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  • 1. Jannasch, Franziska
    et al.
    Kroeger, Janine
    Agnoli, Claudia
    Barricarte, Aurelio
    Boeing, Heiner
    Cayssials, Valerie
    Colorado-Yohar, Sandra
    Dahm, Christina C.
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Freisling, Heinz
    Gunter, Marc J.
    Kerrison, Nicola D.
    Key, Timothy J.
    Khaw, Kay-Tee
    Kuehn, Tilman
    Kyro, Cecilie
    Mancini, Francesca Romana
    Mokoroa, Olatz
    Nilsson, Peter
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros Garcia, Jose Ramon
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Sahrai, Mohammad Sediq
    Schuebel, Ruth
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tong, Tammy Y. N.
    Tumino, Rosario
    Riboli, Elio
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita G.
    Schulze, Matthias B.
    Wareham, Nicholas J.
    Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations2019In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, no 6, p. 1047-1055Article in journal (Refereed)
    Abstract [en]

    Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence.

    Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries.

    Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association.

    Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea.

    Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

  • 2. Sasamoto, Naoko
    et al.
    Babic, Ana
    Rosner, Bernard A.
    Fortner, Renee T.
    Vitonis, Allison F.
    Yamamoto, Hidemi
    Fichorova, Raina N.
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Kvaskoff, Marina
    Fournier, Agnes
    Mancini, Francesca Romana
    Boeing, Heiner
    Trichopoulou, Antonia
    Peppa, Eleni
    Karakatsani, Anna
    Palli, Domenico
    Pala, Valeria
    Mattiello, Amalia
    Tumino, Rosario
    Grasso, Chiara C.
    Onland-Moret, N. Charlotte
    Weiderpass, Elisabete
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Rodriguez-Barranco, Miguel
    Colorado-Yohar, Sandra
    Barricarte, Aurelio
    Dorronsoro, Miren
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sartor, Hanna
    Khaw, Kay-Tee
    Key, Timothy J.
    Muller, David
    Riboli, Elio
    Gunter, Marc J.
    Dossus, Laure
    Kaaks, Rudolf
    Cramer, Daniel W.
    Tworoger, Shelley S.
    Terry, Kathryn L.
    Predicting Circulating CA125 Levels among Healthy Premenopausal Women2019In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 6, p. 1076-1085Article in journal (Refereed)
    Abstract [en]

    Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

  • 3. Ward, Heather A.
    et al.
    Murphy, Neil
    Weiderpass, Elisabete
    Leitzmann, Michael F.
    Aglago, Elom
    Gunter, Marc J.
    Freisling, Heinz
    Jenab, Mazda
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Carbonnel, Franck
    Kuehn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Merino, Susana
    Zamora-Ros, Raul
    Rodriguez-Barranco, Miguel
    Dorronsoro, Miren
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Perez-Cornago, Aurora
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Masala, Giovanna
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel
    Van Gils, Carla
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Rutegård, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Aune, Dagfinn
    Riboli, Elio
    Cross, Amanda J.
    Gallstones and incident colorectal cancer in a large pan-European cohort study2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 6, p. 1510-1516Article in journal (Refereed)
    Abstract [en]

    Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self‐reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow‐up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99–1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63–1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

  • 4. Ward, Heather A.
    et al.
    Whitman, Julia
    Muller, David C.
    Johansson, Mattias
    Jakszyn, Paula
    Weiderpass, Elisabete
    Palli, Domenico
    Fanidi, Anouar
    Vermeulen, Roel
    Tjonneland, Anne
    Hansen, Louise
    Dahm, Christina C.
    Overvad, Kim
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Affret, Aurelie
    Kaaks, Rudolf
    Fortner, Renee
    Boeing, Heiner
    Trichopoulou, Antonia
    La Vecchia, Carlo
    Kotanidou, Anastasia
    Berrino, Franco
    Krogh, Vittorio
    Tumino, Rosario
    Ricceri, Fulvio
    Panico, Salvatore
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H.
    Nost, Therese Haugdahl
    Sandanger, Torkjel M.
    Ramon Quiros, Jose
    Agudo, Antonio
    Rodriguez-Barranco, Miguel
    Larranaga, Nerea
    Maria Huerta, Jose
    Ardanaz, Eva
    Drake, Isabel
    Brunnstrom, Hans
    Johansson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Travis, Ruth C.
    Freisling, Heinz
    Stepien, Magdalena
    Merritt, Melissa A.
    Riboli, Elio
    Cross, Amanda J.
    Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2019In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 73, no 8, p. 1122-1132Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding.  

    Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available.

    Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset.

    Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk.

  • 5. Zamora-Ros, Raul
    et al.
    Cayssials, Valerie
    Franceschi, Silvia
    Kyrø, Cecilie
    Weiderpass, Elisabete
    Hennings, Joakim
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Truong, Thérèse
    Mancini, Francesca Romana
    Katzke, Verena
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Karakatsani, Anna
    Martimianaki, Georgia
    Palli, Domenico
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Lasheras, Cristina
    Rodríguez-Barranco, Miguel
    Amiano, Pilar
    Colorado-Yohar, Sandra M.
    Ardanaz, Eva
    Almquist, Martin
    Ericson, Ulrika
    Bueno-de-Mesquita, H. Bas
    Vermeulen, Roel
    Schmidt, Julie A.
    Byrnes, Graham
    Scalbert, Augustin
    Agudo, Antonio
    Rinaldi, Sabina
    Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed)
    Abstract [en]

    Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI >= 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.

  • 6. Zheng, Ju-Sheng
    et al.
    Imamura, Fumiaki
    Sharp, Stephen J.
    van der Schouw, Yvonne T.
    Sluijs, Ivonne
    Gundersen, Thomas E.
    Ardanaz, Eva
    Boeing, Heiner
    Bonet, Catalina
    Humberto Gomez, Jesus
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Jenab, Mazda
    Kuehn, 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
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sieri, Sabina
    Salamanca-Fernandez, Elena
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Butterworth, Adam S.
    Riboli, Elio
    Danesh, John
    Langenberg, Claudia
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 4, p. 1293-1303Article in journal (Refereed)
    Abstract [en]

    Background: 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: nonepimeric 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.

    Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography–mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.

    Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 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 nonepimeric 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], whereas 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)].

    Conclusions: Plasma nonepimeric 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.

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