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1. Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies

Author

Rodríguez-Carrillo, Andrea, Salamanca-Fernández, Elena, den Hond, Elly, Verheyen, Veerle J., Fábelová, Lucia, Murinova, Lubica Palkovicova, Pedraza-Díaz, Susana, Castaño, Argelia, García-Lario, José Vicente, Remy, Sylvie, Govarts, Eva, Schoeters, Greet, Olea, Nicolás, Freire, Carmen, and Fernández, Mariana F.

Published
2023
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4. Implementation of effect biomarkers in human biomonitoring studies: A systematic approach synergizing toxicological and epidemiological knowledge

Author

Rodríguez-Carrillo, Andrea, Mustieles, Vicente, Salamanca-Fernández, Elena, Olivas-Martínez, Alicia, Suárez, Beatriz, Bajard, Lola, Baken, Kirsten, Blaha, Ludek, Bonefeld-Jørgensen, Eva Cecilie, Couderq, Stephan, D'Cruz, Shereen Cynthia, Fini, Jean-Baptiste, Govarts, Eva, Gundacker, Claudia, Hernández, Antonio F., Lacasaña, Marina, Laguzzi, Federica, Linderman, Birgitte, Long, Manhai, Louro, Henriqueta, Neophytou, Christiana, Oberemn, Axel, Remy, Sylvie, Rosenmai, Anna Kjerstine, Saber, Anne Thoustrup, Schoeters, Greet, Silva, Maria Joao, Smagulova, Fatima, Uhl, Maria, Vinggaard, Anne Marie, Vogel, Ulla, Wielsøe, Maria, Olea, Nicolás, and Fernández, Mariana F.

Published
2023
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6. Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES

Author

Luque-Fernández, Miguel Ángel, Redondo-Sánchez, Daniel, Fernández, Pablo, Salamanca-Fernández, Elena, Marcos-Gragera, Rafael, Guevara, Marcela, Carulla Aresté, Marià, Jiménez, Rosario, Núñez, Olivier, Sabater, Consol, López de Munain Marqués, Arantxa, Chirlaque, María Dolores, Mateos, Antonio, Rodríguez-Barranco, Miguel, Espín Balbino, Jaime, Pollán, Marina, and Sánchez, María-José

Published
2021
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11. Bisphenol-A in the European Prospective Investigation into Cancer and Nutrition cohort in Spain: Levels at recruitment and associated dietary factors

Author

Salamanca-Fernández, Elena, Rodríguez-Barranco, Miguel, Arrebola, Juan Pedro, Vela, Fernando, Díaz, Caridad, Chirlaque, María Dolores, Colorado-Yohar, Sandra, Jiménez-Zabala, Ana, Irizar, Amaia, Guevara, Marcela, Ardanaz, Eva, Iribarne-Durán, Luz María, Pérez del Palacio, José, Olea, Nicolás, Agudo, Antonio, and Sánchez, Maria-José

Published
2020
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12. Estimated Substitution of Tea or Coffee for Sugar-Sweetened Beverages Was Associated with Lower Type 2 Diabetes Incidence in Case–Cohort Analysis across 8 European Countries in the EPIC-InterAct Study

Author

Imamura, Fumiaki, Schulze, Matthias B, Sharp, Stephen J, Guevara, Marcela, Romaguera, Dora, Bendinelli, Benedetta, Salamanca-Fernández, Elena, Ardanaz, Eva, Arriola, Larraitz, Aune, Dagfinn, Boeing, Heiner, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Freisling, Heinz, Jakszyn, Paula, Kaaks, Rudolf, Khaw, Kay-Tee, Kühn, Tilman, Mancini, Francesca R, Masala, Giovanna, Chirlaque, Maria-Dolores, Nilsson, Peter M, Overvad, Kim, Pala, Valeria M, Panico, Salvatore, Perez-Cornago, Aurora, Quirós, Jose R, Ricceri, Fulvio, Rodríguez-Barranco, Miguel, Rolandsson, Olov, Sluijs, Ivonne, Stepien, Magdalena, Spijkerman, Annemieke M W, Tjønneland, Anne, Tong, Tammy Y N, Tumino, Rosario, Vissers, Linda E T, Ward, Heather A, Langenberg, Claudia, Riboli, Elio, Forouhi, Nita G, and Wareham, Nick J

Published
2019
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14. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author

Wood, Angela M, Kaptoge, Stephen, Butterworth, Adam, Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S, Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi M, Verschuren, Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Veikko, Salomaa, Nordestgaard, Børge G, Yeap, Bu B, Flecther, Astrid, Melander, Olle, Kuller, Lewis H, Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Arndt, Volker, Franco, Oscar H, Wennberg, Patrik, Gallacher, John, Gómez de la Cámara, Agustín, Völzke, Henry, Dahm, Christina C, Dale, Caroline E, Bergmann, Manuela, Crespo, Carlos, van der Schouw, Yvonne T, Kaaks, Rudolf, Simons, Leon A, Lagiou, Pagona, Schoufour, Josje D, Boer, Jolanda M.A, Key, Timothy J, Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W, Taylor, James O, Sacerdote, Carlotta, Wallace, Robert B, Quiros, J. Ramon, Rimm, Eric B, Tumino, Rosario, Blazer III, Dan G, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Salomaa, Veikko, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J, Psaty, Bruce M, Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M, Grioni, Sara, Palli, Domenico, Huerta, José M, Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C, Panagiotakos, Demosthenes B, Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E, Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J, Sakurai, Masaru, Shaw, Jonathan E, Knuiman, Matthew, Voortman, Trudy, Meisinger, Christa, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean-Pierre, Brunner, Eric J, Assmann, Gerd, Trevisan, Maurizio, Gillumn, Richard F, Ford, Ian Ford, Sattar, Naveed, Lazo, Mariana, Thompson, Simon, Ferrari, Pietro, Leon, David A, Davey Smith, George, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Butterworth, Adam S, Verschuren, W M Monique, Fletcher, Astrid, de la Cámara, Agustín Gómez, Bergmann, Manuela M, Crespo, Carlos J, Boer, Jolanda M A, Quiros, J Ramon, Blazer, Dan G, II, Dallongeville, Jean, Gillum, Richard F, Ford, Ian, Thompson, Simon G, and Smith, George Davey

Published
2018
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15. Consumption of Fish Is Not Associated with Risk of Differentiated Thyroid Carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Author

Zamora-Ros, Raul, Castañeda, Jazmín, Rinaldi, Sabina, Cayssials, Valerie, Slimani, Nadia, Weiderpass, Elisabete, Tsilidis, Konstantinos K, Boutron-Ruault, Marie-Christine, Overvad, Kim, Eriksen, Anne K, Tjønneland, Anne, Kühn, Tilman, Katzke, Verena, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Palli, Domenico, Grioni, Sara, Mattiello, Amalia, Tumino, Rosario, Sciannameo, Veronica, Lund, Eiliv, Merino, Susana, Salamanca-Fernández, Elena, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Ericson, Ulrika, Almquist, Martin, Hennings, Joakim, Sandström, Maria, Bueno-de-Mesquita, H Bas, Peeters, Petra H, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Cross, Amanda J, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Agudo, Antonio, and Franceschi, Silvia

Published
2017
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17. Greenhouse gases emissions from the diet and risk of death and chronic diseases in the EPIC-Spain cohort

Author

González, Carlos A, primary, Bonet, Catalina, additional, de Pablo, Miguel, additional, Sanchez, María José, additional, Salamanca-Fernandez, Elena, additional, Dorronsoro, Miren, additional, Amiano, Pilar, additional, Huerta, Jose María, additional, Chirlaque, María Dolores, additional, Ardanaz, Eva, additional, Barricarte, Aurelio, additional, Quirós, Jose Ramón, additional, Agudo, Antonio, additional, and Rivera Ferrer, Marta Guadalupe, additional

Published
2020
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19. Circulating Fetuin-A and Risk of Type 2 Diabetes

Author

Kroeger, Janine, Meidtner, Karina, Stefan, Norbert, Guevara, Marcela, Kerrison, Nicola D., Ardanaz, Eva, Aune, Dagfinn, Boeing, Heiner (apl. Prof. Dr.), Dorronsoro, Miren, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W., Freisling, Heinz, Gunter, Marc J., Maria Huerta, Jose, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay Tee, Krogh, Vittorio, Kuehn, Tilman, Mancini, Francesca Romana, Mattiello, Amalia, Nilsson, Peter M., Olsen, Anja, Overvad, Kim, Palli, Domenico, Ramon Quiros, J., Rolandsson, Olov, Sacerdote, Carlotta, Sala, Nuria, Salamanca-Fernandez, Elena, Sluijs, Ivonne, Spijkerman, Annemieke M. W., Tjonneland, Anne, Tsilidis, Konstantinos K., Tumino, Rosario, van der Schouw, Yvonne T., Forouhi, Nita G., Sharp, Stephen J., Langenberg, Claudia, Riboli, Elio, Schulze, Matthias B. (Prof. Dr.), and Wareham, Nicholas J.

Subjects
ddc:570, Institut für Biochemie und Biologie
Abstract

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.

Published
2018

20. Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma : results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Zamora-Ros, Raul, Alghamdi, Muath A., Cayssials, Valerie, Franceschi, Silvia, Almquist, Martin, Hennings, Joakim, Sandström, Maria, 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, Zamora-Ros, Raul, Alghamdi, Muath A., Cayssials, Valerie, Franceschi, Silvia, Almquist, Martin, Hennings, Joakim, Sandström, Maria, 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, and Rinaldi, Sabina

Abstract

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.

Published
2019
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21. Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes : EPIC-InterAct Case-Cohort Study

Author

Zheng, Ju-Sheng, 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, 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., Zheng, Ju-Sheng, 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, 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., and Wareham, Nicholas J.

Abstract

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.

Published
2019
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22. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author

Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyro, Cecilie, Olsen, Anja, Affret, Aurelie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kuehn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Buen-de-Mesquita, Bas, Peeters, Petra H., Hjartaker, Anette, Rylander, Charlotta, Skeie, Guri, Ramon Quiros, J., Jakszyn, Paula, Salamanca-Fernandez, Elena, Maria Huerta, Jose, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, and Deschasaux, Mélanie

Subjects
cardiovascular-disease risk, front-of-package, dietary index, prospective association, su.vi.max cohort, french adults, validation, database, project, france
Abstract

Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

Published
2018

23. Greenhouse gases emissions from the diet and risk of death and chronic diseases in the EPIC-Spain cohort.

Author

González, Carlos A, Bonet, Catalina, Pablo, Miguel de, Sanchez, María José, Salamanca-Fernandez, Elena, Dorronsoro, Miren, Amiano, Pilar, Huerta, Jose María, Chirlaque, María Dolores, Ardanaz, Eva, Barricarte, Aurelio, Quirós, Jose Ramón, Agudo, Antonio, and Ferrer, Marta Guadalupe Rivera

Subjects
CHRONIC disease risk factors, MORTALITY risk factors, AGE distribution, CARBON dioxide, CONFIDENCE intervals, CORONARY disease, DIET, GREENHOUSE gases, INGESTION, MEAT, TYPE 2 diabetes, EDUCATIONAL attainment, DESCRIPTIVE statistics
Abstract

Background Evidence from the scientific literature shows a significant variation in greenhouse gas (GHG) emissions from the diet, according to the type of food consumed. We aim to analyze the relationship between the daily dietary GHG emissions according to red meat, fruit and vegetables consumption and their relationship with risk of total mortality, and incident risk of chronic diseases. Methods We examined data on the EPIC-Spain prospective study, with a sample of 40 621 participants. Dietary GHG emission values were calculated for 57 food items of the EPIC study using mean emission data from a systematic review of 369 published studies. Results Dietary GHG emissions (kgCO2eq/day), per 2000 kcal, were 4.7 times higher in those with high red-meat consumption (>140 g/day) than those with low consumption (<70 g/day). The average dietary GHG emissions were similar in males and females, but it was significantly higher in youngest people and in those individuals with lower educational level, as well as for northern EPIC centers of Spain. We found a significant association with the risk of mortality comparing the third vs. the first tertile of dietary GHG emissions [hazard ratio (HR) 1.095; 95% confidence interval (CI) 1.007–1.19; trend test 0.037]. Risk of coronary heart disease (HR 1.26; 95% CI 1.08–1.48; trend test 0.003) and risk of type 2 diabetes (HR 1.24; 95% CI 1.11–1.38; trend test 0.002) showed significant association as well. Conclusions Decreasing red-meat consumption would lead to reduce GHG emissions from diet and would reduce risk of mortality, coronary heart disease and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Published
2021
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24. Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author

Wood, Angela M., Kaptoge, Stephen, Butterworth, Adam S., Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S., Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi M., Verschuren, W. M. Monique, Sato, Shinichi, Njolstad, Inger, Woodward, Mark, Salomaa, Veikko, Nordestgaard, Borge G., Yeap, Bu B., Fletcher, Astrid, Melander, Olle, Kuller, Lewis H., Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Arndt, Volker, Franco, Oscar H., Wennberg, Patrik, Gallacher, John, de la Camara, Agustin Gomez, Volzke, Henry, Dahm, Christina C., Dale, Caroline E., Bergmann, Manuela M., Crespo, Carlos J., van der Schouw, Yvonne T., Kaaks, Rudolf, Simons, Leon A., Lagiou, Pagona, Schoufour, Josje D., Boer, Jolanda M. A., Key, Timothy J., Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W., Taylor, James O., Sacerdote, Carlotta, Wallace, Robert B., Quiros, J. Ramon, Tumino, Rosario, Blazer, Dan G., II, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J., Psaty, Bruce M., Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M., Grioni, Sara, Palli, Domenico, Huerta, Jose M., Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C., Panagiotakos, Demosthenes B., Karakatsani, Anna, Trichopoulou, Antonia, Kuhn, Tilman, Grobbee, Diederick E., Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Despres, Jean-Pierre, Cushman, Mary, Cooper, Jackie A., Rodriguez, Carlos J., Sakurai, Masaru, Shaw, Jonathan E., Knuiman, Matthew, Voortman, Trudy, Meisinger, Christa, Tjonneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J., Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F., Ford, Ian, Sattar, Naveed, Lazo, Mariana, Thompson, Simon G., Ferrari, Pietro, Leon, David A., Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Wood, Angela M., Kaptoge, Stephen, Butterworth, Adam S., Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S., Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi M., Verschuren, W. M. Monique, Sato, Shinichi, Njolstad, Inger, Woodward, Mark, Salomaa, Veikko, Nordestgaard, Borge G., Yeap, Bu B., Fletcher, Astrid, Melander, Olle, Kuller, Lewis H., Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Arndt, Volker, Franco, Oscar H., Wennberg, Patrik, Gallacher, John, de la Camara, Agustin Gomez, Volzke, Henry, Dahm, Christina C., Dale, Caroline E., Bergmann, Manuela M., Crespo, Carlos J., van der Schouw, Yvonne T., Kaaks, Rudolf, Simons, Leon A., Lagiou, Pagona, Schoufour, Josje D., Boer, Jolanda M. A., Key, Timothy J., Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W., Taylor, James O., Sacerdote, Carlotta, Wallace, Robert B., Quiros, J. Ramon, Tumino, Rosario, Blazer, Dan G., II, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J., Psaty, Bruce M., Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M., Grioni, Sara, Palli, Domenico, Huerta, Jose M., Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C., Panagiotakos, Demosthenes B., Karakatsani, Anna, Trichopoulou, Antonia, Kuhn, Tilman, Grobbee, Diederick E., Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Despres, Jean-Pierre, Cushman, Mary, Cooper, Jackie A., Rodriguez, Carlos J., Sakurai, Masaru, Shaw, Jonathan E., Knuiman, Matthew, Voortman, Trudy, Meisinger, Christa, Tjonneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J., Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F., Ford, Ian, Sattar, Naveed, Lazo, Mariana, Thompson, Simon G., Ferrari, Pietro, Leon, David A., Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, and Danesh, John

Abstract

Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies. Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around

Published
2018
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25. Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author

Lin, Crystal, Travis, Ruth C., Appleby, Paul N., Tipper, Sarah, Weiderpass, Elisabete, Chang-Claude, Jenny, Gram, Inger T., Kaaks, Rudolf, Kiemeney, Lambertus A., Ljungberg, Börje, Tumino, Rosario, Tjonneland, Anne, Roswall, Nina, Overvad, Kim, Boutron-Ruault, Marie-Christine, Manciniveri, Francesca Romana, Severi, Gianluca, Trichopoulou, Antonia, Masala, Giovanna, Sacerdote, Carlotta, Agnoli, Claudia, Panico, Salvatore, Bueno-de-Mesquita, Bas, Peeters, Petra H., Salamanca-Fernandez, Elena, Chirlaque, Maria-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Menendez, Virginia, Lujan-Barroso, Leila, Liedberg, Fredrik, Freisling, Heinz, Gunter, Marc, Aune, Dagfinn, Cross, Amanda J., Riboli, Elio, Key, Timothy J., Perez-Cornago, Aurora, Lin, Crystal, Travis, Ruth C., Appleby, Paul N., Tipper, Sarah, Weiderpass, Elisabete, Chang-Claude, Jenny, Gram, Inger T., Kaaks, Rudolf, Kiemeney, Lambertus A., Ljungberg, Börje, Tumino, Rosario, Tjonneland, Anne, Roswall, Nina, Overvad, Kim, Boutron-Ruault, Marie-Christine, Manciniveri, Francesca Romana, Severi, Gianluca, Trichopoulou, Antonia, Masala, Giovanna, Sacerdote, Carlotta, Agnoli, Claudia, Panico, Salvatore, Bueno-de-Mesquita, Bas, Peeters, Petra H., Salamanca-Fernandez, Elena, Chirlaque, Maria-Dolores, Ardanaz, Eva, Dorronsoro, Miren, Menendez, Virginia, Lujan-Barroso, Leila, Liedberg, Fredrik, Freisling, Heinz, Gunter, Marc, Aune, Dagfinn, Cross, Amanda J., Riboli, Elio, Key, Timothy J., and Perez-Cornago, Aurora

Abstract

Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk.

Published
2018
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26. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe : results from the EPIC prospective cohort study

Author

Deschasaux, Melanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyro, Cecilie, Olsen, Anja, Affret, Aurelie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kuehn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Buen-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramon Quiros, J., Jakszyn, Paula, Salamanca-Fernandez, Elena, Maria Huerta, Jose, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, Deschasaux, Melanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyro, Cecilie, Olsen, Anja, Affret, Aurelie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kuehn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Buen-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramon Quiros, J., Jakszyn, Paula, Salamanca-Fernandez, Elena, Maria Huerta, Jose, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., and Touvier, Mathilde

Abstract

Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P

Published
2018
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27. Circulating Fetuin-A and Risk of Type 2 Diabetes : A Mendelian Randomization Analysis

Author

Kroeger, Janine, Meidtner, Karina, Stefan, Norbert, Guevara, Marcela, Kerrison, Nicola D., Ardanaz, Eva, Aune, Dagfinn, Boeing, Heiner, Dorronsoro, Miren, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W., Freisling, Heinz, Gunter, Marc J., Huerta, José Maria, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay Tee, Krogh, Vittorio, Kuehn, Tilman, Mancini, Francesca Romana, Mattiello, Amalia, Nilsson, Peter M., Olsen, Anja, Overvad, Kim, Palli, Domenico, Quiros, J. Ramon, Rolandsson, Olov, Sacerdote, Carlotta, Sala, Nuria, Salamanca-Fernandez, Elena, Sluijs, Ivonne, Spijkerman, Annemieke M. W., Tjonneland, Anne, Tsilidis, Konstantinos K., Tumino, Rosario, van der Schouw, Yvonne T., Forouhi, Nita G., Sharp, Stephen J., Langenberg, Claudia, Riboli, Elio, Schulze, Matthias B., Wareham, Nicholas J., Kroeger, Janine, Meidtner, Karina, Stefan, Norbert, Guevara, Marcela, Kerrison, Nicola D., Ardanaz, Eva, Aune, Dagfinn, Boeing, Heiner, Dorronsoro, Miren, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W., Freisling, Heinz, Gunter, Marc J., Huerta, José Maria, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay Tee, Krogh, Vittorio, Kuehn, Tilman, Mancini, Francesca Romana, Mattiello, Amalia, Nilsson, Peter M., Olsen, Anja, Overvad, Kim, Palli, Domenico, Quiros, J. Ramon, Rolandsson, Olov, Sacerdote, Carlotta, Sala, Nuria, Salamanca-Fernandez, Elena, Sluijs, Ivonne, Spijkerman, Annemieke M. W., Tjonneland, Anne, Tsilidis, Konstantinos K., Tumino, Rosario, van der Schouw, Yvonne T., Forouhi, Nita G., Sharp, Stephen J., Langenberg, Claudia, Riboli, Elio, Schulze, Matthias B., and Wareham, Nicholas J.

Abstract

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.

Published
2018
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28. Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Zamora-Ros, Raul, Beraud, Virginie, Franceschi, Silvia, Cayssials, Valerie, Tsilidis, Konstantinos K., Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Overvad, Kim, Tjonneland, Anne, Eriksen, Anne K., Bonnet, Fabrice, Affret, Aurelie, Katzke, Verena, Kuehn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, Valanou, Elisavet, Karakatsani, Anna, Masala, Giovanna, Grioni, Sara, de Magistris, Maria Santucci, Tumino, Rosario, Ricceri, Fulvio, Skeie, Guri, Parr, Christine L., Merino, Susana, Salamanca-Fernandez, Elena, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Almquist, Martin, Drake, Isabel, Hennings, Joakim, Sandström, Maria, Bueno-de-Mesquita, H. B(as), Peeters, Petra H., Khaw, Kay-Thee, Wareham, Nicholas J., Schmidt, Julie A., Perez-Cornago, Aurora, Aune, Dagfinn, Riboli, Elio, Slimani, Nadia, Scalbert, Augustin, Romieu, Isabelle, Agudo, Antonio, Rinaldi, Sabina, Zamora-Ros, Raul, Beraud, Virginie, Franceschi, Silvia, Cayssials, Valerie, Tsilidis, Konstantinos K., Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Overvad, Kim, Tjonneland, Anne, Eriksen, Anne K., Bonnet, Fabrice, Affret, Aurelie, Katzke, Verena, Kuehn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, Valanou, Elisavet, Karakatsani, Anna, Masala, Giovanna, Grioni, Sara, de Magistris, Maria Santucci, Tumino, Rosario, Ricceri, Fulvio, Skeie, Guri, Parr, Christine L., Merino, Susana, Salamanca-Fernandez, Elena, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Almquist, Martin, Drake, Isabel, Hennings, Joakim, Sandström, Maria, Bueno-de-Mesquita, H. B(as), Peeters, Petra H., Khaw, Kay-Thee, Wareham, Nicholas J., Schmidt, Julie A., Perez-Cornago, Aurora, Aune, Dagfinn, Riboli, Elio, Slimani, Nadia, Scalbert, Augustin, Romieu, Isabelle, Agudo, Antonio, and Rinaldi, Sabina

Abstract

Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend=0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend=0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend=0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend=0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.

Published
2018
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29. The influence of lifestyle, diet, and reproductive history on age at natural menopause in Spain: analysis from the EPIC-Spain sub-cohort

Author

Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. KEMLG - Grup d'Enginyeria del Coneixement i Aprenentatge Automàtic, Luján-Barroso, Leila, Gibert, Karina, Obón-Santacana, Mireia, Chirlaque, Maria Dolores, Sánchez, Maria-José, Larrañaga, Nerea, Barricarte, Aurelio, Quirós, Jose-Ramón, Salamanca-Fernandez, Elena, Colorado-Yohar, Sandra, Gomez-Pozo, Basilio, Agudo, Antonio, Duell, Eric J, Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. KEMLG - Grup d'Enginyeria del Coneixement i Aprenentatge Automàtic, Luján-Barroso, Leila, Gibert, Karina, Obón-Santacana, Mireia, Chirlaque, Maria Dolores, Sánchez, Maria-José, Larrañaga, Nerea, Barricarte, Aurelio, Quirós, Jose-Ramón, Salamanca-Fernandez, Elena, Colorado-Yohar, Sandra, Gomez-Pozo, Basilio, Agudo, Antonio, and Duell, Eric J

Abstract

This is the peer reviewed version of the following article: Luján-Barroso, L. [et al.]. The influence of lifestyle, diet, and reproductive history on age at natural menopause in Spain: analysis from the EPIC-Spain sub-cohort. "American Journal of Human Biology", Novembre 2018, vol. 30, núm. 6, article e23181., which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1002/ajhb.23181. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited., Objective To determinate the role of lifestyle factors, recent diet, menstrual factors, and reproductive history in age at natural menopause in adult Spanish women. Methods In total, 12¿562 pre-menopausal women were available for analysis from the EPIC-Spain sub-cohort. Women were recruited between 1992 and 1996 in five regions of Spain (Asturias, Granada, Murcia, Navarra, and San Sebastian) and, for these analyses, were followed for 3 years. Questionnaires on diet, lifestyle, anthropometric measurements, and reproductive and exogenous hormones history were collected at baseline. Menopause status was updated at a median of 3 years of follow-up. Results After a median of 3 years of follow-up 1166 women became postmenopausal. An earlier age at menopause was observed in current smokers (HR: 1.29; 95%CI 1.08-1.55) and in non-users of oral contraceptives (HR: 1.32; 95%CI 1.01-1.57). A later age at menopause was observed in women with irregular menses (HR: 0.71; 95%CI 0.56-0.91) and in women with a higher number of pregnancies (HR: 0.74; 95%CI 0.56-0.94). Conclusions Our results confirm that women who smoked had an earlier age at natural menopause, while use of oral contraceptives, higher number of pregnancies, and irregularity of menses were associated with a prolonged reproductive lifespan. No associations were observed for dietary habits assessed after the age of 40¿years., Peer Reviewed, Objectius de Desenvolupament Sostenible::3 - Salut i Benestar, Postprint (author's final draft)

Published
2018

30. Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition

Author

Caini, Saverio Masala, Giovanna Saieva, Calogero Kvaskoff, Marina Savoye, Isabelle Sacerdote, Carlotta Hemmingsson, Oskar Bech, Bodil Hammer Overvad, Kim Tjonneland, Anne and Petersen, Kristina E. N. Mancini, Francesca Romana and Boutron-Ruault, Marie-Christine Cervenka, Iris Kaaks, Rudolf and Kuehn, Tilman Boeing, Heiner Floegel, Anna Trichopoulou, Antonia Valanou, Elisavet Kritikou, Maria Tagliabue, Giovanna Panico, Salvatore Tumino, Rosario and Bueno-de-Mesquita, H. B(as) Peeters, Petra H. Veierod, Marit B. and Ghiasvand, Reza Lukic, Marko Ramon Quiros, Jose and Chirlaque, Maria-Dolores Ardanaz, Eva Salamanca Fernandez, Elena and Larranaga, Nerea Zamora-Ros, Raul Nilsson, Lena Maria and Ljuslinder, Ingrid Jirstrom, Karin Sonestedt, Emily Key, Timothy J. Wareham, Nick Khaw, Kay-Tee Gunter, Marc and Huybrechts, Inge Murphy, Neil Tsilidis, Konstantinos K. and Weiderpass, Elisabete Palli, Domenico

Abstract

What’s new? Laboratory studies suggest that coffee and tea protect against melanoma, but epidemiological findings are inconsistent. Here the authors studied more than 400,000 participants within the European Prospective Investigation into Cancer and Nutrition (EPIC) and confirmed an inverse association between caffeinated coffee consumption and melanoma risk. No association was found with decaffeinated coffee or tea. Interestingly, drinking coffee only protected men, but not women, from developing the often fatal skin cancer, raising interesting questions about gender-specific hormones or coffee habits influencing this association. In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.

Published
2017

31. Coffee, tea and melanoma risk : findings from the European Prospective Investigation into Cancer and Nutrition

Author

Caini, Saverio, Masala, Giovanna, Saieva, Calogero, Kvaskoff, Marina, Sacerdote, Carlotta, Savoye, Isabelle, Hemmingsson, Oskar, Bech, Bodil Hammer, Overvad, Kim, Tjonneland, Anne, Petersen, Kristina E. N., Mancini, Francesca Romana, Boutron-Ruault, Marie-Christine, Cervenka, Iris, Kaaks, Rudolf, Kuehn, Tilman, Boeing, Heiner, Floegel, Anna, Trichopoulou, Antonia, Valanou, Elisavet, Kritikou, Maria, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Bueno-de-Mesquita, H. B(as), Peeters, Petra H., Veierod, Marit B., Ghiasvand, Reza, Lukic, Marko, Ramon Quiros, Jose, Chirlaque, Maria-Dolores, Ardanaz, Eva, Salamanca Fernandez, Elena, Larranaga, Nerea, Zamora-Ros, Raul, Nilsson, Lena Maria, Ljuslinder, Ingrid, Jirstrom, Karin, Sonestedt, Emily, Key, Timothy J., Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc, Huybrechts, Inge, Murphy, Neil, Tsilidis, Konstantinos K., Weiderpass, Elisabete, Palli, Domenico, Caini, Saverio, Masala, Giovanna, Saieva, Calogero, Kvaskoff, Marina, Sacerdote, Carlotta, Savoye, Isabelle, Hemmingsson, Oskar, Bech, Bodil Hammer, Overvad, Kim, Tjonneland, Anne, Petersen, Kristina E. N., Mancini, Francesca Romana, Boutron-Ruault, Marie-Christine, Cervenka, Iris, Kaaks, Rudolf, Kuehn, Tilman, Boeing, Heiner, Floegel, Anna, Trichopoulou, Antonia, Valanou, Elisavet, Kritikou, Maria, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Bueno-de-Mesquita, H. B(as), Peeters, Petra H., Veierod, Marit B., Ghiasvand, Reza, Lukic, Marko, Ramon Quiros, Jose, Chirlaque, Maria-Dolores, Ardanaz, Eva, Salamanca Fernandez, Elena, Larranaga, Nerea, Zamora-Ros, Raul, Nilsson, Lena Maria, Ljuslinder, Ingrid, Jirstrom, Karin, Sonestedt, Emily, Key, Timothy J., Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc, Huybrechts, Inge, Murphy, Neil, Tsilidis, Konstantinos K., Weiderpass, Elisabete, and Palli, Domenico

Abstract

What's new? Laboratory studies suggest that coffee and tea protect against melanoma, but epidemiological findings are inconsistent. Here the authors studied more than 400,000 participants within the European Prospective Investigation into Cancer and Nutrition (EPIC) and confirmed an inverse association between caffeinated coffee consumption and melanoma risk. No association was found with decaffeinated coffee or tea. Interestingly, drinking coffee only protected men, but not women, from developing the often fatal skin cancer, raising interesting questions about gender-specific hormones or coffee habits influencing this association. In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. Th

Published
2017
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32. Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes A Meta-analysis

Author

Lotta, Luca A., Sharp, Stephen J., Burgess, Stephen, Perry, John R. B., Stewart, Isobel D., Willems, Sara M., Luan, Jian'an, Ardanaz, Eva, Arriola, Larraitz, Balkau, Beverley, Boeing, Heiner, Deloukas, Panos, Forouhi, Nita G., Franks, Paul W., Grioni, Sara, Kaaks, Rudolf, Key, Timothy J., Navarro, Carmen, Nilsson, Peter M., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quiros, Jose-Ramon, Riboli, Elio, Rolandsson, Olov, Sacerdote, Carlotta, Salamanca-Fernandez, Elena, Slimani, Nadia, Spijkerman, Annemieke M. W., Tjonneland, Anne, Tumino, Rosario, van der A, Daphne L., van der Schouw, Yvonne T., McCarthy, Mark I., Barroso, Ines, O'Rahilly, Stephen, Savage, David B., Sattar, Naveed, Langenberg, Claudia, Scott, Robert A., Wareham, Nicholas J., Lotta, Luca A., Sharp, Stephen J., Burgess, Stephen, Perry, John R. B., Stewart, Isobel D., Willems, Sara M., Luan, Jian'an, Ardanaz, Eva, Arriola, Larraitz, Balkau, Beverley, Boeing, Heiner, Deloukas, Panos, Forouhi, Nita G., Franks, Paul W., Grioni, Sara, Kaaks, Rudolf, Key, Timothy J., Navarro, Carmen, Nilsson, Peter M., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quiros, Jose-Ramon, Riboli, Elio, Rolandsson, Olov, Sacerdote, Carlotta, Salamanca-Fernandez, Elena, Slimani, Nadia, Spijkerman, Annemieke M. W., Tjonneland, Anne, Tumino, Rosario, van der A, Daphne L., van der Schouw, Yvonne T., McCarthy, Mark I., Barroso, Ines, O'Rahilly, Stephen, Savage, David B., Sattar, Naveed, Langenberg, Claudia, Scott, Robert A., and Wareham, Nicholas J.

Abstract

Importance Low-density lipoprotein cholesterol (LDL-C)–lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes. Objective To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes. Design, Setting, and Participants The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016. Exposures Low-density lipoprotein cholesterol–lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR. Main Outcomes and Measures Odds ratios (ORs) for type 2 diabetes and coronary artery disease. Results Low-density lipoprotein cholesterol–lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95% CI, 1.70-3.43]; P < .001). For PCSK9 genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95% CI, 1.02-1.38; P = .03). For a

Published
2016
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33. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: A meta-analysis

Author

Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lotta, Luca A., Sharp, Stephen J., Burgess, Stephen, Perry, John R B, Stewart, Isobel D., Willems, Sara M., Luan, Jian'an, Ardanaz, Eva, Arriola, Larraitz, Balkau, Beverley, Boeing, Heiner, Deloukas, Panos, Forouhi, Nita G., Franks, Paul W., Grioni, Sara, Kaaks, Rudolf, Key, Timothy J., Navarro, Carmen, Nilsson, Peter M., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, Jose Ramón, Riboli, Elio, Rolandsson, Olov, Sacerdote, Carlotta, Salamanca-Fernandez, Elena, Slimani, Nadia, Spijkerman, Annemieke M W, Tjonneland, Anne, Tumino, Rosario, Van Der A, Daphne L., Van Der Schouw, Yvonne T., McCarthy, Mark I., Barroso, Inês, O'Rahilly, Stephen, Savage, David B., Sattar, Naveed, Langenberg, Claudia, Scott, Robert A., Wareham, Nicholas J., Cardiovasculaire Epidemiologie, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Lotta, Luca A., Sharp, Stephen J., Burgess, Stephen, Perry, John R B, Stewart, Isobel D., Willems, Sara M., Luan, Jian'an, Ardanaz, Eva, Arriola, Larraitz, Balkau, Beverley, Boeing, Heiner, Deloukas, Panos, Forouhi, Nita G., Franks, Paul W., Grioni, Sara, Kaaks, Rudolf, Key, Timothy J., Navarro, Carmen, Nilsson, Peter M., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, Jose Ramón, Riboli, Elio, Rolandsson, Olov, Sacerdote, Carlotta, Salamanca-Fernandez, Elena, Slimani, Nadia, Spijkerman, Annemieke M W, Tjonneland, Anne, Tumino, Rosario, Van Der A, Daphne L., Van Der Schouw, Yvonne T., McCarthy, Mark I., Barroso, Inês, O'Rahilly, Stephen, Savage, David B., Sattar, Naveed, Langenberg, Claudia, Scott, Robert A., and Wareham, Nicholas J.

Published
2016

34. Association Between Low-Density Lipoprotein Cholesterol–Lowering Genetic Variants and Risk of Type 2 Diabetes

Author

Lotta, Luca A., primary, Sharp, Stephen J., additional, Burgess, Stephen, additional, Perry, John R. B., additional, Stewart, Isobel D., additional, Willems, Sara M., additional, Luan, Jian’an, additional, Ardanaz, Eva, additional, Arriola, Larraitz, additional, Balkau, Beverley, additional, Boeing, Heiner, additional, Deloukas, Panos, additional, Forouhi, Nita G., additional, Franks, Paul W., additional, Grioni, Sara, additional, Kaaks, Rudolf, additional, Key, Timothy J., additional, Navarro, Carmen, additional, Nilsson, Peter M., additional, Overvad, Kim, additional, Palli, Domenico, additional, Panico, Salvatore, additional, Quirós, Jose-Ramón, additional, Riboli, Elio, additional, Rolandsson, Olov, additional, Sacerdote, Carlotta, additional, Salamanca-Fernandez, Elena, additional, Slimani, Nadia, additional, Spijkerman, Annemieke M. W., additional, Tjonneland, Anne, additional, Tumino, Rosario, additional, van der A, Daphne L., additional, van der Schouw, Yvonne T., additional, McCarthy, Mark I., additional, Barroso, Inês, additional, O’Rahilly, Stephen, additional, Savage, David B., additional, Sattar, Naveed, additional, Langenberg, Claudia, additional, Scott, Robert A., additional, and Wareham, Nicholas J., additional

Published
2016
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35. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author

Wood, Angela M., Kaptoge, Stephen, Butterworth, Adam S., Willeit, Peter, Warnakula, Samantha, Bolton, Thomas, Paige, Ellie, Paul, Dirk S., Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi, Verschuren, W. M. Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Salomaa, Veikko, Nordestgaard, Børge G., Yeap, Bu B., Fletcher, Astrid, Melander, Olle, Kuller, Lewis H., Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyrus, Arndt, Volker, Franco, Oscar H., Wennberg, Patrik, Gallacher, John, Gómez De La Cámara, Agustín, Völzke, Henry, Dahm, Christina C., Dale, Caroline E., Bergmann, Manuela M., Crespo, Carlos J., Van Der Schouw, Yvonne T., Kaaks, Rudolf, Simons, Leon A., Lagiou, Pagona, Schoufour, Josje D., Boer, Jolanda M. A., Key, Timothy J., Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W., Taylor, James O., Sacerdote, Carlotta, Wallace, Robert B., Quiros, J. Ramon, Tumino, Rosario, Blazer II, Dan G., Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J., Psaty, Bruce M., Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M., Grioni, Sara, Palli, Domenico, Huerta, José M., Price, Jackie F., Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C., Panagiotakos, Demosthenes B., Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E., Barrett-Connor, Elizabeth, Van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nicholas J., Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J., Sakurai, Masaru, Shaw, Jonathan E., Knuiman, Matthew W., Voortman, Trudy, Meisinger, Christa, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J., Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F., Ford, Ian, Sattar, Naveed, Lazo, Mariana, Thompson, Simon G., Ferrari, Pietro, Leon, David A., Davey-Smith, George, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, and Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group

Subjects
Cardiovascular system--Diseases, Drinking of alcoholic beverages, Mortality, Diseases--Risk factors, 3. Good health
Abstract

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.

36. Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes: a meta-analysis

Author

Kim Overvad, Mark I. McCarthy, Larraitz Arriola, Olov Rolandsson, Heiner Boeing, Rudolf Kaaks, John R. B. Perry, Carmen Navarro, Peter M. Nilsson, Elena Salamanca-Fernández, Inês Barroso, Sara Grioni, Elio Riboli, Sara M. Willems, Claudia Langenberg, Timothy J. Key, David B. Savage, Beverley Balkau, Luca A. Lotta, Domenico Palli, Nadia Slimani, Isobel D. Stewart, Paul W. Franks, Anne Tjønneland, Stephen Burgess, Jian'an Luan, Annemieke M.W. Spijkerman, Robert A. Scott, Stephen J. Sharp, Salvatore Panico, Rosario Tumino, Yvonne T. van der Schouw, Eva Ardanaz, Nicholas J. Wareham, Panos Deloukas, Daphne L. van der A, Naveed Sattar, Carlotta Sacerdote, José Ramón Quirós, Stephen O'Rahilly, Nita G. Forouhi, Sharp, Stephen [0000-0003-2375-1440], Burgess, Stephen [0000-0001-5365-8760], Perry, John [0000-0001-6483-3771], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Barroso, Ines [0000-0001-5800-4520], O'Rahilly, Stephen [0000-0003-2199-4449], Savage, David [0000-0002-7857-7032], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Lotta, Luca A, Sharp, Stephen J, Burgess, Stephen, Perry, John R. B, Stewart, Isobel D, Willems, Sara M, Luan, Jian'An, Ardanaz, Eva, Arriola, Larraitz, Balkau, Beverley, Boeing, Heiner, Deloukas, Pano, Forouhi, Nita G, Franks, Paul W, Grioni, Sara, Kaaks, Rudolf, Key, Timothy J, Navarro, Carmen, Nilsson, Peter M, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, Jose Ramón, Riboli, Elio, Rolandsson, Olov, Sacerdote, Carlotta, Salamanca Fernandez, Elena, Slimani, Nadia, Spijkerman, Annemieke M. W, Tjonneland, Anne, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Mccarthy, Mark I, Barroso, Inê, O'Rahilly, Stephen, Savage, David B, Sattar, Naveed, Langenberg, Claudia, Scott, Robert A, and Wareham, Nicholas J.

Subjects
0301 basic medicine, Oncology, Simvastatin, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, Cohort Studies, 0302 clinical medicine, Odds Ratio, ATP Binding Cassette Transporter, Subfamily G, Member 5, Non-U.S. Gov't, Medicine(all), Research Support, Non-U.S. Gov't, 11 Medical And Health Sciences, General Medicine, Middle Aged, 3. Good health, Drug Therapy, Combination, lipids (amino acids, peptides, and proteins), Proprotein Convertase 9, Adult, Risk, medicine.medical_specialty, Lipoproteins, Research Support, 03 medical and health sciences, General & Internal Medicine, Internal medicine, Diabetes mellitus, Genetic variation, medicine, Journal Article, Humans, Allele, Genetic Association Studies, Genetic association, Aged, Polymorphism, Genetic, business.industry, PCSK9, Genetic Variation, Membrane Proteins, Membrane Transport Proteins, Odds ratio, Cholesterol, LDL, medicine.disease, Ezetimibe, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Receptors, LDL, Hydroxymethylglutaryl CoA Reductases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Meta-Analysis
Abstract

IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near $\textit{NPC1L1}$ or $\textit{HMGCR}$, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near $\textit{HMGCR}$ are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near $\textit{NPC1L1}$ are associated with the risk of type 2 diabetes. OBJECTIVE: To investigate whether LDL-C-lowering alleles in or near $\textit{NPC1L1}$ and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, $\textit{HMGCR}$, $\textit{PCSK9}$, $\textit{ABCG5/G8}$, $\textit{LDLR}$) are associated with the risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016. EXPOSURES: Low-density lipoprotein cholesterol-lowering alleles in or near $\textit{NPC1L1}$, $\textit{HMGCR}$, $\textit{PCSK9}$, $\textit{ABCG5/G8}$, and $\textit{LDLR}$. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) for type 2 diabetes and coronary artery disease. RESULTS: Low-density lipoprotein cholesterol-lowering genetic variants at $\textit{NPC1L1}$ were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95% CI, 0.42-0.88]; $P$ = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95% CI, 1.70-3.43]; $P$ < .001). For $\textit{PCSK9}$ genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95% CI, 1.02-1.38; $P$ = .03). For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk ($I^2$ = 0% for heterogeneity in genetic associations; $P$ = .93). However, associations with type 2 diabetes were heterogeneous ($I^2$ = 77.2%; $P$ = .002), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles. CONCLUSIONS AND RELEVANCE: In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near $\textit{NPC1L1}$ and other genes was associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.

Published
2016
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