TY - JOUR A1 - Christakoudi, Sofa A1 - Tsilidis, Konstantinos K. A1 - Muller, David C. A1 - Freisling, Heinz A1 - Weiderpass, Elisabete A1 - Overvad, Kim A1 - Söderberg, Stefan A1 - Häggström, Christel A1 - Pischon, Tobias A1 - Dahm, Christina C. A1 - Zhang, Jie A1 - Tjønneland, Anne A1 - Schulze, Matthias Bernd T1 - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort JF - Scientific Reports N2 - 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 (BMI30 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. KW - all-cause mortality KW - anthropometric measures KW - mass index KW - overweight KW - cancer KW - prediction KW - adiposity KW - size Y1 - 2020 VL - 10 IS - 1 PB - Springer Nature CY - Berlin ER - TY - GEN A1 - Christakoudi, Sofa A1 - Tsilidis, Konstantinos K. A1 - Muller, David C. A1 - Freisling, Heinz A1 - Weiderpass, Elisabete A1 - Overvad, Kim A1 - Söderberg, Stefan A1 - Häggström, Christel A1 - Pischon, Tobias A1 - Dahm, Christina C. A1 - Zhang, Jie A1 - Tjønneland, Anne A1 - Schulze, Matthias Bernd T1 - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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 (BMI30 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1200 KW - all-cause mortality KW - anthropometric measures KW - mass index KW - overweight KW - cancer KW - prediction KW - adiposity KW - size Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-525827 SN - 1866-8372 IS - 1 ER - TY - GEN A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Haggstrom, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1373 KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-573609 SN - 1866-8372 IS - 7 ER - TY - JOUR A1 - Christakoudi, Sofia A1 - Pagoni, Panagiota A1 - Ferrari, Pietro A1 - Cross, Amanda J. A1 - Tzoulaki, Ioanna A1 - Muller, David C. A1 - Weiderpass, Elisabete A1 - Freisling, Heinz A1 - Murphy, Neil A1 - Dossus, Laure A1 - Turzanski Fortner, Renee A1 - Agudo, Antonio A1 - Overvad, Kim A1 - Perez-Cornago, Aurora A1 - Key, Timothy J. A1 - Brennan, Paul A1 - Johansson, Mattias A1 - Tjonneland, Anne A1 - Halkjaer, Jytte A1 - Boutron-Ruault, Marie-Christine A1 - Artaud, Fanny A1 - Severi, Gianluca A1 - Kaaks, Rudolf A1 - Schulze, Matthias Bernd A1 - Bergmann, Manuela M. A1 - Masala, Giovanna A1 - Grioni, Sara A1 - Simeon, Vittorio A1 - Tumino, Rosario A1 - Sacerdote, Carlotta A1 - Skeie, Guri A1 - Rylander, Charlotta A1 - Borch, Kristin Benjaminsen A1 - Quiros, J. Ramon A1 - Rodriguez-Barranco, Miguel A1 - Chirlaque, Maria-Dolores A1 - Ardanaz, Eva A1 - Amiano, Pilar A1 - Drake, Isabel A1 - Stocks, Tanja A1 - Häggström, Christel A1 - Harlid, Sophia A1 - Ellingjord-Dale, Merete A1 - Riboli, Elio A1 - Tsilidis, Konstantinos K. T1 - Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - International journal of cancer N2 - 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. KW - BMI change KW - cancer KW - middle adulthood KW - weight gain KW - weight loss Y1 - 2020 U6 - https://doi.org/10.1002/ijc.33339 SN - 0020-7136 SN - 1097-0215 VL - 148 IS - 7 SP - 1637 EP - 1651 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Harms, Laura M. A1 - Scalbert, Augustin A1 - Zamora-Ros, Raul A1 - Rinaldi, Sabina A1 - Jenab, Mazda A1 - Murphy, Neil A1 - Achaintre, David A1 - Tjønneland, Anne A1 - Olsen, Anja A1 - Overvad, Kim A1 - Aleksandrova, Krasimira T1 - Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations BT - a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort JF - British Journal of Nutrition N2 - 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. KW - polyphenols KW - plasma measurements KW - C-reactive protein KW - inflammation KW - chronic diseases Y1 - 2019 U6 - https://doi.org/10.1017/S0007114519002538 SN - 0007-1145 SN - 1475-2662 VL - 123 IS - 2 SP - 198 EP - 208 PB - Cambridge University Press CY - Cambridge ER - TY - GEN A1 - Harms, Laura M. A1 - Scalbert, Augustin A1 - Zamora-Ros, Raul A1 - Rinaldi, Sabina A1 - Jenab, Mazda A1 - Murphy, Neil A1 - Achaintre, David A1 - Tjønneland, Anne A1 - Olsen, Anja A1 - Overvad, Kim A1 - Aleksandrova, Krasimira T1 - Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations BT - a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1404 KW - polyphenols KW - plasma measurements KW - C-reactive protein KW - inflammation KW - chronic diseases Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515774 SN - 1866-8372 IS - 2 ER - TY - JOUR A1 - Jannasch, Franziska A1 - Kröger, Janine A1 - Agnoli, Claudia A1 - Barricarte, Aurelio A1 - Boeing, Heiner A1 - Cayssials, Valérie A1 - Colorado-Yohar, Sandra A1 - Dahm, Christina C. A1 - Dow, Courtney A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Freisling, Heinz A1 - Gunter, Marc J. A1 - Kerrison, Nicola D. A1 - Key, Timothy J. A1 - Khaw, Kay-Tee A1 - Kühn, Tilman A1 - Kyro, Cecilie A1 - Mancini, Francesca Romana A1 - Mokoroa, Olatz A1 - Nilsson, Peter A1 - Overvad, Kim A1 - Palli, Domenico A1 - Panico, Salvatore A1 - Quiros Garcia, Jose Ramon A1 - Rolandsson, Olov A1 - Sacerdote, Carlotta A1 - Sanchez, Maria-Jose A1 - Sahrai, Mohammad Sediq A1 - Schübel, Ruth A1 - Sluijs, Ivonne A1 - Spijkerman, Annemieke M. W. A1 - Tjonneland, Anne A1 - Tong, Tammy Y. N. A1 - Tumino, Rosario A1 - Riboli, Elio A1 - Langenberg, Claudia A1 - Sharp, Stephen J. A1 - Forouhi, Nita G. A1 - Schulze, Matthias Bernd A1 - Wareham, Nicholas J. T1 - Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations JF - The Journal of Nutrition N2 - 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. KW - dietary patterns KW - principal component analysis KW - diet-disease association KW - type 2 diabetes mellitus KW - replication KW - meta-analysis Y1 - 2019 U6 - https://doi.org/10.1093/jn/nxz031 SN - 0022-3166 SN - 1541-6100 VL - 149 IS - 6 SP - 1047 EP - 1055 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Kroeger, Janine A1 - Meidtner, Karina A1 - Stefan, Norbert A1 - Guevara, Marcela A1 - Kerrison, Nicola D. A1 - Ardanaz, Eva A1 - Aune, Dagfinn A1 - Boeing, Heiner A1 - Dorronsoro, Miren A1 - Dow, Courtney A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Freisling, Heinz A1 - Gunter, Marc J. A1 - Maria Huerta, Jose A1 - Kaaks, Rudolf A1 - Key, Timothy J. A1 - Khaw, Kay Tee A1 - Krogh, Vittorio A1 - Kuehn, Tilman A1 - Mancini, Francesca Romana A1 - Mattiello, Amalia A1 - Nilsson, Peter M. A1 - Olsen, Anja A1 - Overvad, Kim A1 - Palli, Domenico A1 - Ramon Quiros, J. A1 - Rolandsson, Olov A1 - Sacerdote, Carlotta A1 - Sala, Nuria A1 - Salamanca-Fernandez, Elena A1 - Sluijs, Ivonne A1 - Spijkerman, Annemieke M. W. A1 - Tjonneland, Anne A1 - Tsilidis, Konstantinos K. A1 - Tumino, Rosario A1 - van der Schouw, Yvonne T. A1 - Forouhi, Nita G. A1 - Sharp, Stephen J. A1 - Langenberg, Claudia A1 - Riboli, Elio A1 - Schulze, Matthias Bernd A1 - Wareham, Nicholas J. T1 - Circulating Fetuin-A and Risk of Type 2 Diabetes BT - a mendelian randomization analysis JF - Diabetes : a journal of the American Diabetes Association N2 - Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population. Y1 - 2018 U6 - https://doi.org/10.2337/db17-1268 SN - 0012-1797 SN - 1939-327X VL - 67 IS - 6 SP - 1200 EP - 1205 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Rothwell, Joseph A. A1 - Murphy, Neil A1 - Aleksandrova, Krasimira A1 - Schulze, Matthias Bernd A1 - Bešević, Jelena A1 - Kliemann, Nathalie A1 - Jenab, Mazda A1 - Ferrari, Pietro A1 - Achaintre, David A1 - Gicquiau, Audrey A1 - Vozar, Béatrice A1 - Scalbert, Augustin A1 - Huybrechts, Inge A1 - Freisling, Heinz A1 - Prehn, Cornelia A1 - Adamski, Jerzy A1 - Cross, Amanda J. A1 - Pala, Valeria Maria A1 - Boutron-Ruault, Marie-Christine A1 - Dahm, Christina C. A1 - Overvad, Kim A1 - Gram, Inger Torhild A1 - Sandanger, Torkjel M. A1 - Skeie, Guri A1 - Jakszyn, Paula A1 - Tsilidis, Kostas K. A1 - Hughes, David J. A1 - van Guelpen, Bethany A1 - Bodén, Stina A1 - Sánchez, Maria-José A1 - Schmidt, Julie A. A1 - Katzke, Verena A1 - Kühn, Tilman A1 - Colorado-Yohar, Sandra A1 - Tumino, Rosario A1 - Bueno-de-Mesquita, Bas A1 - Vineis, Paolo A1 - Masala, Giovanna A1 - Panico, Salvatore A1 - Eriksen, Anne Kirstine A1 - Tjønneland, Anne A1 - Aune, Dagfinn A1 - Weiderpass, Elisabete A1 - Severi, Gianluca A1 - Chajès, Véronique A1 - Gunter, Marc J. T1 - Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort JF - Clinical gastroenterology and hepatology N2 - BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer. KW - colorectal neoplasm KW - risk factors KW - World Cancer Research Fund/American Institute for Cancer Research Recommendations KW - targeted metabolomics Y1 - 2020 U6 - https://doi.org/10.1016/j.cgh.2020.11.045 SN - 1542-3565 SN - 1542-7714 VL - 20 SP - E1061 EP - E1082 PB - Elsevier CY - New York, NY ER - TY - JOUR A1 - Zheng, Ju-Sheng A1 - Luan, Jian'an A1 - Sofianopoulou, Eleni A1 - Imamura, Fumiaki A1 - Stewart, Isobel D. A1 - Day, Felix R. A1 - Pietzner, Maik A1 - Wheeler, Eleanor A1 - Lotta, Luca A. A1 - Gundersen, Thomas E. A1 - Amiano, Pilar A1 - Ardanaz, Eva A1 - Chirlaque, Maria-Dolores A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Kaaks, Rudolf A1 - Laouali, Nasser A1 - Mancini, Francesca Romana A1 - Nilsson, Peter M. A1 - Onland-Moret, N. Charlotte A1 - Olsen, Anja A1 - Overvad, Kim A1 - Panico, Salvatore A1 - Palli, Domenico A1 - Ricceri, Fulvio A1 - Rolandsson, Olov A1 - Spijkerman, Annemieke M. W. A1 - Sanchez, Maria-Jose A1 - Schulze, Matthias Bernd A1 - Sala, Nuria A1 - Sieri, Sabina A1 - Tjonneland, Anne A1 - Tumino, Rosario A1 - van der Schouw, Yvonne T. A1 - Weiderpass, Elisabete A1 - Riboli, Elio A1 - Danesh, John A1 - Butterworth, Adam S. A1 - Sharp, Stephen J. A1 - Langenberg, Claudia A1 - Forouhi, Nita G. A1 - Wareham, Nicholas J. T1 - Plasma vitamin C and type 2 diabetes BT - genome-wide association study and Mendelian randomization analysis in European populations JF - Diabetes care N2 - OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 x 10(-8)), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention. Y1 - 2020 U6 - https://doi.org/10.2337/dc20-1328 SN - 0149-5992 SN - 1935-5548 VL - 44 IS - 1 SP - 98 EP - 106 PB - American Diabetes Association CY - Alexandria ER -