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  • 1. Butt, Julia
    et al.
    Jenab, Mazda
    Pawlita, Michael
    Tjonneland, Anne
    Kyro, Cecilie
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Dong, Catherine
    Kaaks, Rudolf
    Kuhn, Tilman
    Boeing, Heiner
    Schulze, Matthias B.
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel
    Gram, Inger T.
    Weiderpass, Elisabete
    Borch, Kristin Benjaminsen
    Quiros, Jose Ramon
    Agudo, Antonio
    Rodriguez-Barranco, Miguel
    Santiuste, Carmen
    Ardanaz, Eva
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Imaz, Liher
    Perez-Cornago, Aurora
    Gunter, Marc J.
    Zouiouich, Semi
    Park, Jin Young
    Riboli, Elio
    Cross, Amanda J.
    Heath, Alicia K.
    Waterboer, Tim
    Hughes, David J.
    Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 7, s. 1475-1481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.

    Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.

    Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

  • 2. Cai, Lina
    et al.
    Wheeler, Eleanor
    Kerrison, Nicola D.
    Luan, Jian'an
    Deloukas, Panos
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502, Malmö, Sweden.
    Amiano, Pilar
    Ardanaz, Eva
    Bonet, Catalina
    Fagherazzi, Guy
    Groop, Leif C.
    Kaaks, Rudolf
    Huerta, Jose Maria
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Pala, Valeria
    Panico, Salvatore
    Rodriguez-Barranco, Miguel
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Schulze, Matthias B.
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Riboli, Elio
    McCarthy, Mark I.
    Barroso, Ines
    Langenberg, Claudia
    Wareham, Nicholas J.
    Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study2020Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 7, nr 1, artikel-id 393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.

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  • 3. Cervenka, Iris
    et al.
    Al Rahmoun, Marie
    Mahamat-Saleh, Yahya
    Fournier, Agnes
    Boutron-Ruault, Marie-Christine
    Severi, Gianluca
    Caini, Saverio
    Palli, Domenico
    Ghiasvand, Reza
    Veierod, Marit B.
    Botteri, Edoardo
    Tjonneland, Anne
    Olsen, Anja
    Fortner, Renee T.
    Kaaks, Rudolf
    Schulze, Matthias B.
    Panico, Salvatore
    Trichopoulou, Antonia
    Dessinioti, Clio
    Niforou, Katerina
    Sieri, Sabina
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Sandanger, Torkjel M.
    Colorado-Yohar, Sandra
    Sanchez, Maria J.
    Gil Majuelo, Leire
    Lujan-Barroso, Leila
    Ardanaz, Eva
    Merino, Susana
    Isaksson, Karolin
    Butt, Salma
    Ljuslinder, Ingrid
    Jansson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Weiderpass, Elisabete
    Dossus, Laure
    Rinaldi, Sabina
    Kvaskoff, Marina
    Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 12, s. 3267-3280Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

  • 4. Christakoudi, Sofia
    et al.
    Tsilidis, Konstantinos K.
    Muller, David C.
    Freisling, Heinz
    Weiderpass, Elisabete
    Overvad, Kim
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Pischon, Tobias
    Dahm, Christina C.
    Zhang, Jie
    Tjonneland, Anne
    Halkjaer, Jytte
    MacDonald, Conor
    Boutron-Ruault, Marie-Christine
    Mancini, Francesca Romana
    Kuehn, Tilman
    Kaaks, Rudolf
    Schulze, Matthias B.
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Masala, Giovanna
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Quiros, J. Ramon
    Agudo, Antonio
    Sanchez, Maria-Jose
    Cirera, Lluis
    Barricarte-Gurrea, Aurelio
    Amiano, Pilar
    Memarian, Ensieh
    Sonestedt, Emily
    Bueno-de-Mesquita, Bas
    May, Anne M.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Tong, Tammy Y. N.
    Huybrechts, Inge
    Noh, Hwayoung
    Aglago, Elom K.
    Ellingjord-Dale, Merete
    Ward, Heather A.
    Aune, Dagfinn
    Riboli, Elio
    A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 14541Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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(2)) or obese (BMI<greater than or equal to>30 kg/m(2)) 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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  • 5. Deschasaux, Melanie
    et al.
    Huybrechts, Inge
    Julia, Chantal
    Hercberg, Serge
    Egnell, Manon
    Srour, Bernard
    Kesse-Guyot, Emmanuelle
    Latino-Martel, Paule
    Biessy, Carine
    Casagrande, Corinne
    Murphy, Neil
    Jenab, Mazda
    Ward, Heather A.
    Weiderpass, Elisabete
    Overvad, Kim
    Tjonneland, Anne
    Rostgaard-Hansen, Agnetha Linn
    Boutron-Ruault, Marie-Christine
    Mancini, Francesca Romana
    Mahamat-Saleh, Yahya
    Kuehn, Tilman
    Katzke, Verena
    Bergmann, Manuela M.
    Schulze, Matthias B.
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Masala, Giovanna
    Agnoli, Claudia
    De Magistris, Maria Santucci
    Tumino, Rosario
    Sacerdote, Carlotta
    Boer, Jolanda M. A.
    Verschuren, W. M. Monique
    van der Schouw, Yvonne T.
    Skeie, Guri
    Braaten, Tonje
    Luisa Redondo, M.
    Agudo, Antonio
    Petrova, Dafina
    Colorado-Yohar, Sandra M.
    Barricarte, Aurelio
    Amiano, Pilar
    Sonestedt, Emily
    Ericson, Ulrika
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Sundström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Wareham, Nicholas J.
    Forouhi, Nita G.
    Vineis, Paolo
    Tsilidis, Konstantinos K.
    Knuppel, Anika
    Papier, Keren
    Ferrari, Pietro
    Riboli, Elio
    Gunter, Marc J.
    Touvier, Mathilde
    Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries2020Ingår i: The BMJ, E-ISSN 1756-1833, Vol. 370, artikel-id m3173Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN Population based cohort study. SETTING European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P(0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P(0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P(0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.

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  • 6. Gentiluomo, Manuel
    et al.
    Katzke, Verena A.
    Kaaks, Rudolf
    Tjonneland, Anne
    Severi, Gianluca
    Perduca, Vittorio
    Boutron-Ruault, Marie-Christine
    Weiderpass, Elisabete
    Ferrari, Pietro
    Johnson, Theron
    Schulze, Matthias B.
    Bergmann, Manuela
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Bas
    Vermeulen, Roel
    Sandanger, Torkjel M.
    Quiros, J. Ramon
    Rodriguez-Barranco, Miguel
    Amiano, Pilar
    Colorado-Yohar, Sandra
    Ardanaz, Eva
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Schmidt, Julie A.
    Jakszyn, Paula
    Morelli, Luca
    Canzian, Federico
    Campa, Daniele
    Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 3, s. 681-686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be sociated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma DAC) are very limited.

    Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a antitative real-time PCR assay in peripheral leukocyte samples of 476PDACcases and 357 controls sted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Results: We observed lower mtDNA copy number with advancing age (P = 6.54 x 10(-5)) and with a high dy mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol nsumption. We found an association between increased mtDNA copy number and decreased risk of veloping PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.160.79; P = 0.01] when mparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 5% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an sociation between high mtDNA copy number and decreased risk in the stratum of normal weight, nsistent with the main analyses.

    Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in ripheral blood leukocytes, on PDAC risk.

    Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic ncer.

  • 7. Hampe, Christiane S.
    et al.
    Sahabandu, Diomira
    Kaiser, Vivien
    Telieps, Tanja
    Smeeth, Liam
    Agyemang, Charles
    Spranger, Joachim
    Schulze, Matthias B.
    Mockenhaupt, Frank P.
    Danquah, Ina
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Geographic location determines beta-cell autoimmunity among adult Ghanaians: Findings from the RODAM study2020Ingår i: Immunity, Inflammation and Disease, E-ISSN 2050-4527, Vol. 8, nr 3, s. 299-309Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Beta‐cell autoantibodies are established markers of autoimmunity, which we compared between Ghanaian adults with or without diabetes, living in rural and urban Ghana and in three European cities.

    Methods: In the multicenter cross‐sectional Research on Obesity and Diabetes among African Migrants (RODAM) study (N = 5898), we quantified autoantibodies against glutamic acid decarboxylase (GAD65Ab) by radioligand binding assay (RBA) and established cut‐offs for positivity by displacement analysis. In a subsample, we performed RBA for zinc transporter‐8 autoantibodies (ZnT8Ab). Associations of environmental, sociodemographic, and clinical factors with GAD65Ab were calculated.

    Results: In this study population (age: 46.1 ± 11.9 years; female: 62%; Ghana‐rural: 1111; Ghana‐urban: 1455; Europe: 3332), 9.2% had diabetes with adult‐onset. GAD65Ab concentrations were the highest in Ghana‐rural (32.4; 10.8‐71.3 U/mL), followed by Ghana‐urban (26.0; 12.3‐49.1 U/mL) and Europe (11.9; 3.0‐22.8 U/mL) with no differences between European cities. These distributions were similar for ZnT8Ab. Current fever, history of fever, and higher concentrations of liver enzymes marginally explained site‐specific GAD65Ab concentrations. GAD65Ab positivity was as frequent in diabetes as in nondiabetes (5.4% vs 6.1%;  = .25). This was also true for ZnT8Ab positivity.

    Conclusion: Geographic location determines the occurrence of GAD65Ab and ZnT8Ab more than the diabetes status. Beta‐cell autoimmunity may not be feasible to differentiate diabetes subgroups in this population.

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  • 8. Ibsen, Daniel B.
    et al.
    Steur, Marinka
    Imamura, Fumiaki
    Overvad, Kim
    Schulze, Matthias B.
    Bendinelli, Benedetta
    Guevara, Marcela
    Agudo, Antonio
    Amiano, Pilar
    Aune, Dagfinn
    Barricarte, Aurelio
    Ericson, Ulrika
    Fagherazzi, Guy
    Franks, Paul W.
    Freisling, Heinz
    Quiros, Jose R.
    Grioni, Sara
    Heath, Alicia K.
    Huybrechts, Inge
    Katze, Verena
    Laouali, Nasser
    Mancini, Francesca
    Masala, Giovanna
    Olsen, Anja
    Papier, Keren
    Ramne, Stina
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sánchez, Maria-José
    Santiuste, Carmen
    Simeon, Vittorio
    Spijkerman, Annemieke M. W.
    Srour, Bernard
    Tjønneland, Anne
    Tong, Tammy Y. N.
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Weiderpass, Elisabete
    Wittenbecher, Clemens
    Sharp, Stephen J.
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nick J.
    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 Study2020Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 43, nr 11, s. 2660-2667Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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.

  • 9. Kliemann, Nathalie
    et al.
    Murphy, Neil
    Viallon, Vivian
    Freisling, Heinz
    Tsilidis, Konstantinos K.
    Rinaldi, Sabina
    Mancini, Francesca R.
    Fagherazzi, Guy
    Boutron-Ruault, Marie-Christine
    Boeing, Heiner
    Schulze, Matthias B.
    Masala, Giovanna
    Krogh, Vittorio
    Sacerdote, Carlotta
    de Magistris, Maria S.
    Bueno-de-Mesquita, Bas
    Weiderpass, Elisabete
    Kuehn, Tilman
    Kaaks, Rudolf
    Jakszyn, Paula
    Redondo-Sanchez, Daniel
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Gurrea, Aurelio B.
    Ericson, Ulrica
    Drake, Isabel
    Nost, Therese H.
    Aune, Dagfinn
    May, Anne M.
    Tjonneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Tumino, Rosario
    Quiros, Jose R.
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Nilsson, Lena M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Riboli, Elio
    Huybrechts, Inge
    Gunter, Marc J.
    Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 147, nr 3, s. 648-661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness.

  • 10. Kroeger, Janine
    et al.
    Meidtner, Karina
    Stefan, Norbert
    Guevara, Marcela
    Kerrison, Nicola D.
    Ardanaz, Eva
    Aune, Dagfinn
    Boeing, Heiner
    Dorronsoro, Miren
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden .
    Freisling, Heinz
    Gunter, Marc J.
    Huerta, José Maria
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay Tee
    Krogh, Vittorio
    Kuehn, Tilman
    Mancini, Francesca Romana
    Mattiello, Amalia
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sala, Nuria
    Salamanca-Fernandez, Elena
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    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.
    Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis2018Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 67, nr 6, s. 1200-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (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 case subjects. A genetic score of the AHSG single nucleotide polymorphisms 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 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 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 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.

  • 11. Löfvenborg, Josefin E.
    et al.
    Carlsson, Sofia
    Andersson, Tomas
    Hampe, Christiane S.
    Koulman, Albert
    Chirlaque Lopez, María Dolores
    Jakszyn, Paula
    Katzke, Verena A.
    Kühn, Tilman
    Kyrø, Cecilie
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Sánchez, Maria-Jose
    van der Schouw, Yvonne
    Schulze, Matthias B.
    Tjønneland, Anne
    Weiderpass, Elisabete
    Riboli, Elio
    Forouhi, Nita G.
    Sharp, Stephen J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Wareham, Nicholas J.
    Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study2021Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, nr 2, s. 416-424Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.

    RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.

    RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76–3.63] and 2.48 [1.79–3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16–0.72] and 0.48 [0.24–0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70–6.72]) and an AP of 0.46 (0.12–0.80) compared with antibody-negative individuals with high n-3 PUFAs.

    CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

  • 12. Sieri, Sabina
    et al.
    Agnoli, Claudia
    Grioni, Sara
    Weiderpass, Elisabete
    Mattiello, Amalia
    Sluijs, Ivonne
    Sanchez, Maria Jose
    Jakobsen, Marianne Uhre
    Sweeting, Michael
    van der Schouw, Yvonne T.
    Nilsson, Lena Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Katzke, Verena A.
    Kuhn, Tilman
    Overvad, Kim
    Tong, Tammy Y. N.
    Conchi, Moreno-Iribas
    Ramon Quiros, Jose
    Manuel Garcia-Torrecillas, Juan
    Mokoroa, Olatz
    Gomez, Jesus-Humberto
    Tjonneland, Anne
    Sonestedt, Emiliy
    Trichopoulou, Antonia
    Karakatsani, Anna
    Valanou, Elissavet
    Boer, Jolanda M. A.
    Verschuren, W. M. Monique
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Madika, Anne-Laure
    Bergmann, Manuela M.
    Schulze, Matthias B.
    Ferrari, Pietro
    Freisling, Heinz
    Lennon, Hannah
    Sacerdote, Carlotta
    Masala, Giovanna
    Tumino, Rosario
    Riboli, Elio
    Wareham, Nicholas J.
    Danesh, John
    Forouhi, Nita G.
    Butterworth, Adam S.
    Krogh, Vittorio
    Glycemic index, glycemic load, and risk of coronary heart disease: a pan-European cohort study2020Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 112, nr 3, s. 631-643Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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/m(2)) >= 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.

  • 13. Van Puyvelde, Heleen
    et al.
    Perez-Cornago, Aurora
    Casagrande, Corinne
    Nicolas, Genevieve
    Versele, Vicka
    Skeie, Guri
    B. Schulze, Matthias
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Maria Huerta, Jose
    Oliverio, Andreina
    Ricceri, Fulvio
    Halkjaer, Jytte
    Amiano Etxezarreta, Pilar
    Van Herck, Koen
    Weiderpass, Elisabete
    J. Gunter, Marc
    Huybrechts, Inge
    Comparing Calculated Nutrient Intakes Using Different Food Composition Databases: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort2020Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 12, nr 10, artikel-id 2906Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study aimed to compare calculated nutrient intakes from two different food composition databases using data from the European prospective investigation into cancer and nutrition (EPIC) cohort. Dietary intake data of the EPIC cohort was recently matched to 150 food components from the U.S. nutrient database (USNDB). Twenty-eight of these nutrients were already included in the EPIC nutrient database (ENDB-based upon country specific food composition tables), and used for comparison. Paired sample t-tests, Pearson's correlations (r), weighted kappa's (kappa) and Bland-Altman plots were used to compare the dietary intake of 28 nutrients estimated by the USNDB and the ENDB for 476,768 participants. Small but significant differences were shown between the USNDB and the ENDB for energy and macronutrient intakes. Moderate to very strong correlations (r = 0.60-1.00) were found for all macro- and micronutrients. A strong agreement (kappa > 0.80) was found for energy, water, total fat, carbohydrates, sugar, alcohol, potassium and vitamin C, whereas a weak agreement (kappa < 0.60) was found for starch, vitamin D and vitamin E. Dietary intakes estimated via the USNDB compare adequately with those obtained via the ENDB for most macro- and micronutrients, although the agreement was weak for starch, vitamin D and vitamin E. The USNDB will allow exposure assessments for 150 nutrients to investigate associations with disease outcomes within the EPIC cohort.

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  • 14. Yammine, Sahar
    et al.
    Huybrechts, Inge
    Biessy, Carine
    Dossus, Laure
    Aglago, Elom K.
    Naudin, Sabine
    Ferrari, Pietro
    Weiderpass, Elisabete
    Tjonneland, Anne
    Hansen, Louise
    Overvad, Kim
    Mancini, Francesca R.
    Boutron-Ruault, Marie-Christine
    Kvaskoff, Marina
    Fortner, Renee T.
    Kaaks, Rudolf
    Schulze, Matthias B.
    Boeing, Heiner
    Trichopoulou, Antonia
    Karakatsani, Anna
    La Vecchia, Carlo
    Benetou, Vassiliki
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Macciotta, Alessandra
    Gram, Inger T.
    Skeie, Guri
    Quiros, Jose R.
    Agudo, Antonio
    Sanchez, Maria-Jose
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Gil, Leire
    Sartor, Hanna
    Drake, Isabel
    Idahl, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Aune, Dagfinn
    Ward, Heather
    Merritt, Melissa A.
    Allen, Naomi E.
    Gunter, Marc J.
    Chajes, Veronique
    Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 9, s. 1739-1749Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer.

    Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis.

    Results: Apositive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintile(Q5-Q1) = 1.29; 95% confidence interval (CI) = 1.03-1.62; P-trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P-trend = 0.03) and n-3 alpha-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P-trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertile(T3-T1) = 1.39; 95% CI = 0.99-1.94; P-trend = 0.06) anda-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P-trend = 0.06).

    Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and alpha-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer.

    Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.

  • 15. Zamora-Ros, Raul
    et al.
    Lujan-Barroso, Leila
    Achaintre, David
    Franceschi, Silvia
    Kyro, Cecilie
    Overvad, Kim
    Tjonneland, Anne
    Truong, Therese
    Lecuyer, Lucie
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Johnson, Theron S.
    Schulze, Matthias B.
    Trichopoulou, Antonia
    Peppa, Eleni
    La Vechia, Carlo
    Masala, Giovanna
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Skeie, Guri
    Quiros, J. Ramon
    Rodriguez-Barranco, Miguel
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Almquist, Martin
    Hennings, Joakim
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Vermeulen, Roel
    Wareham, Nicholas J.
    Tong, Tammy Y. N.
    Aune, Dagfinn
    Byrnes, Graham
    Weiderpass, Elisabete
    Scalbert, Augustin
    Rinaldi, Sabina
    Agudo, Antonio
    Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study2021Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 113, nr 1, s. 162-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.

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