• Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study.

      Zheng, Ju-Sheng; Sharp, Stephen J; Imamura, Fumiaki; Koulman, Albert; Schulze, Matthias B; Ye, Zheng; Griffin, Jules; Guevara, Marcela; Huerta, José María; Kröger, Janine; Sluijs, Ivonne; Agudo, Antonio; Barricarte, Aurelio; Boeing, Heiner; Colorado-Yohar, Sandra; Dow, Courtney; Dorronsoro, Miren; Dinesen, Pia T; Fagherazzi, Guy; Franks, Paul W; Feskens, Edith J M; Kühn, Tilman; Katzke, Verena Andrea; Key, Timothy J; Khaw, Kay-Tee; de Magistris, Maria Santucci; Mancini, Francesca Romana; Molina-Portillo, Elena; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, Jose Ramón; Rolandsson, Olov; Ricceri, Fulvio; Spijkerman, Annemieke M W; Slimani, Nadia; Tagliabue, Giovanna; Tjonneland, Anne; Tumino, Rosario; van der Schouw, Yvonne T; Langenberg, Claudia; Riboli, Elio; Forouhi, Nita G; Wareham, Nicholas J (2017-11-17)
      Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways.
    • Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study.

      Zheng, Ju-Sheng; Imamura, Fumiaki; Sharp, Stephen J; van der Schouw, Yvonne T; Sluijs, Ivonne; Gundersen, Thomas E; Ardanaz, Eva; Boeing, Heiner; Bonet, Catalina; Gómez, Jesus Humberto; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W; Jenab, Mazda; Kühn, Tilman; Kaaks, Rudolf; Key, Timothy J; Khaw, Kay-Tee; Lasheras, Cristina; Mokoroa, Olatz; Mancini, Francesca Romana; Nilsson, Peter M; Overvad, Kim; Panico, Salvatore; Palli, Domenico; Rolandsson, Olov; Sieri, Sabina; Salamanca-Fernández, Elena; Sacerdote, Carlotta; Spijkerman, Annemieke Mw; Stepien, Magdalena; Tjonneland, Anne; Tumino, Rosario; Butterworth, Adam S; Riboli, Elio; Danesh, John; Langenberg, Claudia; Forouhi, Nita G; Wareham, Nicholas J (2018-11-09)
      Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: non-epimeric and epimeric 25(OH)D3 stereoisomers; and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D. This analysis in the EPIC-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13562 subcohort members. Plasma vitamin D metabolites were quantified by liquid-chromatography mass-spectrometry. We used multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates combined across countries using random-effects meta-analysis. The mean concentrations (standard deviation) of total 25(OH)D, non-epimeric 25(OH)D3, epimeric 25(OH)D3 and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and non-epimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1-SD=0.81 (95%CI: 0.77, 0.86) for both variables], while epimeric 25(OH)D3 was positively associated: per 1-SD HR=1.16 (1.09, 1.25). There was no statistically significant association with T2D for 25(OH)D2 [per 1-SD HR=0.94 (0.76, 1.18)]. Plasma non-epimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.
    • Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.

      Kröger, Janine; Meidtner, Karina; Stefan, Norbert; Guevara, Marcela; Kerrison, Nicola D; Ardanaz, Eva; Aune, Dagfinn; Boeing, Heiner; Dorronsoro, Miren; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W; Freisling, Heinz; Gunter, Marc J; Huerta, José María; Kaaks, Rudolf; Key, Timothy J; Khaw, Kay Tee; Krogh, Vittorio; Kühn, Tilman; Mancini, Francesca Romana; Mattiello, Amalia; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Salamanca-Fernández, Elena; Sluijs, Ivonne; Spijkerman, Annemieke Mw; Tjonneland, Anne; Tsilidis, Konstantinos K; Tumino, Rosario; van der Schouw, Yvonne T; Forouhi, Nita G; Sharp, Stephen J; Langenberg, Claudia; Riboli, Elio; Schulze, Matthias B; Wareham, Nicholas J (2018-03-09)
      Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian Randomization study with SNPs located in the fetuin-A-encodingAHSGgene. We used data from eight European countries of the prospective EPIC-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 cases. A genetic score of theAHSGSNPs was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/ml higher fetuin-A concentration with diabetes risk (HR 1.02 [95%-CI 0.97, 1.07]). Combining our results with those from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 cases) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistical evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study doesn't support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
    • Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

      Gunter, Marc J; Murphy, Neil; Cross, Amanda J; Dossus, Laure; Dartois, Laureen; Fagherazzi, Guy; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Aleksandrova, Krasimira; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Larsen, Sofus Christian; Redondo Cornejo, Maria Luisa; Agudo, Antonio; Sánchez Pérez, María José; Altzibar, Jone M; Navarro, Carmen; Ardanaz, Eva; Khaw, Kay-Tee; Butterworth, Adam; Bradbury, Kathryn E; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Vineis, Paolo; Panico, Salvatore; Tumino, Rosario; Bueno-de-Mesquita, Bas; Siersema, Peter; Leenders, Max; Beulens, Joline W J; Uiterwaal, Cuno U; Wallström, Peter; Nilsson, Lena Maria; Landberg, Rikard; Weiderpass, Elisabete; Skeie, Guri; Braaten, Tonje; Brennan, Paul; Licaj, Idlir; Muller, David C; Sinha, Rashmi; Wareham, Nick; Riboli, Elio (2017-08-15)
      The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.
    • A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study.

      Imamura, Fumiaki; Sharp, Stephen J; Koulman, Albert; Schulze, Matthias B; Kröger, Janine; Griffin, Julian L; Huerta, José M; Guevara, Marcela; Sluijs, Ivonne; Agudo, Antonio; Ardanaz, Eva; Balkau, Beverley; Boeing, Heiner; Chajes, Veronique; Dahm, Christina C; Dow, Courtney; Fagherazzi, Guy; Feskens, Edith J M; Franks, Paul W; Gavrila, Diana; Gunter, Marc; Kaaks, Rudolf; Key, Timothy J; Khaw, Kay-Tee; Kühn, Tilman; Melander, Olle; Molina-Portillo, Elena; Nilsson, Peter M; Olsen, Anja; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Rolandsson, Olov; Sieri, Sabina; Sacerdote, Carlotta; Slimani, Nadia; Spijkerman, Annemieke M W; Tjønneland, Anne; Tumino, Rosario; van der Schouw, Yvonne T; Langenberg, Claudia; Riboli, Elio; Forouhi, Nita G; Wareham, Nick J (2017-10)
      Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.
    • Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies.

      Smith, Todd; Muller, David C; Moons, Karel G M; Cross, Amanda J; Johansson, Mattias; Ferrari, Pietro; Fagherazzi, Guy; Peeters, Petra H M; Severi, Gianluca; Hüsing, Anika; Kaaks, Rudolf; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Bonet, Catalina; Rodriguez-Barranco, Miguel; Huerta, Jose Maria; Barricarte Gurrea, Aurelio; Bradbury, Kathryn E; Trichopoulou, Antonia; Bamia, Christina; Orfanos, Philippos; Palli, Domenico; Pala, Valeria; Vineis, Paolo; Bueno-de-Mesquita, Bas; Ohlsson, Bodil; Harlid, Sophia; Van Guelpen, Bethany; Skeie, Guri; Weiderpass, Elisabete; Jenab, Mazda; Murphy, Neil; Riboli, Elio; Gunter, Marc J; Aleksandrova, Krasimira Jekova; Tzoulaki, Ioanna (2018-04-03)
      To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.
    • Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study.

      Vissers, Linda E T; Sluijs, Ivonne; van der Schouw, Yvonne T; Forouhi, Nita G; Imamura, Fumiaki; Burgess, Stephen; Barricarte, Aurelio; Boeing, Heiner; Bonet, Catalina; Chirlaque, Maria-Dolores; Fagherazzi, Guy; Franks, Paul W; Freisling, Heinz; Gunter, Marc J; Quirós, J Ramón; Ibsen, Daniel B; Kaaks, Rudolf; Key, Timothy; Khaw, Kay T; Kühn, Tilman; Mokoroa, Olatz; Nilsson, Peter M; Overvad, Kim; Pala, Valeria; Palli, Domenico; Panico, Salvatore; Sacerdote, Carlotta; Spijkerman, Annemieke M W; Tjonneland, Anne; Tumino, Rosario; Rodríguez-Barranco, Miguel; Rolandsson, Olov; Riboli, Elio; Sharp, Stephen J; Langenberg, Claudia; Wareham, Nicholas J (2019-02-06)
      To estimate the causal association between intake of dairy products and incident type 2 diabetes. The analysis included 21,820 European individuals (9,686 diabetes cases) of the EPIC-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a SNP for lactase persistence (LP) which enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression. Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratio 0.99 rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations we consider it unlikely that this has caused the observed null result.
    • Inflammatory potential of the diet and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

      Agudo, Antonio; Cayssials, Valerie; Bonet, Catalina; Tjønneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Affret, Aurélie; Fagherazzi, Guy; Katzke, Verena; Schübel, Ruth; Trichopoulou, Antonia; Karakatsani, Anna; La Vecchia, Carlo; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvatore; Bueno-de-Mesquita, Bas; Peeters, Petra H; Weiderpass, Elisabete; Skeie, Guri; Nøst, Theresa H; Lasheras, Cristina; Rodríguez-Barranco, Miguel; Amiano, Pilar; Chirlaque, María-Dolores; Ardanaz, Eva; Ohlsson, Bodil; Dias, Joana A; Nilsson, Lena M; Myte, Robin; Khaw, Kay-Tee; Perez-Cornago, Aurora; Gunter, Marc; Huybrechts, Inge; Cross, Amanda J; Tsilidis, Kostas; Riboli, Elio; Jakszyn, Paula (2018-04-01)
      Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation.
    • Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes: systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct.

      Li, Sherly X; Imamura, Fumiaki; Ye, Zheng; Schulze, Matthias B; Zheng, Jusheng; Ardanaz, Eva; Arriola, Larraitz; Boeing, Heiner; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W; Agudo, Antonio; Grioni, Sara; Kaaks, Rudolf; Katzke, Verena A; Key, Timothy J; Khaw, Kay Tee; Mancini, Francesca R; Navarro, Carmen; Nilsson, Peter M; Onland-Moret, N Charlotte; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sánchez, María-José; Slimani, Nadia; Sluijs, Ivonne; Spijkerman, Annemieke Mw; Tjonneland, Anne; Tumino, Rosario; Sharp, Stephen J; Riboli, Elio; Langenberg, Claudia; Scott, Robert A; Forouhi, Nita G; Wareham, Nicholas J (2017-07)
      Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.Objective: We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.Design: We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.Results: Thirteen observational studies met the eligibility criteria (n < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.
    • Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

      Li, Sherly X; Imamura, Fumiaki; Schulze, Matthias B; Zheng, Jusheng; Ye, Zheng; Agudo, Antonio; Ardanaz, Eva; Aune, Dagfinn; Boeing, Heiner; Dorronsoro, Miren; Dow, Courtney; Fagherazzi, Guy; Grioni, Sara; Gunter, Marc J; Huerta, José María; Ibsen, Daniel B; Jakobsen, Marianne Uhre; Kaaks, Rudolf; Key, Timothy J; Khaw, Kay-Tee; Kyrø, Cecilie; Mancini, Francesca Romana; Molina-Portillo, Elena; Murphy, Neil; Nilsson, Peter M; Onland-Moret, N Charlotte; Palli, Domenico; Panico, Salvatore; Poveda, Alaitz; Quirós, J Ramón; Ricceri, Fulvio; Sluijs, Ivonne; Spijkerman, Annemieke M W; Tjonneland, Anne; Tumino, Rosario; Winkvist, Anna; Langenberg, Claudia; Sharp, Stephen J; Riboli, Elio; Scott, Robert A; Forouhi, Nita G; Wareham, Nicholas J (2018-03-17)
      Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.
    • Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition.

      Ward, Heather A; Wark, Petra A; Muller, David C; Steffen, Annika; Johansson, Mattias; Norat, Teresa; Gunter, Marc J; Overvad, Kim; Dahm, Christina C; Halkjær, Jytte; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Mesrine, Sylvie; Brennan, Paul; Freisling, Heinz; Li, Kuanrong; Kaaks, Rudolf; Trichopoulou, Antonia; Lagiou, Pagona; Panico, Salavatore; Grioni, Sara; Tumino, Rosario; Vineis, Paolo; Palli, Domenico; Peeters, Petra H M; Bueno-de-Mesquita, H Bas; Weiderpass, Elisabete; Agudo, Antonio; Quirós, Jose Ramón; Larrañaga, Nerea; Ardanaz, Eva; Huerta, José María; Sánchez, María-José; Laurell, Göran; Johansson, Ingegerd; Westin, Ulla; Wallström, Peter; Bradbury, Kathryn E; Wareham, Nicholas J; Khaw, Kay-Tee; Pearson, Clare; Boeing, Heiner; Riboli, Elio (2017-06)
      Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error.Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: <22.5 kg/m2, normal weight (reference): 22.5-24.9 kg/m2, overweight 25-29.9 kg/m2, obese: ≥30 kg/m2], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models.Results: Among men, a BMI < 22.5 kg/m2 was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23-2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02-1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38-1.93). After stratification by smoking status, the association for WHR was present only among smokers (Pinteraction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07-1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21-1.65).Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated.Impact: Strategies to reduce obesity may beneficially impact head and neck cancer incidence. Cancer Epidemiol Biomarkers Prev; 26(6); 895-904. ©2017 AACR.
    • Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study.

      Freisling, Heinz; Noh, Hwayoung; Slimani, Nadia; Chajès, Véronique; May, Anne M; Peeters, Petra H; Weiderpass, Elisabete; Cross, Amanda J; Skeie, Guri; Jenab, Mazda; Mancini, Francesca R; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Katzke, Verena A; Kühn, Tilman; Steffen, Annika; Boeing, Heiner; Tjønneland, Anne; Kyrø, Cecilie; Hansen, Camilla P; Overvad, Kim; Duell, Eric J; Redondo-Sánchez, Daniel; Amiano, Pilar; Navarro, Carmen; Barricarte, Aurelio; Perez-Cornago, Aurora; Tsilidis, Konstantinos K; Aune, Dagfinn; Ward, Heather; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Berrino, Franco; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Ericson, Ulrika; Sonestedt, Emily; Winkvist, Anna; Braaten, Tonje; Romieu, Isabelle; Sabaté, Joan (2017-07-21)
      There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years.