Spain.

Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, 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, the 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 < 5 × 10) 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 (P = 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 suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P ≥ 0.2).

Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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http://dx.doi.org/10.1186/s12916-020-01703-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469292PMC
September 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 2020 11 31;43(11):2660-2667. Epub 2020 Aug 31.

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

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.
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http://dx.doi.org/10.2337/dc20-1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576430PMC
November 2020

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Sci Rep 2020 08 14;10(1):13814. Epub 2020 Aug 14.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80178, 3508 TD, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1038/s41598-020-70790-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429856PMC
August 2020

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

Sci Rep 2020 08 4;10(1):13151. Epub 2020 Aug 4.

Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research At Heinrich Heine University, Düsseldorf, Germany.

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.
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http://dx.doi.org/10.1038/s41598-020-70078-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403339PMC
August 2020

Association between sleep duration and mortality risk among adults with type 2 diabetes: a prospective cohort study.

Diabetologia 2020 11 16;63(11):2292-2304. Epub 2020 Jul 16.

Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

Aims/hypothesis: This study aimed to investigate whether the effects of sleep duration interacted with the presence of diabetes. We specifically sought to examine the relationship between sleep duration and all-cause and cause-specific mortality in people with type 2 diabetes across sex, age at diagnosis, duration of diabetes and treatment type.

Methods: The sample consisted of 273,029 adults, including 248,817 without diabetes and 24,212 with type 2 diabetes, who participated in the National Health Interview Survey from 2004 to 2013 and whose data were linked to a mortality database up to 31 December 2015. Sleep duration was measured using self-report, whereby participants were asked 'on average how long do you sleep each day (≤5, 6, 7, 8, 9 or ≥10 h/day)?' The relationship between sleep duration and mortality risk was investigated using Cox proportional hazards regression model, with adjustments for demographics, BMI, lifestyle behaviours and clinical variables.

Results: Absolute mortality rate was higher in adults with diabetes and extremes of sleep duration (≤5 h/day, 215.0 per 10,000 person-years; ≥10 h/day, 363.5 per 10,000 person-years). There was a non-significant interaction between sleep duration and the presence of diabetes (p for interaction = 0.08). A J-shaped relationship existed between sleep duration and all-cause mortality risk in people with type 2 diabetes. Compared with the reference group (7 h/day), both shorter and longer sleep durations were associated with increased risk of all-cause mortality (≤5 h/day, HR 1.24 [95% CI 1.09, 1.40]; 6 h/day, HR 1.13 [1.01, 1.28]; 8 h/day, HR 1.17 [1.06, 1.30]; ≥10 h/day, HR 1.83 [1.61, 2.08]). Similar associations were also observed for mortality risk from CVD, cancer, kidney disease, Alzheimer's disease and chronic lower respiratory diseases. Longer sleep duration in those with a younger age at diabetes onset was associated with greater risks of all-cause and CVD mortality. Shorter sleep duration in individuals treated with both insulin and oral glucose-lowering medication was also associated with higher risks of all-cause and CVD mortality.

Conclusions/interpretation: The associations between sleep duration and mortality risk may be different between diabetic and non-diabetic individuals. In people with type 2 diabetes, sleeping less or more than 7 h/day was associated with increased risk of all-cause and condition-specific mortality. The association was more prominent in those with a younger age at diabetes onset and receiving treatment with both oral glucose-lowering medication and insulin. This population may benefit from targeted sleep-related interventions to reduce the risks of adverse health outcomes. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05214-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527363PMC
November 2020

Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.

Adv Nutr 2020 11;11(6):1437-1452

Internal Medicine V, Department of Hematology & Oncology, Medical University Innsbruck, Innsbruck, Austria.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.
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http://dx.doi.org/10.1093/advances/nmaa077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666907PMC
November 2020
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