Publications by authors named "Heinz Freisling"

145 Publications

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Nutrients 2021 Sep 8;13(9). Epub 2021 Sep 8.

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N-carboxy-methyllysine (CML), N-carboxyethyllysine (CEL), and N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HR. = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HR. = 0.92, 95% CI = 0.85-1.00), but not for CEL (HR. = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.
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http://dx.doi.org/10.3390/nu13093132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470201PMC
September 2021

Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study.

Clin Nutr 2021 09 21;40(9):5079-5088. Epub 2021 Aug 21.

Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity.

Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI).

Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline.

Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.
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http://dx.doi.org/10.1016/j.clnu.2021.08.009DOI Listing
September 2021

Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a cohort study of 2 524 926 Catalans.

J Clin Endocrinol Metab 2021 Jul 23. Epub 2021 Jul 23.

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.

Context: A comprehensive understanding of the association between body mass index (BMI) and COVID-19 is still lacking.

Objective: To investigate associations between BMI and risk of COVID-19 diagnosis, hospitalisation with COVID-19, and death after a COVID-19 diagnosis or hospitalisation (subsequent death), accounting for potential effect modification by age and sex.

Design: Population-based cohort study.

Setting: Primary care records covering >80% of the Catalan population, linked to region-wide testing, hospital, and mortality records from March to May 2020.

Participants: Adults (≥18 years) with at least one measurement of weight and height.

Main Outcome Measures: Hazard ratios (HR) for each outcome.

Results: We included 2 524 926 participants. After 67 days of follow-up, 57 443 individuals were diagnosed with COVID-19, 10 862 were hospitalised with COVID-19, and 2467 had a subsequent death. BMI was positively associated with being diagnosed and hospitalised with COVID-19. Compared to a BMI of 22kg/m 2, the HR (95%CI) of a BMI of 31kg/m 2 was 1.22 (1.19-1.24) for diagnosis, and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalisation without and with a prior outpatient diagnosis, respectively. The association between BMI and subsequent death was J-shaped, with a modestly higher risk of death among individuals with BMIs ≤19kg/m 2 and a more pronounced increasing risk for BMIs ≥40kg/m 2. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients.

Conclusions: There is a monotonic association between BMI and COVID-19 diagnosis and hospitalisation risks, but a J-shaped one with mortality. More research is needed to unravel the mechanisms underlying these relationships.
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http://dx.doi.org/10.1210/clinem/dgab546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344917PMC
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

Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank.

Cancers (Basel) 2021 Jun 1;13(11). Epub 2021 Jun 1.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, CEDEX 08, 69372 Lyon, France.

We investigated associations between serum levels of bilirubin, an endogenous antioxidant, and gastrointestinal cancer risk. In the UK Biobank, prediagnostic serum levels of total bilirubin were measured in blood samples collected from 440,948 participants. In multivariable-adjusted Cox proportional hazard regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between bilirubin levels and gastrointestinal cancer risk (colorectum, esophagus, stomach, mouth, pancreas, and liver). After a median follow-up of 7.1 years (interquartile range: 1.4), 5033 incident gastrointestinal cancer cases were recorded. In multivariable-adjusted models, bilirubin levels were negatively associated with risk of esophageal adenocarcinoma (EAC, HR per 1-SD increment in log-total bilirubin levels 0.72, 95%CI 0.56-0.92, = 0.01). Weak and less robust negative associations were observed for colorectal cancer (CRC, HR per 1-SD increment in log-total bilirubin levels 0.95, 95%CI 0.88-1.02, = 0.14). Bilirubin levels were positively associated with risk of hepatocellular carcinoma (HCC, HR per 1-SD increment in log-total bilirubin levels 2.07, 95%CI 1.15-3.73, = 0.02) and intrahepatic bile duct (IBD) cancer (HR per 1-SD increment 1.67, 95%CI 1.07-2.62, = 0.03). We found no associations with risks of stomach, oral, and pancreatic cancers. Prediagnostic serum levels of bilirubin were negatively associated with risk of EAC and positively associated with HCC and IBD cancer. Further studies are warranted to replicate our findings for specific GI cancers.
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http://dx.doi.org/10.3390/cancers13112749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198711PMC
June 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

Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort.

Gut Microbes 2021 Jan-Dec;13(1):1-14

Department of Medical Biosciences, Pathology, Umeå University, Ireland.

Experimental evidence has implicated genotoxic () and enterotoxigenic (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to and ETBF with CRC.The IgA-positivity of any of the tested antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (= 0.095). Sero-positivity to and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.
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http://dx.doi.org/10.1080/19490976.2021.1903825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078709PMC
April 2021

Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study.

Carcinogenesis 2021 05;42(5):705-713

Office of the Director, International Agency for Research on Cancer (IARC), Lyon, France.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs-Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)-were measured by ultra-performance liquid chromatography-tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.
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http://dx.doi.org/10.1093/carcin/bgab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162627PMC
May 2021

Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium.

Br J Cancer 2021 May 26;124(11):1882-1890. Epub 2021 Mar 26.

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

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.

Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.

Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.

Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.
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http://dx.doi.org/10.1038/s41416-021-01347-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144608PMC
May 2021

Genetically Raised Circulating Bilirubin Levels and Risk of Ten Cancers: A Mendelian Randomization Study.

Cells 2021 02 15;10(2). Epub 2021 Feb 15.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 69008 Lyon, France.

Bilirubin, an endogenous antioxidant, may play a protective role in cancer development. We applied two-sample Mendelian randomization to investigate whether genetically raised bilirubin levels are causally associated with the risk of ten cancers (pancreas, kidney, endometrium, ovary, breast, prostate, lung, Hodgkin's lymphoma, melanoma, and neuroblastoma). The number of cases and their matched controls of European descent ranged from 122,977 and 105,974 for breast cancer to 1200 and 6417 for Hodgkin's lymphoma, respectively. A total of 115 single-nucleotide polymorphisms (SNPs) associated ( < 5 × 10) with circulating total bilirubin, extracted from a genome-wide association study in the UK Biobank, were used as instrumental variables. One SNP (rs6431625) in the promoter region of the uridine-diphosphoglucuronate glucuronosyltransferase1A1 ( gene explained 16.9% and the remaining 114 SNPs (non- SNPs) explained 3.1% of phenotypic variance in circulating bilirubin levels. A one-standarddeviation increment in circulating bilirubin (≈ 4.4 µmol/L), predicted by non- SNPs, was inversely associated with risk of squamous cell lung cancer and Hodgkin's lymphoma (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.73-0.99, 0.04 and OR 0.64, 95% CI 0.42-0.99, 0.04, respectively), which was confirmed after removing potential pleiotropic SNPs. In contrast, a positive association was observed with the risk of breast cancer after removing potential pleiotropic SNPs (OR 1.12, 95% CI 1.04-1.20, 0.002). There was little evidence for robust associations with the other seven cancers investigated. Genetically raised bilirubin levels were inversely associated with risk of squamous cell lung cancer as well as Hodgkin's lymphoma and positively associated with risk of breast cancer. Further studies are required to investigate the utility of bilirubin as a low-cost clinical marker to improve risk prediction for certain cancers.
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http://dx.doi.org/10.3390/cells10020394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918902PMC
February 2021

Taxonomic Composition and Diversity of the Gut Microbiota in Relation to Habitual Dietary Intake in Korean Adults.

Nutrients 2021 Jan 26;13(2). Epub 2021 Jan 26.

Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), 69008 Lyon, France.

We investigated associations of habitual dietary intake with the taxonomic composition and diversity of the human gut microbiota in 222 Koreans aged 18-58 years in a cross-sectional study. Gut microbiota data were obtained by 16S rRNA gene sequencing on DNA extracted from fecal samples. The habitual diet for the previous year was assessed by a food frequency questionnaire. After multivariable adjustment, intake of several food groups including vegetables, fermented legumes, legumes, dairy products, processed meat, and non-alcoholic beverages were associated with major phyla of the gut microbiota. A dietary pattern related to higher α-diversity (HiαDP) derived by reduced rank regression was characterized by higher intakes of fermented legumes, vegetables, seaweeds, and nuts/seeds and lower intakes of non-alcoholic beverages. The HiαDP was positively associated with several genera of such as , , and (all < 0.05). Among enterotypes identified by principal coordinate analysis based on the β-diversity, the enterotype had higher HiαDP scores and was strongly positively associated with intakes of vegetables, seaweeds, and nuts/seeds, compared to the two other enterotypes. We conclude that a plant- and fermented food-based diet was positively associated with some genera of (e.g., , , and ) reflecting better gut microbial health.
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http://dx.doi.org/10.3390/nu13020366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912254PMC
January 2021

Body mass index and waist circumference in relation to the risk of 26 types of cancer: a prospective cohort study of 3.5 million adults in Spain.

BMC Med 2021 01 14;19(1):10. Epub 2021 Jan 14.

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Gran Via Corts Catalanes, 587 àtic, 08007, Barcelona, Spain.

Background: A high body mass index (BMI) has been associated with increased risk of several cancers; however, whether BMI is related to a larger number of cancers than currently recognized is unclear. Moreover, whether waist circumference (WC) is more strongly associated with specific cancers than BMI is not well established. We aimed to investigate the associations between BMI and 26 cancers accounting for non-linearity and residual confounding by smoking status as well as to compare cancer risk estimates between BMI and WC.

Methods: Prospective cohort study with population-based electronic health records from Catalonia, Spain. We included 3,658,417 adults aged ≥ 18 years and free of cancer at baseline between 2006 and 2017. Our main outcome measures were cause-specific hazard ratios (HRs) with 99% confidence intervals (CIs) for incident cancer at 26 anatomical sites.

Results: After a median follow-up time of 8.3 years, 202,837 participants were diagnosed with cancer. A higher BMI was positively associated with risk of nine cancers (corpus uteri, kidney, gallbladder, thyroid, colorectal, breast post-menopausal, multiple myeloma, leukemia, non-Hodgkin lymphoma) and was positively associated with three additional cancers among never smokers (head and neck, brain and central nervous system, Hodgkin lymphoma). The respective HRs (per 5 kg/m increment) ranged from 1.04 (99%CI 1.01 to 1.08) for non-Hodgkin lymphoma to 1.49 (1.45 to 1.53) for corpus uteri cancer. While BMI was negatively associated to five cancer types in the linear analyses of the overall population, accounting for non-linearity revealed that BMI was associated to prostate cancer in a U-shaped manner and to head and neck, esophagus, larynx, and trachea, bronchus and lung cancers in an L-shaped fashion, suggesting that low BMIs are an approximation of heavy smoking. Of the 291,305 participants with a WC measurement, 27,837 were diagnosed with cancer. The 99%CIs of the BMI and WC point estimates (per 1 standard deviation increment) overlapped for all cancers.

Conclusions: In this large Southern European study, a higher BMI was associated with increased risk of twelve cancers, including four hematological and head and neck (only among never smokers) cancers. Furthermore, BMI and WC showed comparable estimates of cancer risk associated with adiposity.
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http://dx.doi.org/10.1186/s12916-020-01877-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807518PMC
January 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

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

Int J Cancer 2021 05 12;148(9):2115-2128. Epub 2020 Nov 12.

Department of Oncology, Lund University, Lund, Sweden.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
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http://dx.doi.org/10.1002/ijc.33369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048490PMC
May 2021

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort.

Cancer Epidemiol Biomarkers Prev 2021 01 20;30(1):182-192. Epub 2020 Oct 20.

Public Health Directorate, Oviedo, Spain.

Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.

Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.

Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (OR, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (OR, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (OR, 1.00; 95% CI, 0.68-1.48; for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).

Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.

Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0855DOI Listing
January 2021

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Int J Cancer 2021 04 9;148(7):1637-1651. Epub 2020 Nov 9.

Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
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http://dx.doi.org/10.1002/ijc.33339DOI Listing
April 2021

Gilbert's syndrome, circulating bilirubin and lung cancer: a genetic advantage?

Thorax 2020 11 6;75(11):916-917. Epub 2020 Oct 6.

Faculty of Life Sciences, Department of Nutritional Sciences, University of Vienna, Wien, Austria.

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http://dx.doi.org/10.1136/thoraxjnl-2020-215642DOI Listing
November 2020

The Association between Serum Bilirubin Levels and Colorectal Cancer Risk: Results from the Prospective Cooperative Health Research in the Region of Augsburg (KORA) Study in Germany.

Antioxidants (Basel) 2020 Sep 24;9(10). Epub 2020 Sep 24.

Department of Nutritional Sciences, Faculty of Life Sciences, University of Vienna, 1010 Vienna, Austria.

Emerging studies have suggested that bilirubin, particularly unconjugated bilirubin (UCB), has substantial anti-inflammatory and antioxidant properties that protect against oxidative stress-associated diseases such as cancer. Few observational studies have investigated the etiological role of bilirubin in colorectal cancer (CRC) development. In this case-control study, nested in the population-based prospective cohort of the Cooperative Health Research in the Region of Augsburg (KORA) study in south Germany, pre-diagnostic circulating UCB concentrations were measured by high-performance liquid chromatography in 77 CRC cases and their individually matched controls. Multivariable unconditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for associations between log-transformed UCB levels (log-UCB), standardized per one-standard-deviation (one-SD) increment, and CRC risk. The models were a priori stratified by sex based on previous evidence. In the fully adjusted models, each one-SD increment in log-UCB was indicative of a positive association with CRC risk (OR, 1.20; 95% CI, 0.52-2.79) among men, and of an inverse association (OR, 0.76; 95% CI, 0.34-1.84) among women (P = 0.4 for differences between men and women). We found little evidence for sex-specific associations of circulating bilirubin with CRC risk, and further studies are needed to confirm or refute the potential associations.
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http://dx.doi.org/10.3390/antiox9100908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598693PMC
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

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study.

Am J Clin Nutr 2020 09;112(3):631-643

Center for Research in Epidemiology and Population Health, University Paris-South, Faculty of Medicine, University Versailles-St Quentin, National Institute for Health and Medical Research, Université Paris-Saclay, Villejuif, France.

Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk.

Objectives: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes.

Methods: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models.

Results: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d].

Conclusions: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.
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http://dx.doi.org/10.1093/ajcn/nqaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458777PMC
September 2020

Diet and sedentary behaviour in relation to mortality in US adults with a cardiovascular condition: results from the National Health and Nutrition Examination Survey linked to the US mortality registry.

Br J Nutr 2020 12 30;124(12):1329-1337. Epub 2020 Jun 30.

Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.

CVD is the most common chronic condition and the highest cause of mortality in the USA. The aim of the present work was to investigate diet and sedentary behaviour in relation to mortality in US CVD survivors. The National Health and Nutrition Examination Surveys conducted between 1999 and 2014 linked to the US mortality registry updated to 2015 were investigated. Multivariate adjusted Cox regression was used to derive mortality hazards in relation to sedentary behaviour and nutrient intake. A multiplicative and additive interaction analysis was conducted to evaluate how sedentariness and diet influence mortality in US CVD survivors. A sample of 2473 participants followed for a median period of 5·6 years resulted in 761 deaths, and 199 deaths were due to CVD. A monotone increasing relationship between time spent in sedentary activities and mortality risk was observed for all-cause and CVD mortality (hazard ratio (HR) = 1·20, 95 % CI 1·09, 1·31 and HR = 1·19, 95 % CI 1·00, 1·67, respectively). Inverse mortality risks in the range of 22-34 % were observed when comparing the highest with the lowest tertile of dietary fibre, vitamin A, carotene, riboflavin and vitamin C. Sedentariness below 360 min/d and dietary fibre and vitamin intake above the median interact on an additive scale influencing positively all-cause and CVD mortality risk. Reduced sedentariness in combination with a varied diet rich in dietary fibre and vitamins appears to be a useful strategy to reduce all-cause and CVD mortality in US CVD survivors.
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http://dx.doi.org/10.1017/S0007114520002391DOI Listing
December 2020

Metabolic tracking of isoflavones in soybean products and biosamples from healthy adults after fermented soybean consumption.

Food Chem 2020 Nov 11;330:127317. Epub 2020 Jun 11.

Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, South Korea. Electronic address:

Fermentation may enhance the nutritional properties of foods by increasing metabolite bioactivity or bioavailability. This study explored the effect of fermentation on isoflavone bioavailability and metabolism. Isoflavone metabolites were tracked in foods and biospecimens of healthy adults after fermented soybean (FS) or non-fermented soybean (NFS) consumption in a randomized, controlled, crossover intervention study. The change in soybean isoflavones caused by fermentation resulted in faster absorption and higher bioavailability after consumption of FS. Although the urinary level of total isoflavone metabolites was similar after the consumption of the two diets, urinary genistein 7-O-sulfate was derived as a discriminant metabolite for the FS diet by partial least squares discriminant analysis. This study suggests that an isoflavone conjugate profile might be a more appropriate marker than total isoflavone levels for discriminating between the consumption of FS and NFS diets.
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http://dx.doi.org/10.1016/j.foodchem.2020.127317DOI Listing
November 2020

Intentional Weight Loss and Cancer Risk: Never Too Late to Lose Weight.

JNCI Cancer Spectr 2019 Dec 13;3(4):pkz059. Epub 2019 Sep 13.

Section of Nutrition and Metabolism, International Agency for Research on Cancer/World Health Organization (IARC/WHO), Lyon, France.

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http://dx.doi.org/10.1093/jncics/pkz059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050009PMC
December 2019

Diet and sedentary behaviour in relation to cancer survival. A report from the national health and nutrition examination survey linked to the U.S. mortality registry.

Clin Nutr 2020 11 18;39(11):3489-3496. Epub 2020 Mar 18.

Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa.

Background & Aims: Cancer is the second most common chronic disease and cause of death in the United States. Our aim was to evaluate the associations of sedentary behavior and nutrient intakes with total and cancer-specific mortality among US cancer survivors.

Methods: Data from 2371 cancer survivors collected by the US National Health and Nutrition Examination Survey between 1999 and 2014 were linked to the US mortality registry. Multivariable adjusted Cox proportional hazard models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cancer-specific mortality associated with sedentary time and nutrient intakes. The interaction between time spent on sedentary activities and nutrient intake was evaluated on additive and multiplicative scales.

Results: During a median observational period of 5.7 years, 532 total deaths occurred among cancer survivors, of which 180 were cancer-specific. A monotonic increasing linear relationship between time spent sitting and all-cause mortality was observed (HR = 1.15, 95% CI = 1.03, 1.28 per one standard deviation increment). The highest versus the lowest tertiles of intakes of dietary fiber, carotene, niacin, thiamine, riboflavin, vitamin B6, vitamin B12, and vitamin C were inversely associated with all-cause and cancer-specific mortality (HRs = 0.48 to 0.75). The inverse associations with all-cause mortality were more pronounced for combinations of low sedentary behaviour and high intakes of dietary fiber, carotenoids, vitamin B12, and vitamin C.

Conclusion: Our findings support recommendations for cancer survivors to reduce time spent sedentary and to follow a balanced diet with adequate intakes of dietary fiber and micronutrients.
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http://dx.doi.org/10.1016/j.clnu.2020.03.013DOI Listing
November 2020

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

Breast Cancer Res 2020 01 13;22(1). Epub 2020 Jan 13.

Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.

Background: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.

Methods: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).

Results: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.

Conclusions: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
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http://dx.doi.org/10.1186/s13058-019-1244-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958698PMC
January 2020

Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

BMC Med 2020 01 10;18(1). Epub 2020 Jan 10.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.

Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs.

Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles.

Conclusion: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
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http://dx.doi.org/10.1186/s12916-019-1474-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953215PMC
January 2020

Cumulative exposure to premenopausal obesity and risk of postmenopausal cancer: A population-based study in Icelandic women.

Int J Cancer 2020 08 24;147(3):793-802. Epub 2019 Dec 24.

Section of Cancer Surveillance, International Agency for Research on Cancer (IARC-WHO), Lyon, France.

Obesity, often assessed at one point in time, is an established risk factor of several types of cancer, however, associations with cumulative exposure to obesity across the life course are not well understood. We investigated the relationship between combined measures of duration and intensity of premenopausal overweight and obesity and the incidence of postmenopausal breast, endometrial, and colorectal cancers in Icelandic women. Body mass index (BMI) trajectories between ages 20 and 50 of 88,809 women from the Cancer Detection Clinic Cohort were predicted using growth curve models. Indicators of overweight and obesity duration and intensity were computed and their association with risk of postmenopausal breast, endometrial, and colorectal cancers was examined using multivariate Cox models for subjects followed-up beyond the age of 50 (n = 67,488). During a mean follow-up of 17 years, incident events of 3,016 postmenopausal breast, 410 endometrial and 987 colorectal cancers were ascertained. Each 0.1 kg/m per year increase in BMI between ages 20 and 50 was positively associated with risks of postmenopausal breast, endometrium and colorectal cancers with hazard ratios equal to 1.09 (95% Confidence Interval (CI):1.04-1.13), 1.31 (95% CI: 1.18-1.44) and 1.10 (95% CI: 1.00-1.21), respectively. Compared to women who were never obese, cumulative BMI × years of obesity were linearly positively associated with risk of endometrial cancer, whereas the association with breast cancer was initially positive, but leveled off with increasing cumulative BMI × years. Cumulative exposure to obesity may provide additional insights into the etiology of cancer and should be considered in future studies that assess obesity-cancer relationships.
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http://dx.doi.org/10.1002/ijc.32805DOI Listing
August 2020
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