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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 Cancer2019Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 9, s. 1552-1555Artikel i tidskrift (Refereegranskat)
    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. 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. Christakoudi, Sofia
    et al.
    Pagoni, Panagiota
    Ferrari, Pietro
    Cross, Amanda J.
    Tzoulaki, Ioanna
    Muller, David C.
    Weiderpass, Elisabete
    Freisling, Heinz
    Murphy, Neil
    Dossus, Laure
    Turzanski Fortner, Renee
    Agudo, Antonio
    Overvad, Kim
    Perez-Cornago, Aurora
    Key, Timothy J.
    Brennan, Paul
    Johansson, Mattias
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Artaud, Fanny
    Severi, Gianluca
    Kaaks, Rudolf
    Schulze, Matthias B.
    Bergmann, Manuela M.
    Masala, Giovanna
    Grioni, Sara
    Simeon, Vittorio
    Tumino, Rosario
    Sacerdote, Carlotta
    Skeie, Guri
    Rylander, Charlotta
    Borch, Kristin Benjaminsen
    Quirós, J. Ramón
    Rodriguez-Barranco, Miguel
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Amiano, Pilar
    Drake, Isabel
    Stocks, Tanja
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Science, Uppsala University, Uppsala, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ellingjord-Dale, Merete
    Riboli, Elio
    Tsilidis, Konstantinos K.
    Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2021Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, nr 7, s. 1637-1651Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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  • 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. 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) cohort2020Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 123, nr 2, s. 198-208, artikel-id PII S0007114519002538Artikel i tidskrift (Refereegranskat)
    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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  • 7. 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.

  • 8. 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 Populations2019Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, nr 6, s. 1047-1055Artikel i tidskrift (Refereegranskat)
    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.

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  • 9. Ji, Xuemei
    et al.
    Mukherjee, Semanti
    Landi, Maria Teresa
    Bosse, Yohan
    Joubert, Philippe
    Zhu, Dakai
    Gorlov, Ivan
    Xiao, Xiangjun
    Han, Younghun
    Gorlova, Olga
    Hung, Rayjean J.
    Brhane, Yonathan
    Carreras-Torres, Robert
    Christiani, David C.
    Caporaso, Neil
    Johansson, Mattias
    Liu, Geoffrey
    Bojesen, Stig E.
    Le Marchand, Loic
    Albanes, Demetrios
    Bickeboeller, Heike
    Aldrich, Melinda C.
    Bush, William S.
    Tardon, Adonina
    Rennert, Gad
    Chen, Chu
    Byun, Jinyoung
    Dragnev, Konstantin H.
    Field, John K.
    Kiemeney, Lambertus F. A.
    Lazarus, Philip
    Zienolddiny, Shan
    Lam, Stephen
    Schabath, Matthew B.
    Andrew, Angeline S.
    Bertazzi, Pier A.
    Pesatori, Angela C.
    Diao, Nancy
    Su, Li
    Song, Lei
    Zhang, Ruyang
    Leighl, Natasha
    Johansen, Jakob S.
    Mellemgaard, Anders
    Saliba, Walid
    Haiman, Christopher
    Wilkens, Lynne
    Fernandez-Somoano, Ana
    Fernandez-Tardon, Guillermo
    van der Heijden, Erik H. F. M.
    Kim, Jin Hee
    Davies, Michael P. A.
    Marcus, Michael W.
    Brunnstrom, Hans
    Manjer, Jonas
    Melander, Olle
    Muller, David C.
    Overvad, Kim
    Trichopoulou, Antonia
    Tumino, Rosario
    Goodman, Gary E.
    Cox, Angela
    Taylor, Fiona
    Woll, Penella
    Wichmann, Erich
    Muley, Thomas
    Risch, Angela
    Rosenberger, Albert
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Tsao, Ming-Sound
    Shepherd, Frances
    Arnold, Susanne M.
    Haura, Eric B.
    Bolca, Ciprian
    Holcatova, Ivana
    Janout, Vladimir
    Kontic, Milica
    Lissowska, Jolanta
    Mukeria, Anush
    Ognjanovic, Simona
    Orlowski, Tadeusz M.
    Scelo, Ghislaine
    Swiatkowska, Beata
    Zaridze, David
    Bakke, Per
    Skaug, Vidar
    Butler, Lesley M.
    Offit, Kenneth
    Srinivasan, Preethi
    Bandlamudi, Chaitanya
    Hellmann, Matthew D.
    Solit, David B.
    Robson, Mark E.
    Rudin, Charles M.
    Stadler, Zsofia K.
    Taylor, Barry S.
    Berger, Michael F.
    Houlston, Richard
    McLaughlin, John
    Stevens, Victoria
    Nickle, David C.
    Obeidat, 'en
    Timens, Wim
    Artigas, Maria Soler
    Shete, Sanjay
    Brenner, Hermann
    Chanock, Stephen
    Brennan, Paul
    McKay, James D.
    Amos, Christopher, I
    Protein-altering germline mutations implicate novel genes related to lung cancer development2020Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 11, nr 1, artikel-id 2220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

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  • 10. 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.

  • 11. 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, Näringsforskning. 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 Length2020Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 106, nr 3, s. 389-404Artikel i tidskrift (Refereegranskat)
    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.

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  • 12. Lujan-Barroso, Leila
    et al.
    Botteri, Edoardo
    Caini, Saverio
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Roswall, Nina
    Tjonneland, Anne
    Bueno-de-Mesquita, Bas
    Gram, Inger T.
    Tumino, Rosario
    Kiemeney, Lambertus A.
    Liedberg, Fredrik
    Stocks, Tanja
    Gunter, Marc J.
    Murphy, Neil
    Cervenka, Iris
    Fournier, Agnes
    Kvaskoff, Marina
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Surgical Sciences, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden.
    Overvad, Kim
    Lund, Eiliv
    Waaseth, Marit
    Turzanski Fortner, Renee
    Kuhn, Tilman
    Menendez, Virginia
    Sanchez, Maria-Jose
    Santiuste, Carmen
    Perez-Cornago, Aurora
    Zamora-Ros, Raul
    Cross, Amanda J.
    Trichopoulou, Antonia
    Karakatsani, Anna
    Peppa, Eleni
    Palli, Domenico
    Krogh, Vittorio
    Sciannameo, Veronica
    Mattiello, Amalia
    Panico, Salvatore
    van Gils, Carla H.
    Onland-Moret, N. Charlotte
    Barricarte, Aurelio
    Amiano, Pilar
    Khaw, Kay-Tee
    Boeing, Heiner
    Weiderpass, Elisabete
    Duell, Eric J.
    Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: A Prospective Study in the EPIC Cohort2020Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, nr 8, s. 1654-1664Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk.

    Methods: Weused an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models.

    Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR= 5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscleinvasive urothelial carcinoma risk was observed.

    Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk.

    Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

  • 13. 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.

  • 14. Merino, Jordi
    et al.
    Guasch-Ferre, Marta
    Ellervik, Christina
    Dashti, Hassan S.
    Sharp, Stephen J.
    Wu, Peitao
    Overvad, Kim
    Sarnowski, Chloe
    Kuokkanen, Mikko
    Lemaitre, Rozenn N.
    Justice, Anne E.
    Ericson, Ulrika
    Braun, Kim V. E.
    Mahendran, Yuvaraj
    Frazier-Wood, Alexis C.
    Sun, Dianjianyi
    Chu, Audrey Y.
    Tanaka, Toshiko
    Luan, Jian'an
    Hong, Jaeyoung
    Tjonneland, Anne
    Ding, Ming
    Lundqvist, Annamari
    Mukamal, Kenneth
    Rohde, Rebecca
    Schulz, Christina-Alexandra
    Franco, Oscar H.
    Grarup, Niels
    Chen, Yii-Der Ida
    Bazzano, Lydia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliff Department of Medicine, University of Oxford, Oxford, UK.
    Buring, Julie E.
    Langenberg, Claudia
    Liu, Ching-Ti
    Hansen, Torben
    Jensen, Majken K.
    Saaksjarvi, Katri
    Psaty, Bruce M.
    Young, Kristin L.
    Hindy, George
    Sandholt, Camilla Helene
    Ridker, Paul M.
    Ordovas, Jose M.
    Meigs, James B.
    Pedersen, Oluf
    Kraft, Peter
    Perola, Markus
    North, Kari E.
    Orho-Melander, Marju
    Voortman, Trudy
    Toft, Ulla
    Rotter, Jerome I.
    Qi, Lu
    Forouhi, Nita G.
    Mozaffarian, Dariush
    Sorensen, Thorkild I. A.
    Stampfer, Meir J.
    Mannisto, Satu
    Selvin, Elizabeth
    Imamura, Fumiaki
    Salomaa, Veikko
    Hu, Frank B.
    Wareham, Nick J.
    Dupuis, Josee
    Smith, Caren E.
    Kilpelainen, Tuomas O.
    Chasman, Daniel I.
    Florez, Jose C.
    Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis2019Ingår i: BMJ. British Medical Journal, ISSN 0959-8146, E-ISSN 0959-535X, Vol. 366, artikel-id l4292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes.

    DESIGN Individual participant data meta-analysis.

    DATA SOURCES Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators.

    REVIEW METHODS Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score.

    RESULTS Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I-2 = 7.1%, tau(2) = 0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I-2 = 18.0%, tau(2) = 0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I-2 = 58.8%, tau(2) = 0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I-2 = 25.9%, tau(2) = 0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed.

    CONCLUSIONS These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.

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  • 15. Naudin, Sabine
    et al.
    Margalef, Marta Solans
    Hosnijeh, Fatemeh Saberi
    Nieters, Alexandra
    Kyrø, Cecilie
    Tjønneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Mahamat-Saleh, Yahya
    Besson, Caroline
    Boutron-Ruault, Marie-Christine
    Kühn, 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, José M.
    Sánchez, 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 study2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 147, nr 6, s. 1649-1656Artikel i tidskrift (Refereegranskat)
    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.

  • 16. Naudin, Sabine
    et al.
    Viallon, Vivian
    Hashim, Dana
    Freisling, Heinz
    Jenab, Mazda
    Weiderpass, Elisabete
    Perrier, Flavie
    McKenzie, Fiona
    Bueno-de-Mesquita, H. Bas
    Olsen, Anja
    Tjonneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Mancini, Francesca R.
    Rebours, Vinciane
    Boutron-Ruault, Marie-Christine
    Katzke, Verena
    Kaaks, Rudolf
    Bergmann, Manuela
    Boeing, Heiner
    Peppa, Eleni
    Karakatsani, Anna
    Trichopoulou, Antonia
    Pala, Valeria
    Masala, Giovana
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    May, Anne M.
    van Gils, Carla H.
    Rylander, Charlotta
    Borch, Kristin Benjaminsen
    Chirlaque Lopez, Maria Dolores
    Sanchez, Maria-Jose
    Ardanaz, Eva
    Quiros, Jose Ramon
    Amiano Exezarreta, Pilar
    Sund, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Drake, Isabel
    Regner, Sara
    Travis, Ruth C.
    Wareham, Nick
    Aune, Dagfinn
    Riboli, Elio
    Gunter, Marc J.
    Duell, Eric J.
    Brennan, Paul
    Ferrari, Pietro
    Healthy lifestyle and the risk of pancreatic cancer in the EPIC study2020Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 35, nr 10, s. 975-986Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

  • 17. 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, Kirurgi.
    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 Nutrition2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 1, s. 76-84Artikel i tidskrift (Refereegranskat)
    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.

  • 18. 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
    Sánchez, María‑José
    Overvad, Kim
    Kühn, Tilman
    Fortner, Renee T.
    Palli, Domenico
    Drake, Isabel
    Bjartell, Anders
    Santiuste, Carmen
    Bueno-de-Mesquita, Bas H.
    Krogh, Vittorio
    Tjjønneland, Anne
    Lauritzen, Dorthe Furstrand
    Gurrea, Aurelio Barricarte
    Quirós, José Ramón
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    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
    Larrañaga, 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 Study2020Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 59, nr 7, s. 2929-2937Artikel i tidskrift (Refereegranskat)
    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.

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  • 19.
    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 age2020Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, s. 266-277Artikel i tidskrift (Refereegranskat)
    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.

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  • 20. 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 Women2019Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, nr 6, s. 1076-1085Artikel i tidskrift (Refereegranskat)
    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.

  • 21. 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.

  • 22. Stepien, Magdalena
    et al.
    Keski-Rahkonen, Pekka
    Kiss, Agneta
    Robinot, Nivonirina
    Duarte-Salles, Talita
    Murphy, Neil
    Perlemuter, Gabriel
    Viallon, Vivian
    Tjønneland, Anne
    Rostgaard-Hansen, Agnetha Linn
    Dahm, Christina C.
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Mancini, Francesca Romana
    Mahannat-Saleh, Yahya
    Aleksandrova, Krasimira
    Kaaks, Rudolf
    Kühn, Tilman
    Trichopoulou, Antonia
    Karakatsani, Anna
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Tagliabue, Giovanna
    Naccarati, Alessio
    Vermeulen, Roel C. H.
    Bueno-de-Mesquita, Hendrik Bastiaan
    Weiderpass, Elisabete
    Skeie, Guri
    Ramón Quirós, Jose
    Ardanaz, Eva
    Mokoroa, Olatz
    Sala, Núria
    Sánchez, Maria-Jose
    María Huerta, José
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Ohlsson, Bodil
    Sjöberg, Klas
    Schmidt, Julie A.
    Wareham, Nick
    Khaw, Kay-Tee
    Ferrari, Pietro
    Rothwell, Joseph A.
    Gunter, Marc
    Riboli, Elio
    Scalbert, Augustin
    Jenab, Mazda
    Metabolic perturbations prior to hepatocellular carcinoma diagnosis: findings from a prospective observational cohort study2021Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 148, nr 3, s. 609-625Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed forN1-acetylspermidine, isatin,p-hydroxyphenyllactic acid, tyrosine, sphingosine,l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, gamma-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

  • 23. Tong, Tammy Y. N.
    et al.
    Appleby, Paul N.
    Key, Timothy J.
    Dahm, Christina C.
    Overvad, Kim
    Olsen, Anja
    Tjonneland, Anne
    Katzke, Verena
    Kuhn, Tilman
    Boeing, Heiner
    Karakatsani, Anna
    Peppa, Eleni
    Trichopoulou, Antonia
    Weiderpass, Elisabete
    Masala, Giovanna
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Boer, Jolanda M. A.
    Verschuren, W. M. Monique
    Quiros, J. Ramon
    Agudo, Antonio
    Rodriguez-Barranco, Miguel
    Imaz, Liher
    Chirlaque, Maria-Dolores
    Moreno-Iribas, Conchi
    Engstrom, Gunnar
    Sonestedt, Emily
    Lind, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Otten, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Khaw, Kay-Tee
    Aune, Dagfinn
    Riboli, Elio
    Wareham, Nicholas J.
    Imamura, Fumiaki
    Forouhi, Nita G.
    di Angelantonio, Emanuele
    Wood, Angela M.
    Butterworth, Adam S.
    Perez-Cornago, Aurora
    The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries2020Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, nr 28, s. 2632-2640Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.

    Methods and results: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82–0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69–0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91–0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85–0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81–0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96–1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09–1.43, P-trend = 0.002).

    Conclusion: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.

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  • 24. 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)2020Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, nr 5, s. 1210-1218Artikel i tidskrift (Refereegranskat)
    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.

  • 25. 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, Kirurgi.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Aune, Dagfinn
    Riboli, Elio
    Cross, Amanda J.
    Gallstones and incident colorectal cancer in a large pan-European cohort study2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, nr 6, s. 1510-1516Artikel i tidskrift (Refereegranskat)
    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.

  • 26. 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) cohort2019Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 73, nr 8, s. 1122-1132Artikel i tidskrift (Refereegranskat)
    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.

  • 27. 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.

  • 28. 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, Kirurgi.
    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) study2019Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 58, nr 8, s. 3303-3312Artikel i tidskrift (Refereegranskat)
    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.

  • 29. 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, Kirurgi.
    Sandström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    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) cohort2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 7, s. 1841-1850Artikel i tidskrift (Refereegranskat)
    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.

  • 30. 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.

  • 31. 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 Study2019Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, nr 4, s. 1293-1303Artikel i tidskrift (Refereegranskat)
    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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  • 32. Zheng, Ju-Sheng
    et al.
    Luan, Jian'an
    Sofianopoulou, Eleni
    Sharp, Stephen J.
    Day, Felix R.
    Imamura, Fumiaki
    Gundersen, Thomas E.
    Lotta, Luca A.
    Sluijs, Ivonne
    Stewart, Isobel D.
    Shah, Rupal L.
    van der Schouw, Yvonne T.
    Wheeler, Eleanor
    Ardanaz, Eva
    Boeing, Heiner
    Dorronsoro, Miren
    Dahm, Christina C.
    Dimou, Niki
    El-Fatouhi, Douae
    Franks, Paul W.
    Fagherazzi, Guy
    Grioni, Sara
    Huerta, Jose Maria
    Heath, Alicia K.
    Hansen, Louise
    Jenab, Mazda
    Jakszyn, Paula
    Kaaks, Rudolf
    Kuehn, Tilman
    Khaw, Kay-Tee
    Laouali, Nasser
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Olsen, Anja
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rodriguez-Barranco, Miguel
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Tong, Tammy Y. N.
    Tumino, Rosario
    Tsilidis, Konstantinos K.
    Danesh, John
    Riboli, Elio
    Butterworth, Adam S.
    Langenberg, Claudia
    Forouhi, Nita G.
    Wareham, Nicholas J.
    The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis2020Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 17, nr 10, artikel-id e1003394Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.

    Methods and findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.

    Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

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  • 33. Zheng, Ju-Sheng
    et al.
    Sharp, Stephen J.
    Imamura, Fumiaki
    Chowdhury, Rajiv
    Gundersen, Thomas E.
    Steur, Marinka
    Sluijs, Ivonne
    Schouw, Yvonne T. van der
    Agudo, Antonio
    Aune, Dagfinn
    Barricarte, Aurelio
    Boeing, Heiner
    Chirlaque, Maria -Dolores
    Dorronsoro, Miren
    Freisling, Heinz
    El-Fatouhi, Douae
    Franks, Paul W.
    Fagherazzi, Guy
    Grioni, Sara
    Gunter, Marc J.
    Kyro, Cecilie
    Katzke, Verena
    Kuhn, Tilman
    Khaw, Kay-Tee
    Laouali, Nasser
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Papier, Keren
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Redondo-Sanchez, Daniel
    Ricceri, Fulvio
    Schulze, Matthias B.
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tong, Tammy Y. N.
    Tumino, Rosario
    Weiderpass, Elisabete
    John, Danesh
    Butterworth, Adam S.
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries2020Ingår i: The BMJ, E-ISSN 1756-1833, Vol. 370, artikel-id 2194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

    Design: Prospective case-cohort study.

    Setting: Populations from eight European countries.

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

    Main outcome measure: Incident type 2 diabetes.

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

    Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

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