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  • 1. Butt, Julia
    et al.
    Jenab, Mazda
    Pawlita, Michael
    Overvad, Kim
    Tjonneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Mancini, Francesca Romana
    Kaaks, Rudolf
    Kühn, Tilman
    Boeing, Heiner
    Trichopoulou, Antonia
    Karakatsani, Anna
    Palli, Domenico
    Pala, Valeria Maria
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    van Gils, Carla H.
    Vermeulen, Roel C. H.
    Weiderpass, Elisabete
    Quiros, Jose Ramon
    Duell, Eric Jeffrey
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Maria Huerta, Jose
    Ardanaz, Eva
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Perez-Cornago, Aurora
    Gunter, Marc J.
    Murphy, Neil
    Freisling, Heinz
    Aune, Dagfinn
    Waterboer, Tim
    Hughes, David J.
    Antibody Responses to Fusobacterium nucleatum Proteins in Prediagnostic Blood Samples are not Associated with Risk of Developing Colorectal Cancer2019Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 9, s. 1552-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is a lack of prospective data on the potential association of Fusobacterium nucleatum (F. nucleatum) and colorectal cancer risk. In this study, we assessed whether antibody responses to F. nucleatum are associated with colorectal cancer risk in prediagnostic serum samples in the European Prospective Investigation into Nutrition and Cancer (EPIC) cohort.

    Methods: We applied a multiplex serology assay to simultaneously measure antibody responses to 11 F. nucleatum antigens in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI).

    Results: We observed neither a statistically significant colorectal cancer risk association for antibodies to individual F. nucleatum proteins nor for combined positivity to any of the 11 proteins (OR, 0.81; 95% CI, 0.62–1.06).

    Conclusions: Antibody responses to F. nucleatum proteins in prediagnostic serum samples from a subset of colorectal cancer cases and matched controls within the EPIC study were not associated with colorectal cancer risk.

    Impact: Our findings in prospectively ascertained serum samples contradict the existing literature on the association of F. nucleatum with colorectal cancer risk. Future prospective studies, specifically detecting F. nucleatum in stool or tissue biopsies, are needed to complement our findings.

  • 2. Harms, Laura M.
    et al.
    Scalbert, Augustin
    Zamora-Ros, Raul
    Rinaldi, Sabina
    Jenab, Mazda
    Murphy, Neil
    Achaintre, David
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Mancini, Francesca Romana
    Mahamat-Saleh, Yahya
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Katzke, Verena
    Trichopoulou, Antonia
    Martimianaki, Georgia
    Karakatsani, Anna
    Palli, Domenico
    Panico, Salvatore
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel C. H.
    Weiderpass, Elisabete
    Nost, Therese Haugdahl
    Lasheras, Cristina
    Rodriguez-Barranco, Miguel
    Maria Huerta, Jose
    Barricarte, Aurelio
    Dorronsoro, Miren
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Schmidt, Julie A.
    Gunter, Marc
    Riboli, Elio
    Aleksandrova, Krasimira
    Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations: a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2020Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 123, nr 2, s. 198-208, artikkel-id PII S0007114519002538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0 center dot 66, 95 % CI 0 center dot 46, 0 center dot 96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0 center dot 58, 95 % CI 0 center dot 39, 0 center dot 86), 3,4-dihydroxyphenylpropionic acid (OR 0 center dot 63, 95 % CI 0 center dot 46, 0 center dot 87), ferulic acid (OR 0 center dot 65, 95 % CI 0 center dot 44, 0 center dot 96) and caffeic acid (OR 0 center dot 69, 95 % CI 0 center dot 51, 0 center dot 93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0 center dot 67, 95 % CI 0 center dot 48, 0 center dot 93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.

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  • 3. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    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 Populations2019Inngår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, nr 6, s. 1047-1055Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
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  • 4. Li, Chen
    et al.
    Stoma, Svetlana
    Lotta, Luca A.
    Warner, Sophie
    Albrecht, Eva
    Allione, Alessandra
    Arp, Pascal P.
    Broer, Linda
    Buxton, Jessica L.
    Da Silva Couto Alves, Alexessander
    Deelen, Joris
    Fedko, Iryna O.
    Gordon, Scott D.
    Jiang, Tao
    Karlsson, Robert
    Kerrison, Nicola
    Loe, Taylor K.
    Mangino, Massimo
    Milaneschi, Yuri
    Miraglio, Benjamin
    Pervjakova, Natalia
    Russo, Alessia
    Surakka, Ida
    van der Spek, Ashley
    Verhoeven, Josine E.
    Amin, Najaf
    Beekman, Marian
    Blakemore, Alexandra I.
    Canzian, Federico
    Hamby, Stephen E.
    Hottenga, Jouke-Jan
    Jones, Peter D.
    Jousilahti, Pekka
    Mägi, Reedik
    Medland, Sarah E.
    Montgomery, Grant W.
    Nyholt, Dale R.
    Perola, Markus
    Pietiläinen, Kirsi H.
    Salomaa, Veikko
    Sillanpää, Elina
    Suchiman, H. Eka
    van Heemst, Diana
    Willemsen, Gonneke
    Agudo, Antonio
    Boeing, Heiner
    Boomsma, Dorret I.
    Chirlaque, Maria-Dolores
    Fagherazzi, Guy
    Ferrari, Pietro
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502 Malmö Sweden.
    Gieger, Christian
    Eriksson, Johan Gunnar
    Gunter, Marc
    Hagg, Sara
    Hovatta, Iiris
    Imaz, Liher
    Kaprio, Jaakko
    Kaaks, Rudolf
    Key, Timothy
    Krogh, Vittorio
    Martin, Nicholas G.
    Melander, Olle
    Metspalu, Andres
    Moreno, Concha
    Onland-Moret, N. Charlotte
    Nilsson, Peter
    Ong, Ken K.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Pedersen, Nancy L.
    Penninx, Brenda W. J. H.
    Quirós, J. Ramón
    Riitta Jarvelin, Marjo
    Rodríguez-Barranco, Miguel
    Scott, Robert A.
    Severi, Gianluca
    Slagboom, P. Eline
    Spector, Tim D.
    Tjonneland, Anne
    Trichopoulou, Antonia
    Tumino, Rosario
    Uitterlinden, André G.
    van der Schouw, Yvonne T.
    van Duijn, Cornelia M.
    Weiderpass, Elisabete
    Denchi, Eros Lazzerini
    Matullo, Giuseppe
    Butterworth, Adam S.
    Danesh, John
    Samani, Nilesh J.
    Wareham, Nicholas J.
    Nelson, Christopher P.
    Langenberg, Claudia
    Codd, Veryan
    Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length2020Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 106, nr 3, s. 389-404Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.

    Fulltekst (pdf)
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  • 5. Naudin, Sabine
    et al.
    Margalef, Marta Solans
    Hosnijeh, Fatemeh Saberi
    Nieters, Alexandra
    Kyro, Cecilie
    Tjonneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Mahamat-Saleh, Yahya
    Besson, Caroline
    Boutron-Ruault, Marie-Christine
    Kuehn, Tilman
    Canzian, Federico
    Schulze, Matthias B.
    Peppa, Eleni
    Karakatsani, Anna
    Trichopoulou, Antonia
    Sieri, Sabina
    Masala, Giovana
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Chen, Sairah L. F.
    Barroso, Leila L.
    Huerta, Jose M.
    Sanchez, Maria-Jose
    Ardanaz, Eva
    Menendez, Virginia
    Exezarreta, Pilar Amiano
    Späth, Florentin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Jerkeman, Mats
    Jirstom, Karin
    Schmidt, Julie A.
    Aune, Dagfinn
    Weiderpass, Elisabete
    Riboli, Elio
    Vermeulen, Roel
    Casabonne, Delphine
    Gunter, Marc
    Brennan, Paul
    Ferrari, Pietro
    Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study2020Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this rk, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and n-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the ropean Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases 32 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow- . The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, ysical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox oportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence terval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI ore. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the ore equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly iven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD crement equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL btypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

  • 6. Obon-Santacana, Mireia
    et al.
    Lujan-Barroso, Leila
    Freisling, Heinz
    Naudin, Sabine
    Boutron-Ruault, Marie-Christine
    Mancini, Francesca Romana
    Rebours, Vinciane
    Kuehn, Tilman
    Katzke, Verena
    Boeing, Heiner
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Lasheras, Cristina
    Rodriguez-Barranco, Miguel
    Amiano, Pilar
    Santiuste, Carmen
    Ardanaz, Eva
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Schmidt, Julie A.
    Aune, Dagfinn
    Trichopoulou, Antonia
    Thriskos, Paschalis
    Peppa, Eleni
    Masala, Giovanna
    Grioni, Sara
    Tumino, Rosario
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Sciannameo, Veronica
    Vermeulen, Roel
    Sonestedt, Emily
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Weiderpass, Elisabete
    Skeie, Guri
    Gonzalez, Carlos A.
    Riboli, Elio
    Duell, Eric J.
    Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition2020Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 1, s. 76-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72-1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.

  • 7. Papadimitriou, Nikos
    et al.
    Muller, David
    van den Brandt, Piet A.
    Geybels, Milan
    Patel, Chirag J.
    Gunter, Marc J.
    Lopez, David S.
    Key, Timothy J.
    Perez-Cornago, Aurora
    Ferrari, Pietro
    Vineis, Paolo
    Weiderpass, Elisabete
    Boeing, Heiner
    Agudo, Antonio
    Sanchez, Maria-Jose
    Overvad, Kim
    Kuehn, Tilman
    Fortner, Renee T.
    Palli, Domenico
    Drake, Isabel
    Bjartell, Anders
    Santiuste, Carmen
    Bueno-de-Mesquita, Bas H.
    Krogh, Vittorio
    Tjonneland, Anne
    Lauritzen, Dorthe Furstrand
    Gurrea, Aurelio Barricarte
    Quiros, Jose Ramon
    Stattin, Par
    Trichopoulou, Antonia
    Martimianaki, Georgia
    Karakatsani, Anna
    Thysell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ricceri, Fulvio
    Tumino, Rosario
    Larranaga, Nerea
    Khaw, Kay Tee
    Riboli, Elio
    Tzoulaki, Ioanna
    Tsilidis, Konstantinos K.
    A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study2019Inngår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive.

    Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS).

    Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS.

    Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.

    Fulltekst (pdf)
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  • 8.
    Rolandsson, Olov
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hampe, Christiane S.
    Sharp, Stephen J.
    Ardanaz, Eva
    Boeing, Heiner
    Fagherazzi, Guy
    Mancini, Francesca Romana
    Nilsson, Peter M.
    Overvad, Kim
    Chirlaque, Maria-Dolores
    Dorronsoro, Miren
    Gunter, Marc J.
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Krogh, Vittorio
    Kuehn, Tilman
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Severi, Gianluca
    Spijkerman, Annemieke M. W.
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Riboli, Elio
    Forouhi, Nita G.
    Langenberg, Claudia
    Wareham, Nicholas J.
    Autoimmunity plays a role in the onset of diabetes after 40 years of age2019Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.

    Methods: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.

    Results: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.

    Conclusions/interpretation: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

    Fulltekst (pdf)
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  • 9. 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 universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    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 Women2019Inngår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 6, s. 1076-1085Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 10. Trabert, Britton
    et al.
    Tworoger, Shelley S.
    O'Brien, Katie M.
    Townsend, Mary K.
    Fortner, Renee T.
    Iversen, Edwin S.
    Hartge, Patricia
    White, Emily
    Amiano, Pilar
    Arslan, Alan A.
    Bernstein, Leslie
    Brinton, Louise A.
    Buring, Julie E.
    Dossus, Laure
    Fraser, Gary E.
    Gaudet, Mia M.
    Giles, Graham G.
    Gram, Inger T.
    Harris, Holly R.
    Bolton, Judith Hoffman
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Jones, Michael E.
    Kaaks, Rudolf
    Kirsh, Victoria A.
    Knutsen, Synnove F.
    Kvaskoff, Marina
    Lacey, James, V
    Lee, I-Min
    Milne, Roger L.
    Onland-Moret, N. Charlotte
    Overvad, Kim
    Patel, Alpa, V
    Peters, Ulrike
    Poynter, Jenny N.
    Riboli, Elio
    Robien, Kim
    Rohan, Thomas E.
    Sandler, Dale P.
    Schairer, Catherine
    Schouten, Leo J.
    Setiawan, Veronica W.
    Swerdlow, Anthony J.
    Travis, Ruth C.
    Trichopoulou, Antonia
    van den Brandt, Piet A.
    Visvanathan, Kala
    Wilkens, Lynne R.
    Wolk, Alicja
    Zeleniuch-Jacquotte, Anne
    Wentzensen, Nicolas
    The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)2020Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, nr 5, s. 1210-1218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60–2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10–1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04–1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09–1.17)], endometrioid [1.20 (1.10–1.32)], and clear cell [1.37 (1.18–1.58)], but not mucinous [0.99 (0.88–1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies.

    Significance: Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.

  • 11. 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 universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Aune, Dagfinn
    Riboli, Elio
    Cross, Amanda J.
    Gallstones and incident colorectal cancer in a large pan-European cohort study2019Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, nr 6, s. 1510-1516Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 12. 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 universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    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) cohort2019Inngår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 73, nr 8, s. 1122-1132Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 13. Zamora-Ros, Raul
    et al.
    Alghamdi, Muath A.
    Cayssials, Valerie
    Franceschi, Silvia
    Almquist, Martin
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Tsilidis, Konstantinos K.
    Weiderpass, Elisabete
    Boutron-Ruault, Marie-Christine
    Hammer Bech, Bodil
    Overvad, Kim
    Tjonneland, Anne
    Petersen, Kristina E. N.
    Mancini, Francesca Romana
    Mahamat-Saleh, Yahya
    Bonnet, Fabrice
    Kuehn, Tilman
    Fortner, Renee T.
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    Martimianaki, Georgia
    Masala, Giovanna
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Fasanelli, Francesca
    Skeie, Guri
    Braaten, Tonje
    Lasheras, Cristina
    Salamanca-Fernandez, Elena
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Manjer, Jonas
    Wallstrom, Peter
    Bueno-de-Mesquita, H. Bas
    Peeters, Petra H.
    Khaw, Kay-Thee
    Wareham, Nicholas J.
    Schmidt, Julie A.
    Aune, Dagfinn
    Byrnes, Graham
    Scalbert, Augustin
    Agudo, Antonio
    Rinaldi, Sabina
    Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study2019Inngår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 58, nr 8, s. 3303-3312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.

    Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires.

    Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases.

    Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

  • 14. Zamora-Ros, Raul
    et al.
    Cayssials, Valerie
    Franceschi, Silvia
    Kyrø, Cecilie
    Weiderpass, Elisabete
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    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) cohort2019Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 15. 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 universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    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 Study2019Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 4, s. 1293-1303Artikkel i tidsskrift (Fagfellevurdert)
    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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