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1. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.

Author

Ju-Sheng Zheng, Jian'an Luan, Eleni Sofianopoulou, Stephen J Sharp, Felix R Day, Fumiaki Imamura, Thomas E Gundersen, Luca A Lotta, Ivonne Sluijs, Isobel D Stewart, Rupal L Shah, Yvonne T van der Schouw, Eleanor Wheeler, Eva Ardanaz, Heiner Boeing, Miren Dorronsoro, Christina C Dahm, Niki Dimou, Douae El-Fatouhi, Paul W Franks, Guy Fagherazzi, Sara Grioni, José María Huerta, Alicia K Heath, Louise Hansen, Mazda Jenab, Paula Jakszyn, Rudolf Kaaks, Tilman Kühn, Kay-Tee Khaw, Nasser Laouali, Giovanna Masala, Peter M Nilsson, Kim Overvad, Anja Olsen, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Miguel Rodríguez-Barranco, Carlotta Sacerdote, Annemieke M W Spijkerman, Tammy Y N Tong, Rosario Tumino, Konstantinos K Tsilidis, John Danesh, Elio Riboli, Adam S Butterworth, Claudia Langenberg, Nita G Forouhi, and Nicholas J Wareham

Subjects
Medicine
Abstract

BackgroundPrior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis.Methods and findingsWe performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.ConclusionsOur study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

Published
2020
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2. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Author

Ju-Sheng Zheng, Stephen J. Sharp, Fumiaki Imamura, Albert Koulman, Matthias B. Schulze, Zheng Ye, Jules Griffin, Marcela Guevara, José María Huerta, Janine Kröger, Ivonne Sluijs, Antonio Agudo, Aurelio Barricarte, Heiner Boeing, Sandra Colorado-Yohar, Courtney Dow, Miren Dorronsoro, Pia T. Dinesen, Guy Fagherazzi, Paul W. Franks, Edith J. M. Feskens, Tilman Kühn, Verena Andrea Katzke, Timothy J. Key, Kay-Tee Khaw, Maria Santucci de Magistris, Francesca Romana Mancini, Elena Molina-Portillo, Peter M. Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, Jose Ramón Quirós, Olov Rolandsson, Fulvio Ricceri, Annemieke M. W. Spijkerman, Nadia Slimani, Giovanna Tagliabue, Anne Tjonneland, Rosario Tumino, Yvonne T. van der Schouw, Claudia Langenberg, Elio Riboli, Nita G. Forouhi, and Nicholas J. Wareham

Subjects
Saturated fatty acids, Odd-chain, Even-chain, Very-long-chain, Metabolic markers, Lipids, Medicine
Abstract

Abstract Background Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. Methods We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Results Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Conclusions Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

Published
2017
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3. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Author

Veronika Fedirko, Hao Quang Tran, Andrew T. Gewirtz, Magdalena Stepien, Antonia Trichopoulou, Krasimira Aleksandrova, Anja Olsen, Anne Tjønneland, Kim Overvad, Franck Carbonnel, Marie-Christine Boutron-Ruault, Gianluca Severi, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Christina Bamia, Pagona Lagiou, Sara Grioni, Salvatore Panico, Domenico Palli, Rosario Tumino, Alessio Naccarati, Petra H. Peeters, H. B. Bueno-de-Mesquita, Elisabete Weiderpass, José María Huerta Castaño, Aurelio Barricarte, María-José Sánchez, Miren Dorronsoro, J. Ramón Quirós, Antonio Agudo, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Kathryn E. Bradbury, Kay-Tee Khaw, Nick Wareham, Konstantinos K. Tsilidis, Dagfinn Aune, Augustin Scalbert, Isabelle Romieu, Elio Riboli, and Mazda Jenab

Subjects
Hepatocellular carcinoma, Lipopolysaccharide, Flagellin, Endotoxins, Prospective studies, Medicine
Abstract

Abstract Background Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. Methods We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Results Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70–81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. Conclusions These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

Published
2017
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4. Prevalencia y factores asociados con la duración de la lactancia materna exclusiva durante los 6 primeros meses en la cohorte INMA de Guipúzcoa

Author

Madalen Oribe, Aitana Lertxundi, Mikel Basterrechea, Haizea Begiristain, Loreto Santa Marina, María Villar, Miren Dorronsoro, Pilar Amiano, and Jesús Ibarluzea

Subjects
Lactancia materna, Lactancia materna exclusiva, Abandono precoz de la lactancia materna, Factores de riesgo, Hipogalactia, Escasa ganancia de peso, Public aspects of medicine, RA1-1270
Abstract

Objetivos: Estimar la prevalencia de la lactancia materna exclusiva en la cohorte INMA (Infancia y Medio Ambiente) de Guipúzcoa durante los primeros 6 meses de vida del bebé. Identificar las razones de su abandono y determinar los factores asociados. Método: La población de estudio está formada por 638 mujeres embarazadas (www.proyectoinma.org) seguidas desde el primer trimestre de embarazo hasta los 14 meses de edad de sus hijos. Para determinar los factores asociados con el abandono de la lactancia materna exclusiva se utilizan modelos de regresión logística en dos etapas diferentes (4 meses/fase temprana y 6 meses/fase tardía). Resultados: La prevalencia de lactancia materna exclusiva fue del 84,8% al alta hospitalaria, el 53,7% a los 4 meses y el 15,4% a los 6 meses de vida. Las razones descritas por las madres sobre el abandono de la lactancia materna exclusiva asociadas a la fase temprana son problemas de lactancia, escasa ganancia de peso e hipogalactia. Otros factores que influyen en la etapa temprana son la intención previa durante el embarazo de dar lactancia materna exclusiva, la paridad, la comarca de residencia y la clase social. En la etapa tardía influye el tiempo de baja por maternidad. Conclusiones: Los resultados de este estudio pueden ser de utilidad para los profesionales sanitarios y desde una perspectiva de salud pública, ya que permiten diseñar estrategias para apoyar a las madres lactantes, teniendo en cuenta las razones principales de abandono temprano y tras la reincorporación a la vida laboral.

Published
2015
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5. The association between adult attained height and sitting height with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Author

Norie Sawada, Petra A Wark, Melissa A Merritt, Shoichiro Tsugane, Heather A Ward, Sabina Rinaldi, Elisabete Weiderpass, Laureen Dartois, Mathilde His, Marie-Christine Boutron-Ruault, Renée Turzanski-Fortner, Rudolf Kaaks, Kim Overvad, María-Luisa Redondo, Noemie Travier, Elena Molina-Portillo, Miren Dorronsoro, Lluis Cirera, Eva Ardanaz, Aurora Perez-Cornago, Antonia Trichopoulou, Pagona Lagiou, Elissavet Valanou, Giovanna Masala, Valeria Pala, Petra Hm Peeters, Yvonne T van der Schouw, Olle Melander, Jonas Manjer, Marisa da Silva, Guri Skeie, Anne Tjønneland, Anja Olsen, Marc J Gunter, Elio Riboli, and Amanda J Cross

Subjects
Medicine, Science
Abstract

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.

Published
2017
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6. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Author

Neil Murphy, Amanda J Cross, Mustapha Abubakar, Mazda Jenab, Krasimira Aleksandrova, Marie-Christine Boutron-Ruault, Laure Dossus, Antoine Racine, Tilman Kühn, Verena A Katzke, Anne Tjønneland, Kristina E N Petersen, Kim Overvad, J Ramón Quirós, Paula Jakszyn, Esther Molina-Montes, Miren Dorronsoro, José-María Huerta, Aurelio Barricarte, Kay-Tee Khaw, Nick Wareham, Ruth C Travis, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Giovanna Masala, Vittorio Krogh, Rosario Tumino, Paolo Vineis, Salvatore Panico, H Bas Bueno-de-Mesquita, Peter D Siersema, Petra H Peeters, Bodil Ohlsson, Ulrika Ericson, Richard Palmqvist, Hanna Nyström, Elisabete Weiderpass, Guri Skeie, Heinz Freisling, So Yeon Kong, Kostas Tsilidis, David C Muller, Elio Riboli, and Marc J Gunter

Subjects
Medicine
Abstract

BackgroundObesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.Methods and findingsThe association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of ConclusionsThese results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Published
2016
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7. Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study.

Author

Véronique Chajès, Carine Biessy, Pietro Ferrari, Isabelle Romieu, Heinz Freisling, Inge Huybrechts, Augustin Scalbert, Bas Bueno de Mesquita, Dora Romaguera, Marc J Gunter, Paolo Vineis, Camilla Plambeck Hansen, Marianne Uhre Jakobsen, Françoise Clavel-Chapelon, Guy Fagherazzi, Marie-Christine Boutron-Ruault, Verana Katzke, Jasmine Neamat-Allah, Heiner Boeing, Ursula Bachlechner, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Valeria Pala, Giovanna Masala, Amalia Mattiello, Guri Skeie, Elisabete Weiderpass, Antonio Agudo, Jose Maria Huerta, Eva Ardanaz, Maria Jose Sánchez, Miren Dorronsoro, Jose Ramon Quirós, Ingegerd Johansson, Anna Winkvist, Emily Sonested, Tim Key, Kay-Tee Khaw, Nicolas J Wareham, Petra H M Peeters, and Nadia Slimani

Subjects
Medicine, Science
Abstract

BACKGROUND:Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS:Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS:In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend

Published
2015
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8. El estudio prospectivo europeo sobre cáncer y nutrición (EPIC)

Author

Carlos A. González, Carmen Navarro, Carmen Martínez, José R. Quirós, Miren Dorronsoro, Aurelio Barricarte, María José Tormo, Antonio Agudo, María Dolores Chirlaque, Pilar Amiano, Eva Ardanaz, Guillem Pera, María José Sánchez, and Antonio Berenguer

Subjects
Medicine, Public aspects of medicine, RA1-1270
Abstract

EPIC es un estudio prospectivo multicéntrico coordinado por la Agencia Internacional de Investigación del Cancer (IARC) de la OMS, que se inició en 1993 con la recogida de datos y muestras de sangre en 23 centros de 10 países europeos: Alemania, Dinamarca, España, Francia, Grecia, Holanda, Italia, Noruega, Reino Unido y Suecia, En España se realiza en 5 áreas geográficas: Asturias, Granada, Guipúzcoa, Murcia y Navarra. Se incluyeron en la cohorte 519.978 individuos (de los cuales 366.521 son mujeres) y en 385.719 de ellos se dispone de muestras de sangre por análisis de laboratorio. Hasta la fecha se han identificado 24.195 casos incidentes de cáncer. Los resultados de la comparación del consumo alimentario entre los 23 centros europeos se han publicado en el 2002, en un suplemento de una revista europea de Nutrición. Los primeros resultados obtenidos en EPIC sobre la relación de la dieta y el cáncer muestran un efecto protector del consumo de fibras, frutas y verduras sobre el cáncer colo-rectal, un efecto protector del consumo de frutas sobre el cáncer de pulmón, y de las frutas y verduras sobre el tracto digestivo superior, mientras que se ha confirmado que el alto consumo de frutas y verduras no tiene efecto sobre el cáncer de próstata. Usando un diario de 7 días para evaluar el consumo de grasas saturadas, se ha confirmado que un alto consumo de estas aumenta el riesgo de cáncer de mama.

Published
2004

9. Consumption of dairy products and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Author

Neil Murphy, Teresa Norat, Pietro Ferrari, Mazda Jenab, Bas Bueno-de-Mesquita, Guri Skeie, Anja Olsen, Anne Tjønneland, Christina C Dahm, Kim Overvad, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Laura Nailler, Rudolf Kaaks, Birgit Teucher, Heiner Boeing, Manuela M Bergmann, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Valeria Pala, Rosario Tumino, Paolo Vineis, Salvatore Panico, Petra H M Peeters, Vincent K Dik, Elisabete Weiderpass, Eiliv Lund, Jose Ramon Quiros Garcia, Raul Zamora-Ros, Maria José Sánchez Pérez, Miren Dorronsoro, Carmen Navarro, Eva Ardanaz, Jonas Manjer, Martin Almquist, Ingegerd Johansson, Richard Palmqvist, Kay-Tee Khaw, Nick Wareham, Timothy J Key, Francesca L Crowe, Veronika Fedirko, Marc J Gunter, and Elio Riboli

Subjects
Medicine, Science
Abstract

Prospective studies have consistently reported lower colorectal cancer risks associated with higher intakes of total dairy products, total milk and dietary calcium. However, less is known about whether the inverse associations vary for individual dairy products with differing fat contents.In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between intakes of total milk and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and dietary calcium with colorectal cancer risk amongst 477,122 men and women. Dietary questionnaires were administered at baseline. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for relevant confounding variables.During the mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred. After multivariable adjustments, total milk consumption was inversely associated with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98). Similar inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI: 0.82-0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02) in the multivariable models. Inverse associations were observed for cheese and yoghurt in the categorical models; although in the linear models, these associations were non-significant. Dietary calcium was inversely associated with colorectal cancer risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99); this association was limited to dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99), with no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00, 95% CI: 0.81-1.24).Our results strengthen the evidence for a possible protective role of dairy products on colorectal cancer risk. The inverse associations we observed did not differ by the fat content of the dairy products considered.

Published
2013
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10. Development and validation of a risk score predicting substantial weight gain over 5 years in middle-aged European men and women.

Author

Annika Steffen, Thorkild I A Sørensen, Sven Knüppel, Noemie Travier, María-José Sánchez, José María Huerta, J Ramón Quirós, Eva Ardanaz, Miren Dorronsoro, Birgit Teucher, Kuanrong Li, H Bas Bueno-de-Mesquita, Daphne van der A, Amalia Mattiello, Domenico Palli, Rosario Tumino, Vittorio Krogh, Paolo Vineis, Antonia Trichopoulou, Philippos Orfanos, Dimitrios Trichopoulos, Bo Hedblad, Peter Wallström, Kim Overvad, Jytte Halkjær, Anne Tjønneland, Guy Fagherazzi, Laureen Dartois, Francesca Crowe, Kay-Tee Khaw, Nick Wareham, Lefkos Middleton, Anne M May, Petra H M Peeters, and Heiner Boeing

Subjects
Medicine, Science
Abstract

BACKGROUND:Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population. METHODS:We used lifestyle and nutritional data from 53°758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining ≥ 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample). RESULTS:Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of ≥ 200 points were 9% and 96%, respectively. CONCLUSION:The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score.

Published
2013
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11. Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC).

Author

Neil Murphy, Teresa Norat, Pietro Ferrari, Mazda Jenab, Bas Bueno-de-Mesquita, Guri Skeie, Christina C Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Antoine Racine, Rudolf Kaaks, Birgit Teucher, Heiner Boeing, Manuela M Bergmann, Antonia Trichopoulou, Dimitrios Trichopoulos, Pagona Lagiou, Domenico Palli, Valeria Pala, Salvatore Panico, Rosario Tumino, Paolo Vineis, Peter Siersema, Franzel van Duijnhoven, Petra H M Peeters, Anette Hjartaker, Dagrun Engeset, Carlos A González, Maria-José Sánchez, Miren Dorronsoro, Carmen Navarro, Eva Ardanaz, José R Quirós, Emily Sonestedt, Ulrika Ericson, Lena Nilsson, Richard Palmqvist, Kay-Tee Khaw, Nick Wareham, Timothy J Key, Francesca L Crowe, Veronika Fedirko, Petra A Wark, Shu-Chun Chuang, and Elio Riboli

Subjects
Medicine, Science
Abstract

BACKGROUND:Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. METHODOLOGY/PRINCIPAL FINDINGS:After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. CONCLUSIONS/SIGNIFICANCE:Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.

Published
2012
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12. IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3).

Author

Alpa V Patel, Iona Cheng, Federico Canzian, Loïc Le Marchand, Michael J Thun, Christine D Berg, Julie Buring, Eugenia E Calle, Stephen Chanock, Francoise Clavel-Chapelon, David G Cox, Miren Dorronsoro, Laure Dossus, Christopher A Haiman, Susan E Hankinson, Brian E Henderson, Robert Hoover, David J Hunter, Rudolf Kaaks, Laurence N Kolonel, Peter Kraft, Jakob Linseisen, Eiliv Lund, Jonas Manjer, Catherine McCarty, Petra H M Peeters, Malcolm C Pike, Michael Pollak, Elio Riboli, Daniel O Stram, Anne Tjonneland, Ruth C Travis, Dimitrios Trichopoulos, Rosario Tumino, Meredith Yeager, Regina G Ziegler, Heather Spencer Feigelson, and Breast and Prostate Cancer Cohort Consortium

Subjects
Medicine, Science
Abstract

IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-I and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-I and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-I levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women.

Published
2008
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13. Supplementary Table 1 from Metabolic Syndrome and Risks of Colon and Rectal Cancer: The European Prospective Investigation into Cancer and Nutrition Study

Author

Tobias Pischon, Konstantinos K Tsilidis, Naomi E. Allen, Nicholas Wareham, Kay-Tee Khaw, Richard Palmqvist, Göran Hallmans, Aurelio Barricarte, Jose-María Huerta, Miren Dorronsoro, María-José Sánchez, Genevieve Buckland, Laudina Rodríguez, Petra H. Peeters, Christina Bamia, Androniki Naska, Antonia Trichopoulou, Annekatrin Lukanova, Rudolf Kaaks, Paolo Vineis, Rosario Tumino, Salvatore Panico, Claudia Agnoli, Giovanna Masala, Sophie Morois, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Anne Tjønneland, Anja Olsen, Jane Nautrup Østergaard, Kim Overvad, Dora Romaguera, Elio Riboli, Isabelle Romieu, Sabina Rinaldi, Veronika Fedirko, Fränzel J.B. van Duijnhoven, Eugene Jansen, H. Bas Bueno-de-Mesquita, Mazda Jenab, Heiner Boeing, and Krasimira Aleksandrova

Abstract

PDF file - 96K

Published
2023

14. Supplementary Figures Legends from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author

Laura Beretta, Pierre Hainaut, Mazda Jenab, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Miren Dorronsoro, Diana Gavrila, Eva Ardanaz, Emilio Sánchez-Cantalejo, Antonio Agudo, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B(as). Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Domenico Palli, Valeria Pala, Christina Bamia, Pagona Lagiou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Renee Turzanski-Fortner, Marie-Christine Boutron-Ruault, Gianluca Severi, Laura Baglietto, Anne Tjønneland, Anja Olsen, Kim Overvad, David Muller, Amelie Plymoth, Magdalena Stepien, Sandeep Misra, and Talita Duarte-Salles

Abstract

Supplementary Figures Legends

Published
2023

15. Supplementary Tables from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author

Laura Beretta, Pierre Hainaut, Mazda Jenab, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Miren Dorronsoro, Diana Gavrila, Eva Ardanaz, Emilio Sánchez-Cantalejo, Antonio Agudo, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B(as). Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Domenico Palli, Valeria Pala, Christina Bamia, Pagona Lagiou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Renee Turzanski-Fortner, Marie-Christine Boutron-Ruault, Gianluca Severi, Laura Baglietto, Anne Tjønneland, Anja Olsen, Kim Overvad, David Muller, Amelie Plymoth, Magdalena Stepien, Sandeep Misra, and Talita Duarte-Salles

Abstract

Supplementary Tables

Published
2023

16. Perspective on This Article from Anthropometric Measures, Physical Activity, and Risk of Glioma and Meningioma in a Large Prospective Cohort Study

Author

Elio Riboli, Paolo Vineis, Isabelle Romieu, Ruth C. Travis, Naomi E. Allen, Nick Wareham, Kay-Tee Khaw, Signe Borgquist, Jonas Manjer, Beatrice S. Melin, Göran Hallmans, Eric J. Duell, Laudina Rodríguez, Maria José Sánchez, Miren Dorronsoro, Maria-Dolores Chirlaque, Aurelio Barricarte, Anne M. May, Petra H. M. Peeters, H. Bas Bueno-de-Mesquita, Amalia Mattiello, Rosario Tumino, Domenico Palli, Claudia Agnoli, Carlotta Sacerdote, Andreas Kyrozis, Christina Bamia, Antonia Trichopoulou, Annika Steffen, Heiner Boeing, Brigit Teucher, Christina C. Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Brigitte Schlehofer, Valentina Gallo, Gerald Bové, and Dominique S. Michaud

Abstract

Perspective on This Article from Anthropometric Measures, Physical Activity, and Risk of Glioma and Meningioma in a Large Prospective Cohort Study

Published
2023

17. Data from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author

Laura Beretta, Pierre Hainaut, Mazda Jenab, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Miren Dorronsoro, Diana Gavrila, Eva Ardanaz, Emilio Sánchez-Cantalejo, Antonio Agudo, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B(as). Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Domenico Palli, Valeria Pala, Christina Bamia, Pagona Lagiou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Renee Turzanski-Fortner, Marie-Christine Boutron-Ruault, Gianluca Severi, Laura Baglietto, Anne Tjønneland, Anja Olsen, Kim Overvad, David Muller, Amelie Plymoth, Magdalena Stepien, Sandeep Misra, and Talita Duarte-Salles

Abstract

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case–control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and α-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14–1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. Cancer Prev Res; 9(9); 758–65. ©2016 AACR.

Published
2023

18. Plasma levels of OPN (ng/ml) in HCC Cases and matched Controls. from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author

Laura Beretta, Pierre Hainaut, Mazda Jenab, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Miren Dorronsoro, Diana Gavrila, Eva Ardanaz, Emilio Sánchez-Cantalejo, Antonio Agudo, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B(as). Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Domenico Palli, Valeria Pala, Christina Bamia, Pagona Lagiou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Renee Turzanski-Fortner, Marie-Christine Boutron-Ruault, Gianluca Severi, Laura Baglietto, Anne Tjønneland, Anja Olsen, Kim Overvad, David Muller, Amelie Plymoth, Magdalena Stepien, Sandeep Misra, and Talita Duarte-Salles

Abstract

Plasma levels of OPN (ng/ml) in HCC Cases and matched Controls.

Published
2023

19. Cubic spline for the association between OPN levels and HCC from Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author

Laura Beretta, Pierre Hainaut, Mazda Jenab, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Miren Dorronsoro, Diana Gavrila, Eva Ardanaz, Emilio Sánchez-Cantalejo, Antonio Agudo, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B(as). Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Domenico Palli, Valeria Pala, Christina Bamia, Pagona Lagiou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Renee Turzanski-Fortner, Marie-Christine Boutron-Ruault, Gianluca Severi, Laura Baglietto, Anne Tjønneland, Anja Olsen, Kim Overvad, David Muller, Amelie Plymoth, Magdalena Stepien, Sandeep Misra, and Talita Duarte-Salles

Abstract

Multivariable adjusted odds ratio (continuous line) and 95% CI (dotted line) are shown for the continuous levels of OPN values associated to HCC. Reference value was set at 47.15 ng/ml (the optimal cut-off point) for all subjects. For better visibility, the levels were truncated at 1 and 99 percentile of distribution.

Published
2023

20. Data from Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Mazda Jenab, W. Robert Bruce, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Pietro Ferrari, Faidra Stavropoulou, Heinz Freisling, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Mårten Werner, Miren Dorronsoro, Aurelio Barricarte, José María Huerta Castaño, María-José Sánchez, Núria Sala, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B. Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Vittorio Krogh, Domenico Palli, Effie Vasilopoulou, Maria Kritikou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Tilman Kühn, Aurélie Affret, Nadia Bastide, Marie-Christine Boutron-Ruault, Kim Overvad, Anja Olsen, Anne Tjønneland, Isabelle Romieu, Veronika Fedirko, Gail McKeown-Eyssen, Andrew T. Gewirtz, Hao Quang Tran, and So Yeon Kong

Abstract

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk.Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin- and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors.Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (Pinteraction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10–2.51; Ptrend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47–1.02; Ptrend, 0.18).Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist.Impact: Further studies are warranted to better clarify these preliminary observations. Cancer Epidemiol Biomarkers Prev; 25(2); 291–301. ©2016 AACR.

Published
2023

21. Data from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition.Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples.Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02–1.84, and OR = 1.50; 95% CI, 1.09–2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81–1.29).Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking.Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055–65. ©2013 AACR.

Published
2023

22. Supplementary Table 5 from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

PDF - 80KB, Association of smoking and occupational exposure with bladder cancer by NAT2 acetylation in cases and controls from EPIC.

Published
2023

23. Supplementary Figure 1 from Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

Author

Rudolf Kaaks, Federico Canzian, Magdalena Stepien, So Yeon Kong, Talita Duarte-Salles, Elisabete Weiderpass, Mie Jareid, Eiliv Lund, Weimin Ye, Malin Sund, Peter M. Nilsson, Petra H. Peeters, H.B. Bueno-de-Mesquita, Afshan Siddiq, Elio Riboli, Paolo Vineis, Salvatore Panico, Alessio Naccarati, Rosario Tumino, Valeria Pala, Domenico Palli, Ruth C. Travis, Nicholas Wareham, Kay-Tee Khaw, Miren Dorronsoro, Eva Ardanaz, José María Huerta, Esther Molina-Montes, Eric J. Duell, J. Ramón Quirós, Heiner Boeing, Dimitrios Trichopoulos, Nikos Yiannakouris, Antonia Trichopoulou, Verena A. Katzke, Alexandra Nieters, Gianluca Severi, Antoine Racine, Marie-Christine Boutron-Ruault, Immaculata De Vivo, Björn Mergarten, and Daniele Campa

Abstract

Supplementary Figure 1 - non-linear relation with 4 knots restricted cubic spline between LTL and pancreatic cancer risk.

Published
2023

24. Supplementary Table 3 from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

PDF - 63KB, NAT2 variants and bladder cancer risk for 607 cases and 695 controls nested in EPIC.

Published
2023

25. Supplemental Tables S1-S3 from Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Mazda Jenab, W. Robert Bruce, Elio Riboli, Amanda J. Cross, Marc J. Gunter, Pietro Ferrari, Faidra Stavropoulou, Heinz Freisling, Kathryn E. Bradbury, Kay-Tee Khaw, Nicholas J. Wareham, Mårten Werner, Miren Dorronsoro, Aurelio Barricarte, José María Huerta Castaño, María-José Sánchez, Núria Sala, J. Ramón Quirós, Elisabete Weiderpass, Petra H. Peeters, H.B. Bueno-de-Mesquita, Alessio Naccarati, Rosario Tumino, Amalia Mattiello, Vittorio Krogh, Domenico Palli, Effie Vasilopoulou, Maria Kritikou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Rudolf Kaaks, Tilman Kühn, Aurélie Affret, Nadia Bastide, Marie-Christine Boutron-Ruault, Kim Overvad, Anja Olsen, Anne Tjønneland, Isabelle Romieu, Veronika Fedirko, Gail McKeown-Eyssen, Andrew T. Gewirtz, Hao Quang Tran, and So Yeon Kong

Abstract

Supplemental Table S1: ORs (95% CI) for risk of CRC by quartiles of baseline biomarkers of anti-LPS- and antiflagellin- IgA and IgG. Supplemental Table S2: ORs (95% CI) for risk of CRC by increasing levels of total bacterial exposure and high sensitivity C-reactive protein, waist circumference, BMI, total dietary fat, and alcohol intake; stratified by sex. Supplemenetal Table S3: ORs (95% CI) for risk of CRC by quartile of baseline biomarkers of anti-LPS- and antiflagellin- IgA and IgG after excluding cases and controls that occurred in the first 2 years of follow-up, stratified by sex

Published
2023

26. Data from Prediagnostic 25-Hydroxyvitamin D, VDR and CASR Polymorphisms, and Survival in Patients with Colorectal Cancer in Western European Populations

Author

Mazda Jenab, Dora Romaguera, Petra A. Wark, James McKay, Isabelle Romieu, Nick Wareham, Kay-Tee Khaw, Francesca Crowe, Timothy J. Key, Göran Hallmans, Richard Palmqvist, Catalina Bonet, Miren Dorronsoro, Maria José Sánchez, Jose Ramón Quirós, Aurelio Barricarte, Maria-Dolores Chirlaque, Magritt Brustad, Guri Skeie, Petra H. Peeters, Peter D. Siersema, Rosario Tumino, Domenico Palli, Salvatore Panico, Paolo Vineis, Sara Grioni, Dimitrios Trichopoulos, Vassiliki Benetou, Antonia Trichopoulou, Krasimira Aleksandrova, Heiner Boeing, Birgit Teucher, Annekatrin Lukanova, Antoine Racine, Françoise Clavel-Chapelon, Marie-Christine Boutron-Ruault, Kim Overvad, Christina C. Dahm, Eugène H.J.M. Jansen, Teresa Norat, Fränzel J.B. van Duijnhoven, H. Bas Bueno-de-Mesquita, Anja Olsen, Pietro Ferrari, Anne Tjønneland, Elio Riboli, and Veronika Fedirko

Abstract

Background: Individuals with higher blood 25-hydroxyvitamin D [25(OH)D] levels have a lower risk of developing colorectal cancer (CRC), but the influence of 25(OH)D on mortality after CRC diagnosis is unknown.Methods: The association between prediagnostic 25(OH)D levels and CRC-specific (N = 444) and overall mortality (N = 541) was prospectively examined among 1,202 participants diagnosed with CRC between 1992 and 2003 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate HRs and corresponding 95% CIs according to 25(OH)D quintiles and genetic variation within the VDR and CASR genes. Potential dietary, lifestyle, and metabolic effect modifiers were also investigated.Results: There were 541 deaths, 444 (82%) due to CRC. Mean follow-up was 73 months. In multivariable analysis, higher 25(OH)D levels were associated with a statistically significant reduction in CRC-specific (Ptrend = 0.04) and overall mortality (Ptrend = 0.01). Participants with 25(OH)D levels in the highest quintile had an adjusted HR of 0.69 (95% CI: 0.50–0.93) for CRC-specific mortality and 0.67 (95% CI: 0.50–0.88) for overall mortality, compared with the lowest quintile. Except for a possible interaction by prediagnostic dietary calcium intake (Pinteraction = 0.01), no other potential modifying factors related to CRC survival were noted. The VDR (FokI and BsmI) and CASR (rs1801725) genotypes were not associated with survival.Conclusions: High prediagnostic 25(OH)D levels are associated with improved survival of patients with CRC.Impact: Our findings may stimulate further research directed at investigating the effects of blood vitamin D levels before, at, and after CRC diagnosis on outcomes in CRC patients. Cancer Epidemiol Biomarkers Prev; 21(4); 582–93. ©2012 AACR.

Published
2023

27. Supplementary Table 4 from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

PDF - 73KB, Joint effects of NAT2 acetylation status and occupational exposure to aromatic amines on the risk of bladder cancer (492 cases and 569 controls).

Published
2023

28. Supplementary Table 1 from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

PDF - 84KB, Association of working in at-risk occupations with bladder cancer in men (609 cases and 665 controls) and women (145 cases and 168 controls) from EPIC.

Published
2023

29. Supplementary Table 1 from Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

Author

Rudolf Kaaks, Federico Canzian, Magdalena Stepien, So Yeon Kong, Talita Duarte-Salles, Elisabete Weiderpass, Mie Jareid, Eiliv Lund, Weimin Ye, Malin Sund, Peter M. Nilsson, Petra H. Peeters, H.B. Bueno-de-Mesquita, Afshan Siddiq, Elio Riboli, Paolo Vineis, Salvatore Panico, Alessio Naccarati, Rosario Tumino, Valeria Pala, Domenico Palli, Ruth C. Travis, Nicholas Wareham, Kay-Tee Khaw, Miren Dorronsoro, Eva Ardanaz, José María Huerta, Esther Molina-Montes, Eric J. Duell, J. Ramón Quirós, Heiner Boeing, Dimitrios Trichopoulos, Nikos Yiannakouris, Antonia Trichopoulou, Verena A. Katzke, Alexandra Nieters, Gianluca Severi, Antoine Racine, Marie-Christine Boutron-Ruault, Immaculata De Vivo, Björn Mergarten, and Daniele Campa

Abstract

Supplementary Table 1 - Associations between LTL and pancreatic cancer risk adjusted for smoking status C-peptide and HbA1c levels

Published
2023

30. Supplementary Table 2 from N-acetyltransferase 2 Phenotype, Occupation, and Bladder Cancer Risk: Results from the EPIC Cohort

Author

Paolo Vineis, Thomas Brüning, Elio Riboli, Isabelle Romieu, Pietro Ferrari, Timothy J. Key, Nick Wareham, Kay-Tee Khaw, Roy Ehrnström, David Ulmert, Mattias Johansson, Börje Ljungberg, Aurelio Barricarte, Carmen Navarro, Miren Dorronsoro, Mariá José Sánchez, Carlos González, José Ramón Quirós, Salvatore Panico, Rosario Tumino, Sabina Sieri, Domenico Palli, Dimitrios Trichopoulos, Steffen Weikert, Heiner Boeing, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Kim Overvad, Anne Tjønneland, Nina Roswall, Jenny Chang-Claude, Rudolf Kaaks, Martine M. Ros, Bas Bueno-de-Mesquita, Norman Klopp, Thomas Illig, Jürgen Angerer, Hui Ding, Hans-Peter Rihs, Swaantje Casjens, Tobias Weiss, Sylvia Rabstein, Katarzyna Gawrych, and Beate Pesch

Abstract

PDF - 84KB, Joint effects of smoking and occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons on the risk of bladder cancer (754 cases and 833 controls).

Published
2023

31. Supplementary Table 2 from Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study

Author

Rudolf Kaaks, Federico Canzian, Magdalena Stepien, So Yeon Kong, Talita Duarte-Salles, Elisabete Weiderpass, Mie Jareid, Eiliv Lund, Weimin Ye, Malin Sund, Peter M. Nilsson, Petra H. Peeters, H.B. Bueno-de-Mesquita, Afshan Siddiq, Elio Riboli, Paolo Vineis, Salvatore Panico, Alessio Naccarati, Rosario Tumino, Valeria Pala, Domenico Palli, Ruth C. Travis, Nicholas Wareham, Kay-Tee Khaw, Miren Dorronsoro, Eva Ardanaz, José María Huerta, Esther Molina-Montes, Eric J. Duell, J. Ramón Quirós, Heiner Boeing, Dimitrios Trichopoulos, Nikos Yiannakouris, Antonia Trichopoulou, Verena A. Katzke, Alexandra Nieters, Gianluca Severi, Antoine Racine, Marie-Christine Boutron-Ruault, Immaculata De Vivo, Björn Mergarten, and Daniele Campa

Abstract

Supplementary Table 2 - Associations between LTL and pancreatic cancer risk adjusted for Cpeptide and HbA1c levels considering only microscopically confirmed cases.

Published
2023

32. Supplementary Table 5 from The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease

Author

Ludmila Prokunina-Olsson, Nathaniel Rothman, Debra T. Silverman, Stephen M. Hewitt, Stephen J. Chanock, Joseph Fraumeni, William Wheeler, Laurie Burdette, Amy Hutchinson, Charles C. Chung, Xiang Deng, Zhaoming Wang, H. Barton Grossman, Giuseppe Mastrangelo, Cecilia Arici, Sofia Pavanello, Angela Carta, Stefano Porru, Eva Comperat, Morgan Roupret, Geraldine Cancel-Tassin, Olivier Cussenot, Christopher A. Haiman, Jian-Min Yuan, David Van Den Berg, Malcolm C. Pike, Mariana C. Stern, Manuela Gago-Dominguez, David V. Conti, Victoria K. Cortessis, Rebecca J. Rodabough, Chancellor Hohensee, Charles Kooperberg, Jarmo Virtamo, Stephanie J. Weinstein, Demetrius Albanes, W. Ryan Diver, Eric J. Jacobs, Susan M. Gapstur, Sara Lindstrom, Peter Kraft, David Hunter, Edward Govannucci, Immaculata De Vivo, Constance Chen, Jennifer Prescott, Elio Riboli, Jenny Chang-Claude, Paul Brennan, Anne Tjønneland, Ruth C. Travis, Miren Dorronsoro, Vittorio Krogh, Elisabete Weiderpass, Gianluca Severi, Börje Ljungberg, Dimitrios Trichopoulos, H. Bas Bueno-de-Mesquita, Afshan Siddiq, Paolo Vineis, Neil E. Caporaso, Maria T. Landi, Amanda Black, Robert L. Grubb, Gerald L. Andriole, Mark Purdue, Xifeng Wu, Josep Lloreta, Reina Garcia-Closas, Alfredo Carrato, Consol Serra, Adonina Tardon, Manolis Kogevinas, Nuria Malats, GM Monawar Hosain, Masatoshi Kida, Michael A. Jones, Liliana Guedez, Alan Schned, Adam Mumy, Alison Johnson, McAnthony Tarway, Margaret R. Karagas, Andrea B. Apolo, Molly Schwenn, Kris Ylaya, Ashley Paquin, Dalsu Baris, Brian Muchmore, Montserrat Garcia-Closas, Alexandra Scott-Johnson, Nilanjan Chatterjee, Patricia Porter-Gill, Wei Tang, Jonine D. Figueroa, Petra Lenz, Lee E. Moore, Indu Kohaar, and Yi-Ping Fu

Abstract

Association between CCNE1 variants and bladder cancer

Published
2023

33. Data from TP53 and KRAS2 Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study

Author

Pierre Hainaut, Elio Riboli, Rudolf Kaaks, Rodolfo Saracci, Timothy J. Key, Nicholas E. Day, Göran Hallmans, José Ramón Quirós, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro, Carmen Martinez, Guillem Pera, Petra H. Peeters, H. Bas Bueno-de-Mesquita, Salvatore Panico, Rosario Tumino, Vittorio Krogh, Domenico Palli, Antonia Trichopoulou, Heiner Boeing, Françoise Clavel-Chapelon, Eiliv Lund, Anne Tjønneland, Kim Overvad, Alison Dunning, Christian Malaveille, Herman Autrup, Luisa Airoldi, Armelle Munnia, Simonetta Guarrera, Seymour Garte, Marco Peluso, Emilie Le Roux, Elodie Caboux, Fabrizio Veglia, Giuseppe Matullo, Paolo Vineis, and Emmanuelle Gormally

Abstract

In cancer patients, plasma often contains mutant DNA released by cancer cells. We have assessed the significance of plasma DNA mutations for subsequent cancer development in healthy subjects in a large longitudinal prospective study. The European Prospective Investigation into Cancer and Nutrition study was analyzed with a nested case-control design. Cases were nonsmokers or ex-smokers for >10 years and newly diagnosed with lung, bladder, or upper aerodigestive tract cancers or leukemia accrued after a median follow-up of 6.3 years. Controls were matched 2:1 for follow-up, age, sex, area of recruitment, and smoking status. KRAS2 mutations were detected by mutant-enriched PCR and sequencing (n = 1,098). TP53 mutations were detected by denaturing high-performance liquid chromatography, temporal temperature gradient electrophoresis, and sequencing (n = 550). KRAS2 or TP53 mutations were detected in 13 of 1,098 (1.2%) and 20 of 550 (3.6%) subjects, respectively, 16 of whom developed cancer on average after 18.3 months of follow-up. Among 137 subjects who developed bladder cancer, 5 had KRAS2 mutations [odds ratio (OR), 4.25; 95% confidence interval (95% CI), 1.27-14.15] and 7 had TP53 mutations (OR, 1.81; 95% CI, 0.66-4.97). There was a nonsignificant trend for association between TP53 mutations and bulky adducts in lymphocyte DNA (OR, 2.78; 95% CI, 0.64-12.17). This is the first report of TP53 or KRAS2 mutations in the plasma of healthy subjects in a prospective study, suggesting that KRAS2 mutation is detectable ahead of bladder cancer diagnosis. TP53 mutation may be associated with environmental exposures. These observations have implications for monitoring early steps of carcinogenesis. (Cancer Res 2006; 66(13): 6871-6)

Published
2023

34. Supplementary Figures 1-5 from Intragenic ATM Methylation in Peripheral Blood DNA as a Biomarker of Breast Cancer Risk

Author

James M. Flanagan, Robert Brown, Kay-Tee Khaw, Rudolf Kaaks, Dimitrios Trichopoulos, N. Charlotte Onland-Moret, Salvatore Panico, Francoise Clavel-Chapelon, Miren Dorronsoro, Paolo Vineis, Elio Riboli, Heather Thorne, Anthony Swerdlow, Alan Ashworth, Michael Jones, Olivia Fletcher, Nick Orr, Montserrat Garcia-Closas, and Kevin Brennan

Abstract

PDF file - 207K

Published
2023

35. Supplementary Table 1 from TP53 and KRAS2 Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study

Author

Pierre Hainaut, Elio Riboli, Rudolf Kaaks, Rodolfo Saracci, Timothy J. Key, Nicholas E. Day, Göran Hallmans, José Ramón Quirós, Carmen Navarro, Aurelio Barricarte, Miren Dorronsoro, Carmen Martinez, Guillem Pera, Petra H. Peeters, H. Bas Bueno-de-Mesquita, Salvatore Panico, Rosario Tumino, Vittorio Krogh, Domenico Palli, Antonia Trichopoulou, Heiner Boeing, Françoise Clavel-Chapelon, Eiliv Lund, Anne Tjønneland, Kim Overvad, Alison Dunning, Christian Malaveille, Herman Autrup, Luisa Airoldi, Armelle Munnia, Simonetta Guarrera, Seymour Garte, Marco Peluso, Emilie Le Roux, Elodie Caboux, Fabrizio Veglia, Giuseppe Matullo, Paolo Vineis, and Emmanuelle Gormally

Abstract

Supplementary Table 1 from TP53 and KRAS2 Mutations in Plasma DNA of Healthy Subjects and Subsequent Cancer Occurrence: A Prospective Study

Published
2023

36. Supplementary Figure Legends 1-5, Tables 1-4 from Intragenic ATM Methylation in Peripheral Blood DNA as a Biomarker of Breast Cancer Risk

Author

James M. Flanagan, Robert Brown, Kay-Tee Khaw, Rudolf Kaaks, Dimitrios Trichopoulos, N. Charlotte Onland-Moret, Salvatore Panico, Francoise Clavel-Chapelon, Miren Dorronsoro, Paolo Vineis, Elio Riboli, Heather Thorne, Anthony Swerdlow, Alan Ashworth, Michael Jones, Olivia Fletcher, Nick Orr, Montserrat Garcia-Closas, and Kevin Brennan

Abstract

PDF file - 130K

Published
2023

37. Supplementary Materials, Figures 1 - 3, Tables 1 - 4, 6 - 8 from The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease

Author

Ludmila Prokunina-Olsson, Nathaniel Rothman, Debra T. Silverman, Stephen M. Hewitt, Stephen J. Chanock, Joseph Fraumeni, William Wheeler, Laurie Burdette, Amy Hutchinson, Charles C. Chung, Xiang Deng, Zhaoming Wang, H. Barton Grossman, Giuseppe Mastrangelo, Cecilia Arici, Sofia Pavanello, Angela Carta, Stefano Porru, Eva Comperat, Morgan Roupret, Geraldine Cancel-Tassin, Olivier Cussenot, Christopher A. Haiman, Jian-Min Yuan, David Van Den Berg, Malcolm C. Pike, Mariana C. Stern, Manuela Gago-Dominguez, David V. Conti, Victoria K. Cortessis, Rebecca J. Rodabough, Chancellor Hohensee, Charles Kooperberg, Jarmo Virtamo, Stephanie J. Weinstein, Demetrius Albanes, W. Ryan Diver, Eric J. Jacobs, Susan M. Gapstur, Sara Lindstrom, Peter Kraft, David Hunter, Edward Govannucci, Immaculata De Vivo, Constance Chen, Jennifer Prescott, Elio Riboli, Jenny Chang-Claude, Paul Brennan, Anne Tjønneland, Ruth C. Travis, Miren Dorronsoro, Vittorio Krogh, Elisabete Weiderpass, Gianluca Severi, Börje Ljungberg, Dimitrios Trichopoulos, H. Bas Bueno-de-Mesquita, Afshan Siddiq, Paolo Vineis, Neil E. Caporaso, Maria T. Landi, Amanda Black, Robert L. Grubb, Gerald L. Andriole, Mark Purdue, Xifeng Wu, Josep Lloreta, Reina Garcia-Closas, Alfredo Carrato, Consol Serra, Adonina Tardon, Manolis Kogevinas, Nuria Malats, GM Monawar Hosain, Masatoshi Kida, Michael A. Jones, Liliana Guedez, Alan Schned, Adam Mumy, Alison Johnson, McAnthony Tarway, Margaret R. Karagas, Andrea B. Apolo, Molly Schwenn, Kris Ylaya, Ashley Paquin, Dalsu Baris, Brian Muchmore, Montserrat Garcia-Closas, Alexandra Scott-Johnson, Nilanjan Chatterjee, Patricia Porter-Gill, Wei Tang, Jonine D. Figueroa, Petra Lenz, Lee E. Moore, Indu Kohaar, and Yi-Ping Fu

Abstract

Supplementary Figure 1: Electrophoretic mobility shift assays (EMSA) for CCNE1 SNPs rs8102137 and rs7257330. Supplementary Figure 2: Alignment of cyclin E protein isoforms - WT1, WT2 and ES and ET. Supplementary Figure 3: Functional analysis of cyclin E isoforms.Supplementary Table 1: Description of sub-studies included in NCI-GWAS1 and GWAS2 of bladder cancer. Supplementary Table 2: Characteristics of bladder tissue samples used for mRNA expression analysis. Supplementary Table 3: PCR primers, genotyping and gene expression assays, EMSA probes and antibodies. Supplementary Table 4: Bladder cancer stage and grade information for patients in the combined GWAS1+2 set. Supplementary Table 6: Association with bladder cancer risk with mutual adjustment for CCNE1 variants. Supplementary Table 7: Association with bladder cancer risk for CCNE1 variants previously associated with other cancers and for two non-synonymous coding variants. Supplementary Table 8: Association between cyclin E protein expression (IHC scores), bladder cancer patient characteristics and CCNE1 variants.

Published
2023

38. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author

Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium für Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository

Subjects
Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract

Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

Published
2019

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

Author

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

Subjects
Greenhouse Effect, Male, Type 2 diabetes, 010501 environmental sciences, 01 natural sciences, Chronic disease, Greenhouse Gases, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Environmental health, Vegetables, Risk of mortality, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Mortality, Prospective cohort study, Greehouse gases, 0105 earth and related environmental sciences, Red meat, business.industry, Hazard ratio, Public Health, Environmental and Occupational Health, medicine.disease, Confidence interval, Diet, Trend analysis, Diabetes Mellitus, Type 2, Food, Spain, Chronic Disease, Cohort, Female, business, Type 2
Abstract

The Author(s) 2020., [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 (

Published
2021

40. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author

Nita G. Forouhi, Kim Overvad, Ivonne Sluijs, Tammy Y.N. Tong, Christina C. Dahm, Kay-Tee Khaw, Thomas E. Gundersen, José María Huerta, Peter M. Nilsson, Miguel Rodríguez-Barranco, Nasser Laouali, Adam S. Butterworth, Giovanna Masala, Sara Grioni, Rosario Tumino, Anja Olsen, Stephen J. Sharp, Salvatore Panico, J. Ramón Quirós, Yvonne T. van der Schouw, Eleanor Wheeler, Rudolf Kaaks, Alicia K Heath, Eva Ardanaz, Felix R. Day, Eleni Sofianopoulou, Konstantinos K. Tsilidis, Luca A. Lotta, Nicholas J. Wareham, Douae El-Fatouhi, Claudia Langenberg, Heiner Boeing, Guy Fagherazzi, Paula Jakszyn, Olov Rolandsson, Rupal L. Shah, Mazda Jenab, Miren Dorronsoro, Ju-Sheng Zheng, Fumiaki Imamura, Isobel D. Stewart, Elio Riboli, Paul W. Franks, Louise Hansen, John Danesh, Carlotta Sacerdote, Jian'an Luan, Niki Dimou, Annemieke M.W. Spijkerman, Tilman Kühn, Zheng, Ju-Sheng [0000-0001-6560-4890], Sharp, Stephen J [0000-0003-2375-1440], Day, Felix R [0000-0003-3789-7651], Sluijs, Ivonne [0000-0001-7758-4911], Shah, Rupal L [0000-0001-8789-8869], van der Schouw, Yvonne T [0000-0002-4605-435X], Dahm, Christina C [0000-0003-0481-2893], Dimou, Niki [0000-0003-1678-9328], Franks, Paul W [0000-0002-0520-7604], Fagherazzi, Guy [0000-0001-5033-5966], Huerta, José María [0000-0002-9637-3869], Heath, Alicia K [0000-0001-6517-1300], Hansen, Louise [0000-0002-7109-8864], Jenab, Mazda [0000-0002-0573-1852], Kühn, Tilman [0000-0001-7702-317X], Laouali, Nasser [0000-0002-8532-456X], Masala, Giovanna [0000-0002-5758-9069], Olsen, Anja [0000-0003-4788-503X], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Sacerdote, Carlotta [0000-0002-8008-5096], Tong, Tammy YN [0000-0002-0284-8959], Tumino, Rosario [0000-0003-2666-414X], Tsilidis, Konstantinos K [0000-0002-8452-8472], Riboli, Elio [0000-0001-6795-6080], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita G [0000-0002-5041-248X], Wareham, Nicholas J [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Sharp, Stephen J. [0000-0003-2375-1440], Day, Felix R. [0000-0003-3789-7651], Shah, Rupal L. [0000-0001-8789-8869], van der Schouw, Yvonne T. [0000-0002-4605-435X], Dahm, Christina C. [0000-0003-0481-2893], Franks, Paul W. [0000-0002-0520-7604], Heath, Alicia K. [0000-0001-6517-1300], Tong, Tammy Y. N. [0000-0002-0284-8959], Tsilidis, Konstantinos K. [0000-0002-8452-8472], Forouhi, Nita G. [0000-0002-5041-248X], and Wareham, Nicholas J. [0000-0003-1422-2993]

Subjects
Male, Single Nucleotide Polymorphisms, Organic chemistry, Genome-wide association study, Type 2 diabetes, VARIANTS, 030204 cardiovascular system & hematology, Biochemistry, Endocrinology, Medical Conditions, Mathematical and Statistical Techniques, 0302 clinical medicine, DESIGN, Risk Factors, Medicine and Health Sciences, Metabolites, VITAMIN-D SUPPLEMENTATION, 030212 general & internal medicine, Prospective Studies, Vitamin D, 11 Medical and Health Sciences, RISK, Diabetis, Statistics, Diabetes, Genomics, Vitamins, General Medicine, Metaanalysis, Middle Aged, Type 2 Diabetes, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Physical sciences, Chemistry, OBESITY, Endokrinologi och diabetes, Medicine, LIFE-STYLE, Female, Life Sciences & Biomedicine, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, DATABASE, Vitamina D, European Continental Ancestry Group, Single-nucleotide polymorphism, Endocrinology and Diabetes, Research and Analysis Methods, Lower risk, White People, Chemical compounds, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Organic compounds, Diabetes Mellitus, Genome-Wide Association Studies, medicine, Vitamin D and neurology, Genetics, Humans, Statistical Methods, Science & Technology, business.industry, Biology and Life Sciences, Computational Biology, Human Genetics, Odds ratio, Mendelian Randomization Analysis, Genome Analysis, medicine.disease, Metabolism, Diabetes Mellitus, Type 2, Genetic Loci, Metabolic Disorders, Relative risk, Dietary Supplements, GENETIC-DETERMINANTS, business, Mathematics, Genètica, Genome-Wide Association Study
Abstract

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.

Published
2020

41. Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes : EPIC-InterAct case-cohort study in eight European countries

Author

Matthias B. Schulze, Peter M. Nilsson, Sara Grioni, Rosario Tumino, Stephen J. Sharp, Salvatore Panico, Ju-Sheng Zheng, Heiner Boeing, Tilman Kühn, Dagfinn Aune, Nita G. Forouhi, Kim Overvad, Olov Rolandsson, Miren Dorronsoro, Antonio Agudo, Fulvio Ricceri, Giovanna Masala, Thomas E. Gundersen, Paul W. Franks, Rajiv Chowdhury, Guy Fagherazzi, Tammy Y.N. Tong, Aurelio Barricarte, Anne Tjønneland, Nicholas J. Wareham, Ivonne Sluijs, Heinz Freisling, Kay-Tee Khaw, Annemieke M.W. Spijkerman, María Dolores Chirlaque, Adam S. Butterworth, Keren Papier, Elio Riboli, Verena Katzke, Fumiaki Imamura, John Danesh, Cecilie Kyrø, Elisabete Weiderpass, Marc J. Gunter, Nasser Laouali, J. Ramón Quirós, Yvonne T. van der Schouw, Daniel Redondo-Sanchez, Marinka Steur, Douae El-Fatouhi, Forouhi, Nita G [0000-0002-5041-248X], and Apollo - University of Cambridge Repository

Subjects
Male, Type 2 diabetes, Ascorbic Acid, MELLITUS, 0302 clinical medicine, Vegetables, 030212 general & internal medicine, Prospective Studies, LEVEL CORRELATIONS, Prospective cohort study, health care economics and organizations, RISK, Diabetis, GUT MICROBIOTA, Diabetes, Biochemical markers, Hazard ratio, Absolute risk reduction, General Medicine, CANCER, European Prospective Investigation into Cancer and Nutrition, Europe, CARDIOVASCULAR-DISEASE, Marcadors bioquímics, Endokrinologi och diabetes, Female, HEALTH, Life Sciences & Biomedicine, Type 2, Cohort study, 030209 endocrinology & metabolism, Endocrinology and Diabetes, 1117 Public Health and Health Services, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes Mellitus, medicine, Humans, METAANALYSIS, Science & Technology, VITAMIN-C, business.industry, Research, 1103 Clinical Sciences, Biomarkers, Carotenoids, Case-Control Studies, Diabetes Mellitus, Type 2, Diet, Fruit, medicine.disease, Ascorbic acid, Confidence interval, business, BETA-CAROTENE SUPPLEMENTATION, Demography
Abstract

Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. Design Prospective case-cohort study. Setting Populations from eight European countries. Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. Main outcome measure Incident type 2 diabetes. Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.

Published
2020

42. Intake of fried foods is associated with obesity in the cohort of Spanish adults from the European Prospective Investigation into Cancer and Nutrition

Author

Guallar-Castillón, Pilar, Rodríguez-Artalejo, Fernando, Fornés, Nélida Schmid, Banegas, José R, Etxezarreta, Pilar Amiano, Ardanaz, Eva, Barricarte, Aurelio, Chirlaque, María-Dolores, Iraeta, Miren Dorronsoro, Larrañaga, Nerea Larrañaga, Losada, Adamina, Mendez, Michelle, Martínez, Carmen, Quirós, José R, Navarro, Carmen, Jakszyn, Paula, Sánchez, María J, Tormo, María J, and González, Carlos A

Published
2007
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43. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

Author

Androniki Naska, Kim Overvad, Kuanrong Li, Eric J. Duell, Domenico Palli, Giovanna Tagliabue, Christina Bamia, Ingegerd Johansson, Petra H.M. Peeters, Nicholas J. Wareham, Anne Tjønneland, Paul Brennan, Bas Bueno-de-Mesquita, Kathryn E. Bradbury, Antonia Trichopoulou, Miguel Rodríguez-Barranco, Guri Skeie, Marie-Christine Boutron-Ruault, Salvatore Panico, Franco Berrino, Rosario Tumino, Verena Katzke, Marc J. Gunter, Sabine Naudin, Elisabete Weiderpass Vainio, Pietro Ferrari, Inger T. Gram, Anne Laure Védié, Elio Riboli, Aurelio Barricarte, Miren Dorronsoro, Nada Assi, Tristan Jaouen, José Ramón Quirós, Rudolf Kaaks, Heiner Boeing, Maria Dolores Chirlaque, Malin Sund, Hanna Sternby, Carlotta Sacerdote, Vinciane Rebours, and Cecilie Kyrø

Subjects
0301 basic medicine, Cancer Research, business.industry, Hazard ratio, Alcohol, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Pancreatic cancer, Medicine, Smoking status, business, Prospective cohort study, Wine intake, Demography
Abstract

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

Published
2018

44. Adipokines and inflammation markers and risk of differentiated thyroid carcinoma: The EPIC study

Author

Kim Overvad, Paolo Vineis, Ruth C. Travis, Renée T. Fortner, Raul Zamora-Ros, Miren Dorronsoro, Petra H.M. Peeters, Eva Ardanaz, Marie-Christine Boutron-Ruault, Julie A. Schmidt, María José Sánchez, Rosario Tumino, Anja Olsen, Isabelle Romieu, Silvia Franceschi, Carine Biessy, Fabrice Bonnet, Krasimira Aleksandrova, Konstantinos K. Tsilidis, Anne Tjønneland, Laure Dossus, Claudia Agnoli, Sabina Rinaldi, Antonia Trichopoulou, Carlo La Vecchia, Salvatore Panico, Maria Sandström, Agnès Fournier, Guri Skeie, Domenico Palli, Kay-Tee Khaw, Elisabete Weiderpass, Elio Riboli, Rudolf Kaaks, Lena Maria Nilsson, Anne-Sophie Navionis, H B As Bueno-de-Mesquita, Augustin Scalbert, Dagfinn Aune, Eleni Peppa, Maria-Dolores Chirlaque, and José Ramón Quirós

Subjects
0301 basic medicine, Oncology, endocrine system, Cancer Research, medicine.medical_specialty, endocrine system diseases, business.industry, Thyroid disease, Case-control study, Cancer, Adipokine, medicine.disease, Thyroid carcinoma, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, medicine, Prospective cohort study, business, Thyroid cancer
Abstract

Other than the influence of ionizing radiation and benign thyroid disease, little is known about the risk factors for differentiated thyroid cancer (TC) which is an increasing common cancer worldwi ...

Published
2017

45. Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations

Author

Rosario Tumino, Jody van den Ouweland, Kathryn E. Bradbury, Petra H.M. Peeters, Martin Almquist, Fränzel J.B. Van Duijnhoven, Anja Olsen, Giuseppe Matullo, Miren Dorronsoro, Heinz Freisling, Mazda Jenab, Weimin Ye, Eivind Ness-Jensen, Elio Riboli, Maria Dolores Chirlaque, Jonas Manjer, Marina Kvaskoff, Veronika Fedirko, Verena Katzke, H. Bas Bueno-de-Mesquita, Dagfinn Aune, Marie-Christine Boutron-Ruault, Claudia Agnoli, Mireia Obón-Santacana, Frida Renström, Elisabete Weiderpass, Claire Cadeau, Teresa Norat, Cristina Lasheras, Kay-Tee Khaw, Maria Kritikou, Salvatore Panico, Henk J. van Kranen, Karina Standahl Olsen, Nicholas J. Wareham, Anouk Halfweeg, Arnulf Langhammer, María José Sánchez, Heiner Boeing, Kim Overvad, Anne Tjønneland, Domenico Palli, Antonia Trichopoulou, Ellen Kampman, Neil Murphy, Magritt Brustad, Aurelio Barricarte, Kristian Hveem, Eric J. Duell, Peter D. Siersema, Anastasia Kotanidou, and Tilman Kühn

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, 25-Hydroxyvitamin D 2, Vitamin D and neurology, Prospective cohort study, 2. Zero hunger, business.industry, Case-control study, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Endocrinology, Oncology, chemistry, 030220 oncology & carcinogenesis, Nested case-control study, Calcifediol, business, Body mass index
Abstract

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trondelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.

Published
2017

46. Hepcidin levels and gastric cancer risk in the EPIC-EurGast study

Author

Núria Aranda, Bodil Ohlsson, Francesca Fasanelli, Heiner Boeing, Antonio Agudo, Ana Fonseca-Nunes, Fulvio Ricceri, Rosario Tumino, Domenico Palli, Aurora Perez-Cornago, Mazda Jenab, Petra H.M. Peeters, Elisabete Weiderpass, Emilio Sánchez-Cantalejo, José María Huerta, Leila Lujan-Barroso, Rudolf Kaaks, Miren Dorronsoro, H. Bas Bueno-de-Mesquita, Monica Tous, Tilman Kühn, Anja Olsen, Kim Overvad, Kay-Tee Khaw, José Maria Quirós, Klas Sjöberg, Amanda J. Cross, Marc J. Gunter, Antonia Trichopoulou, Vittorio Krogh, Anne Tjønneland, Aurelio Barricarte, Effie Vasilopoulou, Eleni Peppa, Amalia Mattiello, Victoria Arija, and Paula Jakszyn

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Hepcidin, hemic and lymphatic diseases, Internal medicine, medicine, Stomach cancer, biology, business.industry, Stomach, Confounding, nutritional and metabolic diseases, Cancer, Odds ratio, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Ferritin, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, biology.protein, business
Abstract

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

Published
2017

47. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Author

Nicholas J. Wareham, Giovanna Tagliabue, Paul Brennan, Salvatore Panico, Miguel Rodríguez-Barranco, Giuseppe Matullo, Alessio Naccarati, Stuart Sherman, Line Moi, Paolo Vineis, María Dolores Chirlaque, Marc J. Gunter, Pagona Lagiou, Rudolf Kaaks, Antonia Trichopoulou, David C. Muller, Verena Katzke, Gianluca Severi, Eva Ardanaz, Ghislaine Scelo, Vinciane Rebours, Murray Korc, H. Bas Bueno-de-Mesquita, Lill-Tove Busund, Elisabete Weiderpass, Samantha Deitz McElyea, Eric J. Duell, Rosario Tumino, Petra H.M. Peeters, Greg Cote, Marie-Christine Boutron-Ruault, Anne Tjønneland, José Ramón Quirós, Anastasia Kotanidou, Núria Sala, Dagfinn Aune, Anja Olsen, Ruth C. Travis, Kim Overvad, Domenico Palli, Leila Lujan-Barroso, Kay-Tee Khaw, Miren Dorronsoro, and Heiner Boeing

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Receiver operating characteristic, business.industry, Case-control study, Cancer, medicine.disease, Logistic regression, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pancreatic cancer, Internal medicine, Cohort, medicine, business, Prospective cohort study, Cohort study
Abstract

Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values

Published
2017

48. Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

Author

Johan Nilsson Sommar, Anne Tjønneland, Petra H.M. Peeters, Paolo Vineis, Nancy L. Pedersen, Ingeborg M. Kooter, Marloes Eeftens, Carlotta Sacerdote, Alessandro Marcon, Marie Pedersen, Claudia Galassi, Massimo Stafoggia, Andrea Jaensch, Enrica Migliore, Kirsten Thorup Eriksen, Andrei Pyko, Rob Beelen, Laura Fratiglioni, Ranjeet S. Sokhi, Bertil Forsberg, Gerard Hoek, Ming-Yi Tsai, Fulvio Ricceri, Miren Dorronsoro, Gunn Marit Aasvang, H. Bas Bueno-de-Mesquita, Meng Wang, Bernhard Föger, Zorana Jovanovic Andersen, Ulf de Faire, Kees de Hoogh, Gudrun Weinmayr, Sara Grioni, Mette Sørensen, Claes-Göran Östenson, Roel Vermeulen, Pilar Amiano, Ibon Tamayo, Michelle Plusquin, Norun Hjertager Krog, Göran Pershagen, Timothy J. Key, David Olsson, Gabriele Nagel, Bert Brunekreef, Ole Raaschou-Nielsen, Michal Korek, Vittorio Krogh, and Bente Oftedal

Subjects
Pollutant, Cancer Research, business.industry, Air pollution, Cancer, Environmental exposure, 010501 environmental sciences, Particulates, medicine.disease, medicine.disease_cause, complex mixtures, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Environmental health, Parenchyma, medicine, business, Risk assessment, Kidney cancer, 0105 earth and related environmental sciences
Abstract

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutant ...

Published
2017

49. Gallstones and incident colorectal cancer in a large pan-European cohort study

Author

Anne Tjønneland, Kim Overvad, Giovanna Masala, Marc J. Gunter, Antonia Trichopoulou, Raul Zamora-Ros, Heather Ward, Pagona Lagiou, Susana Merino, Elisabete Weiderpass, Marie-Christine Boutron-Ruault, Heinz Freisling, Rosario Tumino, Aurelio Barricarte, Dagfinn Aune, Carla H. van Gils, Gianluca Severi, Elom K. Aglago, Roel Vermeulen, Heiner Boeing, Hanna Nyström, Bas Bueno-de-Mesquita, Franck Carbonnel, Rudolf Kaaks, Amanda J. Cross, María Dolores Chirlaque, Neil Murphy, Mazda Jenab, Elio Riboli, Tilman Kühn, Martin Rutegård, Aurora Perez-Cornago, Christina Bamia, Michael F. Leitzmann, Miguel Rodríguez-Barranco, Sara Grioni, Miren Dorronsoro, Amalia Mattiello, Anja Olsen, Carlotta Sacerdote, Imperial College Trust, One Health Chemisch, and dIRAS RA-2

Subjects
Adult, Male, medicine.medical_specialty, Cancer Research, CHOLECYSTECTOMY, Population, colorectal cancer, Gallstones, DISEASE, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Journal Article, Medicine, Humans, 1112 Oncology and Carcinogenesis, Registries, Oncology & Carcinogenesis, Risk factor, education, Prospective cohort study, POPULATION, Proportional Hazards Models, RISK, education.field_of_study, Science & Technology, business.industry, Incidence, Hazard ratio, ASSOCIATION, cohort, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Oncology, 030220 oncology & carcinogenesis, Cohort, SERUM BILIRUBIN, Female, business, Colorectal Neoplasms, EPIC, Life Sciences & Biomedicine, Cohort study
Abstract

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre, and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake, and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR=1.14, 95%CI 0.99-1.31, p=0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR=0.81, 95%CI 0.63-1.04, p=0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex. This article is protected by copyright. All rights reserved.

Published
2019

50. Predicting circulating CA125 levels among healthy premenopausal women

Author

Marc J. Gunter, Agnès Fournier, Kim Overvad, David C. Muller, Eva Lundin, Hanna Sartor, Marina Kvaskoff, Louise Hansen, Domenico Palli, Renée T. Fortner, Rudolf Kaaks, J. Ramón Quirós, Miren Dorronsoro, Antonia Trichopoulou, Miguel Rodríguez-Barranco, Shelley S. Tworoger, N. Charlotte Onland-Moret, Chiara Grasso, Kathryn L. Terry, Naoko Sasamoto, Anna Karakatsani, Raina N. Fichorova, Ana Babic, Hidemi S. Yamamoto, Valeria Pala, Annika Idahl, Elisabete Weiderpass, Elio Riboli, Heiner Boeing, Daniel W. Cramer, Amalia Mattiello, Rosario Tumino, Aurelio Barricarte, Allison F. Vitonis, Eleni Peppa, Sandra Colorado-Yohar, Kay-Tee Khaw, Anne Tjønneland, Laure Dossus, Francesca Mancini, Bernard Rosner, Leila Lujan-Barroso, Timothy J. Key, and Imperial College Trust

Subjects
0301 basic medicine, Oncology, endocrine system diseases, Epidemiology, Càncer d'ovari, Ovarian cancer screening, CA-125 LEVELS, 0302 clinical medicine, Prostate, REPRODUCIBILITY, PROSTATE, Medicine, Prospective Studies, 11 Medical and Health Sciences, Early Detection of Cancer, Public, Environmental & Occupational Health, Ovarian Neoplasms, Middle Aged, Prognosis, female genital diseases and pregnancy complications, Cancer antigen, prediction model, medicine.anatomical_structure, ovarian cancer, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, Menopause, Life Sciences & Biomedicine, Menopausa, Adult, medicine.medical_specialty, MODELS, Article, 03 medical and health sciences, CA125, OVARIAN-CANCER RISK, Internal medicine, Humans, VALIDITY, Nutrició, Nutrition, Science & Technology, premenopausal, business.industry, MORTALITY, screening, Membrane Proteins, 030104 developmental biology, Premenopause, CA-125 Antigen, Case-Control Studies, Women's Health, business, LUNG, Follow-Up Studies
Abstract

Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

Published
2019

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