01.01. Investigación y comunicación científica

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Sat, 01 Oct 2016 00:00:00 GMT

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort Molina-Montes, Esther; Sánchez, María-José; Zamora-Ros, Raul; Romieu, Isabelle; Scalbert, Augustin; Cross, Amanda-J; Lu, Yunxia; Riboli, Elio; Bueno-de-Mesquita, H-B(as); Wark, Petra-A; Obon-Santacana, Mireia; Duell, Eric-J; Kuehn, Tilman; Katzke, Verena; Travis, Ruth-C; Ye, Weimin; Sund, Malin; Naccarati, Alessio; Mattiello, Amalia; Krogh, Vittorio; Martorana, Caterina; Masala, Giovanna; Amiano, Pilar; Huerta-Castaño, José-María; Barricarte, Aurelio; Quiros, José-Ramon; Asli, Lene-Angell; Skeie, Guri; Weiderpass, Elisabete; Ericson, Ulrika; Sonestedt, Emily; Peeters, Petra-H; Overvad, Kim; Clemens, Matthias; Boeing, Heiner; Peppa, Eleni; Vidalis, Pavlos; Trichopoulou, Antonia; Khaw, Kay-Tee; Wareham, Nick; Olsen, Anja; Tjonneland, Anne; Boutroun-Rualt, Marie-Christine; Clavel-Chapelon, Francoise Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Thu, 07 Apr 2016 00:00:00 GMT

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation Hunter, David-J; Gusev, Alexander; Shi, Huwenbo; Kichaev, Gleb; Pomerantz, Mark; Long, Henry-W; Freedman, Matthew-L; Li, Fugen; Ingles, Sue-A; Casey, Graham; Stram, Daniel-O; Kittles, Rick-A; Strom, Sara-S; Nemesure, Barbara; Leske, M-Cristina; Wu, Suh-Yuh; Isaacs, William-B; Price, Alkes-L; Pettaway, Curtis-A; Yeboah, Edward-D; Tettey, Yao; Biritwum, Richard-B; Adjei, Andrew-A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand-P; John, Esther-M; Hsing, Ann-W; Chu, Lisa; Murphy, Adam-B; Carpten, John; Hennis, Anslem-J-M; Goodman, Phyllis-J; Klein, Eric-A; Witte, John-S; Kaggwa, Sam; Cook, Michael-B; Berndt, Sonja-I; Hoover, Robert; Yeager, Meredith; Kote-Jarai, ZSofia; Guy, Michelle; Govindasami, Koveela; Leongamornlert, Daniel; Sawyer, Emma-J; Wilkinson, Rosemary; Saunders, Edward-J; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Morgan, Angela; Fisher, Cyril; Hazel, Steve; Livni, Naomi; Eeles, Rosalind-A; Easton, Douglas; Al-Olama, Ali-Amin; Benlloch, Sara; Cook, Margaret; Muir, Kenneth; Lophatananon, Artitaya; Fitzgerald, Liesel-M; Giles, Graham-G; Hopper, John-L; Southey, Melissa-C; Gronberg, Henrik; Wiklund, Fredrik; Adolfson, Jan; Stattin, Paer; Johansson, Jan-Erik; Cavalli-Bjoerkman, Carin; Karlsson, Ami; Broms, Michael; Aly, Markus; Henderson, Brian-E; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo-L-J; Weischer, Maren; Nordestgaard, Borge-G; Nielsen, Sune-F; Key, Tim-J; Travis, Ruth-C; Neal, David-E; Donovan, Jenny-L; Brown, Paul; George, Anne; Marsden, Gemma; Lane, Athene; Davis, Michael; Hamdy, Freddie-C; Pharoah, Paul; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet-L; Thibodeau, Stephen-N; McDonnell, Shannon-K; Schaid, Daniel-J; Tillmans, Lori; Riska, Shaun; Wang, Liang; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Rinckleb, Antje; Herkommer, Kathleen; Kibel, Adam-S; Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Lubiski, Jan; Cannon-Albright, Lisa; Teerlink, Craig; Arndt, Volker; Brenner, Hermann; Dieffenbach, Aida-K; Park, Jong-Y; Sellers, Thomas-A; Pow-Sang, Julio; Park, Hyun; Radlein, Selina; Rincon, María; Haley, James; Zachariah, Babu; Lin, Hui-Yi; Slavov, Chavdar; Popov, Elenko; Kaneva, Radka; Mitev, Vanio; Kachakova, Darina; Mitkova, Atanaska; Batra, Jyotsna; Clements, Judith-A; Heathcote, Peter; Wood, Glenn; Malone, Greg; Saunders, Pamela; Eckert, Allison; Yeadon, Trina; Kerr, Kris; Collins, Angus; Turner, Megan; Srinivasan, Srilakshmi; Kedda, Mary-Anne; Alexander, Kimberly; Omara, Tracy; Spurdle, Amanda; Paulo, Paula; Maia, Sofia; Henrique, Rui; Pinto, Pedro; Santos, Joana; Barros-Silva, Joao; Teixeira, Manuel-R; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Vlahova, Aleksandrina; Dikov, Tihomir; Christova, Svetlana; Conti, David-V; Schumacher, Frederick-R; Haiman, Christopher-A; Albanes, Demetrius; Berg, Christine; Overvad, Kim; Campa, Daniele; Crawford, E-David; Diver, W-Ryan; Gapstur, Susan-M; Stevens, Victoria-L; Gaziano, J-Michael; Giovannucci, Edward; Johansson, Mattias; Kraft, Peter; Lindstrom, Sara; Le-Marchand, Loic; Riboli, Elio; Siddiq, Afshan; Trichopoulos, Dimitrios; Vineis, Paolo; Trynka, Gosia; Raychaudhuri, Soumya; Pasaniuc, Bogdan; Pedersen, John; Auvinen, Anssi; Kujala, Paula; Maeaettaenen, Liisa; Murtola, Teemu; Taari, Kimmo; Klarskov, Peter; Roder, Andreas; Iversen, Peter; Wallinder, Hans; Gustafsson, Sven; Cox, Angela; Zheng, Wei; Signorello, Lisa-B; Blot, William-J; Stegmaier, Christa; Wu, Huihai Although genome-wide association studies have identified over 100 risk loci that explain ?33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

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)

Tue, 05 Apr 2016 00:00:00 GMT

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) Murphy, Neil; Cross, Amanda-J; Riboli, Elio; Abubakar, Mustapha; Jenab, Mazda; Freisling, Heinz; Kong, So-Yeon; Muller, David-C; Gunter, Marc-J; Aleksandrova, Krasimira; Boutron-Ruault, Marie-Christine; Dossus, Laure; Racine, Antoine; Kuehn, Tilman; Katzke, Verena-A; Tjonneland, Anne; Petersen, Kristina-E-N; Overvad, Kim; Ramon-Quiros, J; Jakszyn, Paula; Molina-Montes, Esther; Dorronsoro, Miren; Huerta-Castaño, José-María; Barricarte, Aurelio; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth-C; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Masala, Giovanna; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Siersema, Peter-D; Bueno-de-Mesquita, H-Bas; Peeters, Petra-H; Ohlsson, Bodil; Ericson, Ulrika; Palmqvist, Richard; Nystrom, Hanna; Skeie, Guri; Weiderpass, Elisabete; Tsilidis, Kostas BACKGROUND: Obesity 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 FINDINGS: The 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 <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS: These 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.

Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

Tue, 01 Mar 2016 00:00:00 GMT

Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study Wark, Petra-A; Ward, Heather-A; Middleton, Lefkos; Riboli, Elio; Vineis, Paolo; Gallo, Valentina; Vanacore, Nicola; Bueno-de-Mesquita, H-Bas; Vermeulen, Roel; Brayne, Carol; Wareham, Nicholas; Pearce, Neil; Ferrari, Pietro; Jenab, Mazda; Andersen, Peter-M; Wennberg, Patrik; Katzke, Verena; Kaaks, Rudolf; Weiderpass, Elisabete; Peeters, Petra-H; Mattiello, Amalia; Pala, Valeria; Barricante, Aurelio; Chirlaque-López, María-Dolores; Travier, Noemie; Travis, Ruth-C; Sánchez, María-José; Pessah-Rasmussen, Helene; Petersson, Jesper; Tjonneland, Anne; Tumino, Rosario; Ramon-Quiros, José; Trichopoulou, Antonia; Oikonomidou, Despoina; Kyrozis, Andreas; Masala, Giovanna; Sacerdote, Carlotta; Arriola, Larraitz; Boeing, Heiner; Vigl, Matthaeus; Claver-Chapelon, Francoise Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the European Prospective Investigation into Cancer and Nutrition. A total of 472,100 individuals were included in the analysis, yielding 219 ALS deaths. At recruitment, information on PA was collected thorough standardised questionnaires. Total PA was expressed by the Cambridge Physical Activity Index (CPAI) and analysed in relation to ALS mortality, using Cox hazard models. Interactions with age, sex, and anthropometric measures were assessed. Total PA was weakly inversely associated with ALS mortality with a borderline statistically significant trend across categories (p = 0.042), with those physically active being 33% less likely to die from ALS compared to those inactive: HR = 0.67 (95% CI 0.42-1.06). Anthropometric measures, sex, and age did not modify the association with CPAI. The present study shows a slightly decreased-not increased like in case-control studies-risk of dying from ALS in those with high levels of total PA at enrolment. This association does not appear confounded by age, gender, anthropometry, smoking, and education. Ours was the first prospective cohort study on ALS and physical activity.