2,704 results on '"Severi, Gianluca"'
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452. Heterogeneous SARS-CoV-2 humoral response after COVID-19 vaccination and/or infection in the general population.
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Carrat, Fabrice, Villarroel, Paola Mariela Saba, Lapidus, Nathanael, Fourié, Toscane, Blanché, Hélène, Dorival, Céline, Nicol, Jérôme, Deleuze, Jean-François, Robineau, Olivier, SAPRIS-SERO Study Group, Zins, Marie, Severi, Gianluca, Touvier, Mathilde, de Lamballerie, Xavier, Lusivika-Nzinga, Clovis, Pannetier, Gregory, Goderel, Isabelle, Kab, Sofiane, Renuy, Adeline, and Le-Got, Stéphane
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Assessment of the intensity, dynamics and determinants of the antibody response after SARS-CoV-2 infection or vaccination in the general population is critical to guide vaccination policies. This study characterized the anti-spike IgG titers in 13,971 participants included in a French multicohort population-based serological survey on COVID-19 between April and October 2020 and followed-up with serological testing between May and October 2021. Eight follow-up profiles were defined depending on SARS-CoV-2 infection (0, 1 or 2) and COVID-19 vaccination (0, 1, 2 or 3). The anti-spike titer was lower in adults with no vaccination even in case of infection or reinfection, while it was higher in adults with infection followed by vaccination. The anti-spike titer was negatively correlated with age in vaccinated but uninfected adults, whereas it was positively correlated with age in unvaccinated but infected adults. In adults with 2 vaccine injections and no infection, the vaccine protocol, age, gender, and time since the last vaccine injection were independently associated with the anti-spike titer. The decrease in anti-spike titer was much more rapid in vaccinated than in infected subjects. These results highlight the strong heterogeneity of the antibody response against SARS-CoV-2 in the general population depending on previous infection and vaccination. [ABSTRACT FROM AUTHOR]
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- 2022
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453. Metabolic Syndrome and Risk of Gastrointestinal Cancers: An Investigation Using Large-scale Molecular Data.
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Rothwell, Joseph A., Jenab, Mazda, Karimi, Mojgan, Truong, Thérèse, Mahamat-Saleh, Yahya, Ferrari, Pietro, Dashti, S. Ghazaleh, Kühn, Tilman, Cross, Amanda J., Severi, Gianluca, Gunter, Marc J., and Murphy, Neil
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Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown. We investigated the associations between MetS and gastrointestinal cancer risk (overall, colorectal, pancreatic, esophageal adenocarcinoma, esophageal squamous cell carcinoma, stomach cardia, stomach non-cardia, hepatocellular carcinoma, and intrahepatic bile duct cancer) in 366,016 United Kingdom Biobank participants with comprehensive serum biomarker and genotype data. MetS status was determined by 3 different definitions at baseline, and, in 15,152 participants, at a repeat assessment after a median of 4.3 years of follow-up. Multivariable hazard ratios and 95% confidence intervals for cancer outcomes were estimated using Cox proportional hazards models. Analyses stratified by polygenic risk score were conducted for colorectal and pancreatic cancers. During a median follow-up of 7.1 years, 4238 incident cases of a gastrointestinal cancer occurred. MetS at baseline was associated with higher risk of overall gastrointestinal cancer by any definition (hazard ratio, 1.21; 95% confidence interval, 1.13–1.29, harmonized definition). MetS was associated with increased risks of colorectal cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer in women, and esophageal adenocarcinoma in men. Associations for colorectal cancer and pancreatic cancer did not differ by polygenic risk score strata (P -heterogeneity 0.70 and 0.69, respectively), and 80% of participants with MetS at baseline retained this status at the repeat assessment. These findings underscore the importance of maintaining good metabolic health in reducing the burden of gastrointestinal cancers, irrespective of genetic predisposition. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2022
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454. Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking.
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Petrovic, Dusan, Bodinier, Barbara, Dagnino, Sonia, Whitaker, Matthew, Karimi, Maryam, Campanella, Gianluca, Haugdahl Nøst, Therese, Polidoro, Silvia, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Lund, Eiliv, Dugué, Pierre-Antoine, Giles, Graham G., Severi, Gianluca, Southey, Melissa, Vineis, Paolo, and Stringhini, Silvia
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LUNGS ,SMOKING ,LUNG cancer ,EPIGENETICS ,CARCINOGENESIS ,DISEASE risk factors - Abstract
Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case–control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients. [ABSTRACT FROM AUTHOR]
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- 2022
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455. The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort
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Shah, Sanam, primary, MacDonald, Conor-James, additional, El Fatouhi, Douae, additional, Mahamat-Saleh, Yahya, additional, Mancini, Francesca Romana, additional, Fagherazzi, Guy, additional, Severi, Gianluca, additional, Boutron-Ruault, Marie-Christine, additional, and Laouali, Nasser, additional
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- 2021
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456. Association of Migraine With Incident Hypertension After Menopause
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MacDonald, Conor James, primary, El Fatouhi, Douae, additional, Madika, Anne-Laure, additional, Fagherazzi, Guy, additional, Kurth, Tobias, additional, Severi, Gianluca, additional, and Boutron-Ruault, Marie-Christine, additional
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- 2021
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457. Epigenetic Drift Association with Cancer Risk and Survival, and Modification by Sex
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Yu, Chenglong, primary, Wong, Ee Ming, additional, Joo, Jihoon Eric, additional, Hodge, Allison M., additional, Makalic, Enes, additional, Schmidt, Daniel, additional, Buchanan, Daniel D., additional, Severi, Gianluca, additional, Hopper, John L., additional, English, Dallas R., additional, Giles, Graham G., additional, Southey, Melissa C., additional, and Dugué, Pierre-Antoine, additional
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- 2021
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458. Long-term atmospheric exposure to PCB153 and breast cancer risk in a case-control study nested in the French E3N cohort from 1990 to 2011
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Deygas, Floriane, primary, Amadou, Amina, additional, Coudon, Thomas, additional, Grassot, Lény, additional, Couvidat, Florian, additional, Bessagnet, Bertrand, additional, Faure, Elodie, additional, Salizzoni, Pietro, additional, Gulliver, John, additional, Caudeville, Julien, additional, Severi, Gianluca, additional, Mancini, Francesca Romana, additional, Leffondré, Karen, additional, Fervers, Béatrice, additional, and Praud, Delphine, additional
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- 2021
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459. Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer
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Nguyen-Dumont, Tú, primary, Dowty, James G., additional, MacInnis, Robert J., additional, Steen, Jason A., additional, Riaz, Moeen, additional, Dugué, Pierre-Antoine, additional, Renault, Anne-Laure, additional, Hammet, Fleur, additional, Mahmoodi, Maryam, additional, Theys, Derrick, additional, Tsimiklis, Helen, additional, Severi, Gianluca, additional, Bolton, Damien, additional, Lacaze, Paul, additional, Sebra, Robert, additional, Schadt, Eric, additional, McNeil, John, additional, Giles, Graham G., additional, Milne, Roger L., additional, and Southey, Melissa C., additional
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- 2021
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460. Investigation of circulating metabolites associated with breast cancer risk by untargeted metabolomics: a case–control study nested within the French E3N cohort
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Jobard, Elodie, primary, Dossus, Laure, additional, Baglietto, Laura, additional, Fornili, Marco, additional, Lécuyer, Lucie, additional, Mancini, Francesca Romana, additional, Gunter, Marc J., additional, Trédan, Olivier, additional, Boutron-Ruault, Marie-Christine, additional, Elena-Herrmann, Bénédicte, additional, Severi, Gianluca, additional, and Rothwell, Joseph A., additional
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- 2021
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461. Psychological distress in the academic population and its association with socio-demographic and lifestyle characteristics during COVID-19 pandemic lockdown: Results from a large multicenter Italian study
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Fornili, Marco, primary, Petri, Davide, additional, Berrocal, Carmen, additional, Fiorentino, Giuseppe, additional, Ricceri, Fulvio, additional, Macciotta, Alessandra, additional, Bruno, Andreina, additional, Farinella, Domenica, additional, Baccini, Michela, additional, Severi, Gianluca, additional, and Baglietto, Laura, additional
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- 2021
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462. Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study
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Dimou, Niki, primary, Yarmolinsky, James, additional, Bouras, Emmanouil, additional, Tsilidis, Konstantinos K., additional, Martin, Richard M., additional, Lewis, Sarah J., additional, Gram, Inger T., additional, Bakker, Marije F., additional, Brenner, Hermann, additional, Figueiredo, Jane C., additional, Fortner, Renée T., additional, Gruber, Stephen B., additional, van Guelpen, Bethany, additional, Hsu, Li, additional, Kaaks, Rudolf, additional, Kweon, Sun-Seog, additional, Lin, Yi, additional, Lindor, Noralane M., additional, Newcomb, Polly A., additional, Sánchez, Maria-Jose, additional, Severi, Gianluca, additional, Tindle, Hilary A., additional, Tumino, Rosario, additional, Weiderpass, Elisabete, additional, Gunter, Marc J., additional, and Murphy, Neil, additional
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- 2021
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463. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
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Khoei, Nazlisadat Seyed, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno de Mesquita, H. Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet Bonet, Catalina, Rodríguez Barranco, Miguel, Gil, Leire, Chirlaque, María Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Pérez Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Marchand, Loïc Le, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín Sánchez, Vicente, Moreno Aguado, Víctor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D. P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl-Heinz, Freisling, Heinz, Apollo - University of Cambridge Repository, and Pharoah, Paul [0000-0001-8494-732X]
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Adult ,Male ,Nutrition and Disease ,Mendelian randomization analysis ,lcsh:Medicine ,Polymorphism, Single Nucleotide ,Antioxidants ,Càncer colorectal ,Risk Factors ,Voeding en Ziekte ,Humans ,Prospective Studies ,VLAG ,Cancer ,Aged ,lcsh:R ,Bilirubin ,Middle Aged ,Colorectal cancer ,Europe ,Case-Control Studies ,Anti-oxidants ,Female ,Colorectal Neoplasms ,Research Article - Abstract
Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10−8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. Results: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04–1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76–0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02–1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96–1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2). Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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- 2020
464. Additional file 7 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 7 Association between life course SEP on the risk of BC using complete cases in E3N [N = 39,122].
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- 2020
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465. Additional file 3 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 3. Description of all covariates selected according to the literature and tested in bivariate analyses.
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- 2020
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466. Additional file 5 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 5. Characteristics of women with available data from E3N according to SEP.
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- 2020
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467. Additional file 10 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 10 Cox proportional hazard regression of BC risk using data from multiple imputation in EPIC-Italy (N = 20,530).
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- 2020
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468. Additional file 9 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 9. Characteristics of women with available data from EPIC-Italy according to BC status and by SEP.
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- 2020
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469. Plasma concentration of brominated flame retardants and postmenopausal breast cancer risk: A nested case-control study in the French E3N cohort
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Mancini, Francesca Romana, Cano-Sancho, German, Mohamed, Oceane, Cervenka, Iris, Omichessan, Hanane, Marchand, Philippe, Boutron-Ruault, Marie-Christine, Arveux, Patrick, Severi, Gianluca, Antignac, Jean-Philippe, Kvaskoff, Marina, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Florence, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut National Du Cancer, INCa Mutuelle Générale de l'Education Nationale, MGEN Institut National de la Santé et de la Recherche Médicale, Inserm Institut National Du Cancer, INCa, and This work was realized with the data of the E3N cohort of the Inserm and supported by the Mutuelle G?n?rale de l'Education Nationale (MGEN), the Gustave Roussy Institute, and the French League against Cancer for the constitution and maintenance of the cohort. The work was also supported by the grant EQ. 9-C17014LS from the Cancer ITMO of the French National Alliance for Life and Health Sciences (AVIESAN), in collaboration with the Institut National du Cancer (French National Cancer Institute) and Inserm.
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lcsh:Public aspects of medicine ,Research ,Polybrominated Biphenyls ,lcsh:RA1-1270 ,Breast Neoplasms ,Pentabromodiphenyl ethers (PBDEs) ,Endocrine Disruptors ,Middle Aged ,Brominated flame retardants (BFRs) ,Polybrominated biphenyls (PBBs) ,Postmenopause ,lcsh:RC963-969 ,Breast cancer ,Risk Factors ,Case-Control Studies ,Biomonitoring ,lcsh:Industrial medicine. Industrial hygiene ,Halogenated Diphenyl Ethers ,E3N cohort ,Humans ,Environmental Pollutants ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,Flame Retardants - Abstract
International audience; Background: Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study. Methods: A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index. Conclusions: Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.
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- 2020
470. Chronic Low-Dose Exposure to Xenoestrogen Ambient Air Pollutants and Breast Cancer Risk: XENAIR Protocol for a Case-Control Study Nested Within the French E3N Cohort
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Amadou, Amina, Coudon, Thomas, Praud, Delphine, Salizzoni, Pietro, Leffondre, Karen, Lévêque, Emilie, Boutron-Ruault, Marie-Christine, Danjou, Aurélie M N, Morelli, Xavier, Le Cornet, Charlotte, Perrier, Lionel, Couvidat, Florian, Bessagnet, Bertrand, Caudeville, Julien, Faure, Elodie, Mancini, Francesca Romana, Gulliver, John, Severi, Gianluca, Fervers, Béatrice, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Centre Léon Bérard [Lyon], Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Institut National de l'Environnement Industriel et des Risques (INERIS), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
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hormone receptor status ,multipollutant ,air pollution ,Computer applications to medicine. Medical informatics ,R858-859.7 ,land use regression ,[SHS.ECO]Humanities and Social Sciences/Economics and Finance ,gene-environment interaction ,breast cancer ,endocrine disruptors ,Protocol ,Medicine ,geographic information system ,chemistry-transport model ,epigenetic ,ComputingMilieux_MISCELLANEOUS ,prospective study - Abstract
BackgroundBreast cancer is the most frequent cancer in women in industrialized countries. Lifestyle and environmental factors, particularly endocrine-disrupting pollutants, have been suggested to play a role in breast cancer risk. Current epidemiological studies, although not fully consistent, suggest a positive association of breast cancer risk with exposure to several International Agency for Research on Cancer Group 1 air-pollutant carcinogens, such as particulate matter, polychlorinated biphenyls (PCB), dioxins, Benzo[a]pyrene (BaP), and cadmium. However, epidemiological studies remain scarce and inconsistent. It has been proposed that the menopausal status could modify the relationship between pollutants and breast cancer and that the association varies with hormone receptor status. ObjectiveThe XENAIR project will investigate the association of breast cancer risk (overall and by hormone receptor status) with chronic exposure to selected air pollutants, including particulate matter, nitrogen dioxide (NO2), ozone (O3), BaP, dioxins, PCB-153, and cadmium. MethodsOur research is based on a case-control study nested within the French national E3N cohort of 5222 invasive breast cancer cases identified during follow-up from 1990 to 2011, and 5222 matched controls. A questionnaire was sent to all participants to collect their lifetime residential addresses and information on indoor pollution. We will assess these exposures using complementary models of land-use regression, atmospheric dispersion, and regional chemistry-transport (CHIMERE) models, via a Geographic Information System. Associations with breast cancer risk will be modeled using conditional logistic regression models. We will also study the impact of exposure on DNA methylation and interactions with genetic polymorphisms. Appropriate statistical methods, including Bayesian modeling, principal component analysis, and cluster analysis, will be used to assess the impact of multipollutant exposure. The fraction of breast cancer cases attributable to air pollution will be estimated. ResultsThe XENAIR project will contribute to current knowledge on the health effects of air pollution and identify and understand environmental modifiable risk factors related to breast cancer risk. ConclusionsThe results will provide relevant evidence to governments and policy-makers to improve effective public health prevention strategies on air pollution. The XENAIR dataset can be used in future efforts to study the effects of exposure to air pollution associated with other chronic conditions. International Registered Report Identifier (IRRID)DERR1-10.2196/15167
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471. Additional file 8 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 8 Association between life course SEP on the risk of invasive BC only using imputed data in E3N (N = 82,458).
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472. Additional file 6 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 6 Forestplot of the association of the three time point SEP and each covariate used in the fully adjusted model in E3N (N = 83,436).
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473. Additional file 1 of Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
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Nazlisadat Seyed Khoei, Mazda Jenab, Murphy, Neil, Banbury, Barbara L., Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-De-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Marie-Christine Boutron-Ruault, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Maria-Dolores Chirlaque, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Loic Le Marchand, Li, Christopher I., Li, Li, Lindblom, Annika, Noralane M. Lindor, Martín, Vicente, Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D. P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., Franzel J. B. Van Duijnhoven, Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Xuehong Zhang, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Karl-Heinz Wagner, and Freisling, Heinz
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Additional file 1 Supplementary tables 1–6, supplementary figures 1–3, supplementary text 1. Suppl. table 1 - Summary statistics for the genetic association with bilirubin levels, and sex-stratified colorectal cancer risk. Suppl. table 2 - Participating studies in the genetic consortia (GECCO/ CCFR/ and CORECT). Suppl. table 3 - Associations between unconjugated bilirubin (UCB) levels and colorectal cancer risk after different sensitivity analyses in the EPIC study. Suppl. table 4 - Results for the Mendelian randomization sensitivity analyses. Suppl. table 5 - Results for the Mendelian randomization sensitivity analyses: positive control outcomes for pancreatic cancer. Suppl. table 6 - Results for genome-wide associations of instruments with other phenotypes. Suppl. figure 1 - Cubic spline modeling of unconjugated bilirubin (UCB) levels in relation to colorectal cancer risk in the EPIC study. Suppl. figure 2 - Association between UGT1A1 polymorphism (rs6431625) and unconjugated bilirubin (UCB) levels in the EPIC study (with available GWAS data). Suppl. figure 3 - Directed acyclic graph (DAG) of the causal structure of associations between unconjugated bilirubin (UCB) levels in relation to colorectal cancer risk in the EPIC study. Suppl. text 1 - Specific funding sources and acknowledgements of participating studies.
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474. Additional file 4 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Additional file 4. Scatterplots of Schoenfeld residues for variables that do not respect the proportional risk assumption.
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475. The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Romana Mancini, Francesca, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, S., Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Boutron-Ruault, Marie Christine, Severi, Gianluca, Castagné, Raphaële, Delpierre, Cyrille, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II, Città della Salute e della Scienza University-Hospital, Ragusa Cancer Registry, Imperial College London, Italian Institute for Genomic Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer SHSESP 2017–130, This work was supported by La Ligue nationale contre le cancer [Equipe Labellisée LIGUE 2017/CD]). This study has been conducted by using data from the E3N cohort that is managed by Inserm and that has been created and is maintained thanks to the support of the MGEN, the Institute Gustave Roussy and « La Ligue contre le Cancer »., This work was supported by the French National Institute of Cancer [SHSESP 2017–130 to CD]. The funder had no role in the study design, analysis and interpretation of data and in writing the manuscript., 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), and Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
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Adult ,Lifecourse socio-economic position ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Middle Aged ,Breast cancer ,Socioeconomic Factors ,Risk Factors ,Social mobility ,Humans ,Prospective cohorts ,Aged ,Female ,Research Article - Abstract
Background Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. Methods We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. Results In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. Conclusions These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07648-w.
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476. Additional file 2 of The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Mancini, Francesca Romana, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, Sabina, Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Marie-Christine Boutron-Ruault, Severi, Gianluca, Castagné, Raphaële, and Delpierre, Cyrille
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Data_FILES - Abstract
Additional file 2. Coding specificities.
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477. Soluble Receptor for Advanced Glycation End-products (sRAGE) and colorectal cancer risk: a 1 case-control study nested within a European prospective cohort
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Aglago, Elom K., Rinaldi, Sabina, Freisling, Heinz, Jiao, Li, Hughes, David J., Fedirko, Veronika, Schalkwijk, Casper C, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Eriksen, Anne Kirstine, Kyrø, Cecilie, Boutron-Ruault, Marie-Christine, Rothwell, Joseph A., Severi, Gianluca, Katzke, Verena, Kuhn, Tilman, Schulze, Matthias B., Krasimira, Aleksandrova, Masala, Giovanna, Krogh, Vittorio, Panico, Salavatore, Tumino, Rosario, Naccarati, Alessio, Bueno-De-Mesquita, Bas, van Gils, Carla H., Sandanger, Torkjel M, Gram, Inger Torhild, Skeie, Guri, Quiros, J. Ramon, Jakszyn, Rachel, Sanchez, Maria-Jose, Amiano, Pilar, Huerta, Jose Maria, Ardanaz, Eva, Johansson, Ingegerd, Harlid, Sophia, Perez-Cornago, Aurora, Mayén, Ana-Lucia, Cordova, Reynalda, Gunter, Marc J., Vineis, Paolo, Cross, Amanda J., Riboli, Elio, and Jenab, Mazda
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VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 - Abstract
Background: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. Methods: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case–control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. Results: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59–1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42–0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68–1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82–0.99). Conclusions: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. Impact: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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478. Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
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Gentiluomo, Manuel, Katzke, Verena A, Kaaks, Rudolf, Tjonneland, Anne, Severi, Gianluca, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Ferrari, Pietro, Johnson, Theron, Schulze, Matthias B, Bergmann, Manuela, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Palli, Domenico, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Vermeulen, Roel, Sandanger, Torkjel M, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Amiano, Pilar, Colorado-Yohar, Sandra, Ardanaz, Eva, Sund, Malin, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Jakszyn, Paula, Morelli, Luca, Canzian, Federico, Campa, Daniele, Gentiluomo, Manuel, Katzke, Verena A, Kaaks, Rudolf, Tjonneland, Anne, Severi, Gianluca, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Ferrari, Pietro, Johnson, Theron, Schulze, Matthias B, Bergmann, Manuela, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Palli, Domenico, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Vermeulen, Roel, Sandanger, Torkjel M, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Amiano, Pilar, Colorado-Yohar, Sandra, Ardanaz, Eva, Sund, Malin, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Jakszyn, Paula, Morelli, Luca, Canzian, Federico, and Campa, Daniele
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BACKGROUND: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited.METHODS: To further our knowledge on this topic we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.RESULTS: We observed lower mtDNA copy number with advancing age (p=6.54×10-5) and with a high BMI level (p=0.004) and no association with sex, smoking behavior and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 0.07-0.52), p=0.001 with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses.CONCLUSIONS: Our results, suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk.IMPACT: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
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479. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis.
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Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, Murphy, Neil, Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, and Murphy, Neil
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Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
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480. Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses.
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Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L, Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J, Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria-Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K, Albanes, Demetrius, Baron, John A, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Huyghe, Jeroen R, Jenkins, Mark A, Joshi, Amit D, Kampman, Ellen, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J, Wagner, Karl-Heinz, Freisling, Heinz, Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L, Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J, Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria-Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K, Albanes, Demetrius, Baron, John A, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Huyghe, Jeroen R, Jenkins, Mark A, Joshi, Amit D, Kampman, Ellen, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J, Wagner, Karl-Heinz, and Freisling, Heinz
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BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625
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- 2020
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481. Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
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Archambault, Alexi N., Su, Yu-Ru, Jeon, Jihyoun, Thomas, Minta, Lin, Yi, Conti, David V., Win, Aung Ko, Sakoda, Lori C., Lansdorp-Vogelaar, Iris, Peterse, Elisabeth F. P., Zauber, Ann G., Duggan, David, Holowatyj, Andreana N., Huyghe, Jeroen R., Brenner, Hermann, Cotterchio, Michelle, Bezieau, Stephane, Schmit, Stephanie L., Edlund, Christopher K., Southey, Melissa C., MacInnis, Robert J., Campbell, Peter T., Chang-Claude, Jenny, Slattery, Martha L., Chan, Andrew T., Joshi, Amit D., Song, Mingyang, Cao, Yin, Woods, Michael O., White, Emily, Weinstein, Stephanie J., Ulrich, Cornelia M., Hoffmeister, Michael, Bien, Stephanie A., Harrison, Tabitha A., Hampe, Jochen, Li, Christopher I., Schafmayer, Clemens, Offit, Kenneth, Pharoah, Paul D., Moreno, Victor, Lindblom, Annika, Wolk, Alicja, Wu, Anna H., Li, Li, Gunter, Marc J., Gsur, Andrea, Keku, Temitope O., Pearlman, Rachel, Bishop, D. Timothy, Castellvi-Bel, Sergi, Moreira, Leticia, Vodicka, Pavel, Kampman, Ellen, Giles, Graham G., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D., Trichopoulou, Antonia, Severi, Gianluca, Chirlaque, Maria-Dolores, Sanchez, Maria-Jose, Palli, Domenico, Kuhn, Tilman, Murphy, Neil, Cross, Amanda J., Burnett-Hartman, Andrea N., Chanock, Stephen J., de la Chapelle, Albert, Easton, Douglas F., Elliott, Faye, English, Dallas R., Feskens, Edith J. M., FitzGerald, Liesel M., Goodman, Phyllis J., Hopper, John L., Hudson, Thomas J., Hunter, David J., Jacobs, Eric J., Joshu, Corinne E., Kury, Sebastien, Markowitz, Sanford D., Milne, Roger L., Platz, Elizabeth A., Rennert, Gad, Rennert, Hedy S., Schumacher, Fredrick R., Sandler, Robert S., Seminara, Daniela, Tangen, Catherine M., Thibodeau, Stephen N., Toland, Amanda E., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodickova, Ludmila, Potter, John D., Mannisto, Satu, Weigl, Korbinian, Figueiredo, Jane, Martin, Vicente, Larsson, Susanna C, Parfrey, Patrick S., Huang, Wen-Yi, Lenz, Heinz-Josef, Castelao, Jose E., Gago-Dominguez, Manuela, Munoz-Garzon, Victor, Mancao, Christoph, Haiman, Christopher A., Wilkens, Lynne R., Siegel, Erin, Barry, Elizabeth, Younghusband, Ban, Van Guelpen, Bethany, Harlid, Sophia, Zeleniuch-Jacquotte, Anne, Liang, Peter S., Du, Mengmeng, Casey, Graham, Lindor, Noralane M., Le Marchand, Loic, Gallinger, Steven J., Jenkins, Mark A., Newcomb, Polly A., Gruber, Stephen B., Schoen, Robert E., Hampel, Heather, Corley, Douglas A., Hsu, Li, Peters, Ulrike, Hayes, Richard B., Archambault, Alexi N., Su, Yu-Ru, Jeon, Jihyoun, Thomas, Minta, Lin, Yi, Conti, David V., Win, Aung Ko, Sakoda, Lori C., Lansdorp-Vogelaar, Iris, Peterse, Elisabeth F. P., Zauber, Ann G., Duggan, David, Holowatyj, Andreana N., Huyghe, Jeroen R., Brenner, Hermann, Cotterchio, Michelle, Bezieau, Stephane, Schmit, Stephanie L., Edlund, Christopher K., Southey, Melissa C., MacInnis, Robert J., Campbell, Peter T., Chang-Claude, Jenny, Slattery, Martha L., Chan, Andrew T., Joshi, Amit D., Song, Mingyang, Cao, Yin, Woods, Michael O., White, Emily, Weinstein, Stephanie J., Ulrich, Cornelia M., Hoffmeister, Michael, Bien, Stephanie A., Harrison, Tabitha A., Hampe, Jochen, Li, Christopher I., Schafmayer, Clemens, Offit, Kenneth, Pharoah, Paul D., Moreno, Victor, Lindblom, Annika, Wolk, Alicja, Wu, Anna H., Li, Li, Gunter, Marc J., Gsur, Andrea, Keku, Temitope O., Pearlman, Rachel, Bishop, D. Timothy, Castellvi-Bel, Sergi, Moreira, Leticia, Vodicka, Pavel, Kampman, Ellen, Giles, Graham G., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D., Trichopoulou, Antonia, Severi, Gianluca, Chirlaque, Maria-Dolores, Sanchez, Maria-Jose, Palli, Domenico, Kuhn, Tilman, Murphy, Neil, Cross, Amanda J., Burnett-Hartman, Andrea N., Chanock, Stephen J., de la Chapelle, Albert, Easton, Douglas F., Elliott, Faye, English, Dallas R., Feskens, Edith J. M., FitzGerald, Liesel M., Goodman, Phyllis J., Hopper, John L., Hudson, Thomas J., Hunter, David J., Jacobs, Eric J., Joshu, Corinne E., Kury, Sebastien, Markowitz, Sanford D., Milne, Roger L., Platz, Elizabeth A., Rennert, Gad, Rennert, Hedy S., Schumacher, Fredrick R., Sandler, Robert S., Seminara, Daniela, Tangen, Catherine M., Thibodeau, Stephen N., Toland, Amanda E., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodickova, Ludmila, Potter, John D., Mannisto, Satu, Weigl, Korbinian, Figueiredo, Jane, Martin, Vicente, Larsson, Susanna C, Parfrey, Patrick S., Huang, Wen-Yi, Lenz, Heinz-Josef, Castelao, Jose E., Gago-Dominguez, Manuela, Munoz-Garzon, Victor, Mancao, Christoph, Haiman, Christopher A., Wilkens, Lynne R., Siegel, Erin, Barry, Elizabeth, Younghusband, Ban, Van Guelpen, Bethany, Harlid, Sophia, Zeleniuch-Jacquotte, Anne, Liang, Peter S., Du, Mengmeng, Casey, Graham, Lindor, Noralane M., Le Marchand, Loic, Gallinger, Steven J., Jenkins, Mark A., Newcomb, Polly A., Gruber, Stephen B., Schoen, Robert E., Hampel, Heather, Corley, Douglas A., Hsu, Li, Peters, Ulrike, and Hayes, Richard B.
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BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to
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- 2020
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482. Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
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Christakoudi, Sofia, Kakourou, Artemisia, Markozannes, Georgios, Tzoulaki, Ioanna, Weiderpass, Elisabete, Brennan, Paul, Gunter, Marc, Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Boutron-Ruault, Marie-Christine, Madika, Anne-Laure, Severi, Gianluca, Katzke, Verena, Kuehn, Tilman, Bergmann, Manuela M., Boeing, Heiner, Karakatsani, Anna, Martimianaki, Georgia, Thriskos, Paschalis, Masala, Giovanna, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Agudo, Antonio, Redondo-Sanchez, Daniel, Colorado-Yohar, Sandra M., Mokoroa, Olatz, Melander, Ole, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Bueno-de-Mesquita, Bas, van Gils, Carla H., Vermeulen, Roel Ch, Khaw, Kay-Tee, Wareham, Nicholas J., Tong, Tammy Y. N., Freisling, Heinz, Johansson, Mattias, Lennon, Hannah, AUne, Dagfinn, Ribolil, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Tsilidis, Konstantinos K., Christakoudi, Sofia, Kakourou, Artemisia, Markozannes, Georgios, Tzoulaki, Ioanna, Weiderpass, Elisabete, Brennan, Paul, Gunter, Marc, Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Boutron-Ruault, Marie-Christine, Madika, Anne-Laure, Severi, Gianluca, Katzke, Verena, Kuehn, Tilman, Bergmann, Manuela M., Boeing, Heiner, Karakatsani, Anna, Martimianaki, Georgia, Thriskos, Paschalis, Masala, Giovanna, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Agudo, Antonio, Redondo-Sanchez, Daniel, Colorado-Yohar, Sandra M., Mokoroa, Olatz, Melander, Ole, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Bueno-de-Mesquita, Bas, van Gils, Carla H., Vermeulen, Roel Ch, Khaw, Kay-Tee, Wareham, Nicholas J., Tong, Tammy Y. N., Freisling, Heinz, Johansson, Mattias, Lennon, Hannah, AUne, Dagfinn, Ribolil, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, and Tsilidis, Konstantinos K.
- Abstract
Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
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- 2020
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483. Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer
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Yang, Tianzhong, Tang, Hongwei, Risch, Harvey A., Olson, Sarah H., Peterson, Gloria, Bracci, Paige M., Gallinger, Steven, Hung, Rayjean J., Neale, Rachel E., Scelo, Ghislaine, Duell, Eric J., Kurtz, Robert C., Khaw, Kay-Tee, Severi, Gianluca, Sund, Malin, Wareham, Nick, Amos, Christopher, I, Li, Donghui, Wei, Peng, Yang, Tianzhong, Tang, Hongwei, Risch, Harvey A., Olson, Sarah H., Peterson, Gloria, Bracci, Paige M., Gallinger, Steven, Hung, Rayjean J., Neale, Rachel E., Scelo, Ghislaine, Duell, Eric J., Kurtz, Robert C., Khaw, Kay-Tee, Severi, Gianluca, Sund, Malin, Wareham, Nick, Amos, Christopher, I, Li, Donghui, and Wei, Peng
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It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G x E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G x E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes,TRIP10andKDM3A, were identified. The aGEw test is implemented in an R package aGE.
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- 2020
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484. Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
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Huang, Joyce Y., Larose, Tricia L., Luu, Hung N., Wang, Renwei, Fanidi, Anouar, Alcala, Karine, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Caporaso, Neil E., Purdue, Mark P., Ziegler, Regina G., Freedman, Neal D., Lan, Qing, Prentice, Ross L., Pettinger, Mary, Thomson, Cynthia A., Cai, Qiuyin, Wu, Jie, Blot, William J., Shu, Xiao-Ou, Zheng, Wei, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loic, Wilkens, Lynn R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Hveem, Kristian, Xiang, Yong-Bing, Li, Hong-Lan, Gao, Yu-Tang, Visvanathan, Kala, Ueland, Per M., Midttun, Oivind, Ulvi, Arve, Buring, Julie E., Lee, I-Min, SeSS, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline, Koh, Woon-Puay, Brennan, Paul, Johansson, Mattias, Yuan, Jian-Min, Han, Jiali, Huang, Joyce Y., Larose, Tricia L., Luu, Hung N., Wang, Renwei, Fanidi, Anouar, Alcala, Karine, Stevens, Victoria L., Weinstein, Stephanie J., Albanes, Demetrius, Caporaso, Neil E., Purdue, Mark P., Ziegler, Regina G., Freedman, Neal D., Lan, Qing, Prentice, Ross L., Pettinger, Mary, Thomson, Cynthia A., Cai, Qiuyin, Wu, Jie, Blot, William J., Shu, Xiao-Ou, Zheng, Wei, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Le Marchand, Loic, Wilkens, Lynn R., Haiman, Christopher A., Zhang, Xuehong, Stampfer, Meir J., Giles, Graham G., Hodge, Allison M., Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Hveem, Kristian, Xiang, Yong-Bing, Li, Hong-Lan, Gao, Yu-Tang, Visvanathan, Kala, Ueland, Per M., Midttun, Oivind, Ulvi, Arve, Buring, Julie E., Lee, I-Min, SeSS, Howard D., Gaziano, J. Michael, Manjer, Jonas, Relton, Caroline, Koh, Woon-Puay, Brennan, Paul, Johansson, Mattias, Yuan, Jian-Min, and Han, Jiali
- Abstract
Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression., Grant numbers United States Department of Health & Human Services, National Institutes of Health (NIH) - USA, and NIH National Cancer Institute (NCI): P01CA87969, P30CA016087, R01CA092447, R01CA144034, U01CA155340, U01CA202979, UM1CA167552, UM1CA173640, UM1CA182876, UM1CA182910, UM1CA182934, UM1CA186107Grant numbers United States Department of Health & Human Services and National Institutes of Health (NIH) - USACA047988, CA097193, CA182913, CA34944, CA40360, HL043851, HL080467, HL099355, HL26490, HL34595, P30ES000260
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- 2020
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485. Autoimmunity plays a role in the onset of diabetes after 40 years of age
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Rolandsson, Olov, Hampe, Christiane S., Sharp, Stephen J., Ardanaz, Eva, Boeing, Heiner, Fagherazzi, Guy, Mancini, Francesca Romana, Nilsson, Peter M., Overvad, Kim, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Gunter, Marc J., Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Krogh, Vittorio, Kuehn, Tilman, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Sanchez, Maria-Jose, Severi, Gianluca, Spijkerman, Annemieke M. W., Tumino, Rosario, van der Schouw, Yvonne T., Riboli, Elio, Forouhi, Nita G., Langenberg, Claudia, Wareham, Nicholas J., Rolandsson, Olov, Hampe, Christiane S., Sharp, Stephen J., Ardanaz, Eva, Boeing, Heiner, Fagherazzi, Guy, Mancini, Francesca Romana, Nilsson, Peter M., Overvad, Kim, Chirlaque, Maria-Dolores, Dorronsoro, Miren, Gunter, Marc J., Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Krogh, Vittorio, Kuehn, Tilman, Palli, Domenico, Panico, Salvatore, Sacerdote, Carlotta, Sanchez, Maria-Jose, Severi, Gianluca, Spijkerman, Annemieke M. W., Tumino, Rosario, van der Schouw, Yvonne T., Riboli, Elio, Forouhi, Nita G., Langenberg, Claudia, and Wareham, Nicholas J.
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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 indica
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- 2020
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486. Exogenous hormone use and cutaneous melanoma risk in women : The European Prospective Investigation into Cancer and Nutrition
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Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnes, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjonneland, Anne, Olsen, Anja, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sanchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay-Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, Kvaskoff, Marina, Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnes, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjonneland, Anne, Olsen, Anja, Fortner, Renee T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sanchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay-Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, and Kvaskoff, Marina
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Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
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- 2020
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487. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
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Aglago, Elom K., Huybrechts, Inge, Murphy, Neil, Casagrande, Corinne, Nicolas, Genevieve, Pischon, Tobias, Fedirko, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Fournier, Agnès, Katzke, Verena, Kühn, Tilman, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Overvad, Kim, Lasheras, Cristina, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Huerta, José Maria, Ardanaz, Eva, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Bueno-de-Mesquita, Bas, May, Anne, Derksen, Jeroen W. G., Hellstrand, Sophie, Ohlsson, Bodil, Wennberg, Maria, van Guelpen, Bethany, Skeie, Guri, Brustad, Magritt, Weiderpass, Elisabete, Cross, Amanda J., Ward, Heather, Riboli, Elio, Norat, Teresa, Chajes, Veronique, Gunter, Marc J., Aglago, Elom K., Huybrechts, Inge, Murphy, Neil, Casagrande, Corinne, Nicolas, Genevieve, Pischon, Tobias, Fedirko, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Fournier, Agnès, Katzke, Verena, Kühn, Tilman, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Overvad, Kim, Lasheras, Cristina, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Huerta, José Maria, Ardanaz, Eva, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Bueno-de-Mesquita, Bas, May, Anne, Derksen, Jeroen W. G., Hellstrand, Sophie, Ohlsson, Bodil, Wennberg, Maria, van Guelpen, Bethany, Skeie, Guri, Brustad, Magritt, Weiderpass, Elisabete, Cross, Amanda J., Ward, Heather, Riboli, Elio, Norat, Teresa, Chajes, Veronique, and Gunter, Marc J.
- Abstract
BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to
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- 2020
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488. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
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Li, Chen, Stoma, Svetlana, Lotta, Luca A., Warner, Sophie, Albrecht, Eva, Allione, Alessandra, Arp, Pascal P., Broer, Linda, Buxton, Jessica L., Da Silva Couto Alves, Alexessander, Deelen, Joris, Fedko, Iryna O., Gordon, Scott D., Jiang, Tao, Karlsson, Robert, Kerrison, Nicola, Loe, Taylor K., Mangino, Massimo, Milaneschi, Yuri, Miraglio, Benjamin, Pervjakova, Natalia, Russo, Alessia, Surakka, Ida, van der Spek, Ashley, Verhoeven, Josine E., Amin, Najaf, Beekman, Marian, Blakemore, Alexandra I., Canzian, Federico, Hamby, Stephen E., Hottenga, Jouke-Jan, Jones, Peter D., Jousilahti, Pekka, Mägi, Reedik, Medland, Sarah E., Montgomery, Grant W., Nyholt, Dale R., Perola, Markus, Pietiläinen, Kirsi H., Salomaa, Veikko, Sillanpää, Elina, Suchiman, H. Eka, van Heemst, Diana, Willemsen, Gonneke, Agudo, Antonio, Boeing, Heiner, Boomsma, Dorret I., Chirlaque, Maria-Dolores, Fagherazzi, Guy, Ferrari, Pietro, Franks, Paul W., Gieger, Christian, Eriksson, Johan Gunnar, Gunter, Marc, Hagg, Sara, Hovatta, Iiris, Imaz, Liher, Kaprio, Jaakko, Kaaks, Rudolf, Key, Timothy, Krogh, Vittorio, Martin, Nicholas G., Melander, Olle, Metspalu, Andres, Moreno, Concha, Onland-Moret, N. Charlotte, Nilsson, Peter, Ong, Ken K., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Pedersen, Nancy L., Penninx, Brenda W. J. H., Quirós, J. Ramón, Riitta Jarvelin, Marjo, Rodríguez-Barranco, Miguel, Scott, Robert A., Severi, Gianluca, Slagboom, P. Eline, Spector, Tim D., Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Uitterlinden, André G., van der Schouw, Yvonne T., van Duijn, Cornelia M., Weiderpass, Elisabete, Denchi, Eros Lazzerini, Matullo, Giuseppe, Butterworth, Adam S., Danesh, John, Samani, Nilesh J., Wareham, Nicholas J., Nelson, Christopher P., Langenberg, Claudia, Codd, Veryan, Li, Chen, Stoma, Svetlana, Lotta, Luca A., Warner, Sophie, Albrecht, Eva, Allione, Alessandra, Arp, Pascal P., Broer, Linda, Buxton, Jessica L., Da Silva Couto Alves, Alexessander, Deelen, Joris, Fedko, Iryna O., Gordon, Scott D., Jiang, Tao, Karlsson, Robert, Kerrison, Nicola, Loe, Taylor K., Mangino, Massimo, Milaneschi, Yuri, Miraglio, Benjamin, Pervjakova, Natalia, Russo, Alessia, Surakka, Ida, van der Spek, Ashley, Verhoeven, Josine E., Amin, Najaf, Beekman, Marian, Blakemore, Alexandra I., Canzian, Federico, Hamby, Stephen E., Hottenga, Jouke-Jan, Jones, Peter D., Jousilahti, Pekka, Mägi, Reedik, Medland, Sarah E., Montgomery, Grant W., Nyholt, Dale R., Perola, Markus, Pietiläinen, Kirsi H., Salomaa, Veikko, Sillanpää, Elina, Suchiman, H. Eka, van Heemst, Diana, Willemsen, Gonneke, Agudo, Antonio, Boeing, Heiner, Boomsma, Dorret I., Chirlaque, Maria-Dolores, Fagherazzi, Guy, Ferrari, Pietro, Franks, Paul W., Gieger, Christian, Eriksson, Johan Gunnar, Gunter, Marc, Hagg, Sara, Hovatta, Iiris, Imaz, Liher, Kaprio, Jaakko, Kaaks, Rudolf, Key, Timothy, Krogh, Vittorio, Martin, Nicholas G., Melander, Olle, Metspalu, Andres, Moreno, Concha, Onland-Moret, N. Charlotte, Nilsson, Peter, Ong, Ken K., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Pedersen, Nancy L., Penninx, Brenda W. J. H., Quirós, J. Ramón, Riitta Jarvelin, Marjo, Rodríguez-Barranco, Miguel, Scott, Robert A., Severi, Gianluca, Slagboom, P. Eline, Spector, Tim D., Tjonneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Uitterlinden, André G., van der Schouw, Yvonne T., van Duijn, Cornelia M., Weiderpass, Elisabete, Denchi, Eros Lazzerini, Matullo, Giuseppe, Butterworth, Adam S., Danesh, John, Samani, Nilesh J., Wareham, Nicholas J., Nelson, Christopher P., Langenberg, Claudia, and Codd, Veryan
- Abstract
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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- 2020
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489. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases : a multinational cohort study
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Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., Ferrari, Pietro, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro
- Abstract
BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and
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- 2020
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490. Pre-diagnostic plasma bile acid levels and colon cancer risk : A prospective study
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Kühn, Tilman, Stepien, Magdalena, López-Nogueroles, Marina, Machado, Antje Damms, Sookthai, Disorn, Johnson, Theron, Roca, Marta, Hüsing, Anika, Maldonado, Sandra González, Cross, Amanda J, Murphy, Neil, Freisling, Heinz, Rinaldi, Sabina, Scalbert, Augustin, Fedirco, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Sowah, Solomon A, Boeing, Heiner, Jakszyn, Paula, Sánchez, Maria-Jose, Merino, Susana, Colorado-Yohar, Sandra, Barricarte, Aurelio, Khaw, Kay Tee, Schmidt, Julie A, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Thriskos, Paschalis, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Bueno-de-Mesquita, Bas, van Gils, Carla H, Heath, Alicia, Gunter, Marc J, Riboli, Elio, Lahoz, Agustín, Jenab, Mazda, Kaaks, Rudolf, Kühn, Tilman, Stepien, Magdalena, López-Nogueroles, Marina, Machado, Antje Damms, Sookthai, Disorn, Johnson, Theron, Roca, Marta, Hüsing, Anika, Maldonado, Sandra González, Cross, Amanda J, Murphy, Neil, Freisling, Heinz, Rinaldi, Sabina, Scalbert, Augustin, Fedirco, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Sowah, Solomon A, Boeing, Heiner, Jakszyn, Paula, Sánchez, Maria-Jose, Merino, Susana, Colorado-Yohar, Sandra, Barricarte, Aurelio, Khaw, Kay Tee, Schmidt, Julie A, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Thriskos, Paschalis, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Bueno-de-Mesquita, Bas, van Gils, Carla H, Heath, Alicia, Gunter, Marc J, Riboli, Elio, Lahoz, Agustín, Jenab, Mazda, and Kaaks, Rudolf
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- 2020
491. Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort
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One Health Chemisch, dIRAS RA-2, Gentiluomo, Manuel, Katzke, Verena A, Kaaks, Rudolf, Tjonneland, Anne, Severi, Gianluca, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Ferrari, Pietro, Johnson, Theron, Schulze, Matthias B, Bergmann, Manuela, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Palli, Domenico, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Vermeulen, Roel, Sandanger, Torkjel M, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Amiano, Pilar, Colorado-Yohar, Sandra, Ardanaz, Eva, Sund, Malin, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Jakszyn, Paula, Morelli, Luca, Canzian, Federico, Campa, Daniele, One Health Chemisch, dIRAS RA-2, Gentiluomo, Manuel, Katzke, Verena A, Kaaks, Rudolf, Tjonneland, Anne, Severi, Gianluca, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Weiderpass, Elisabete, Ferrari, Pietro, Johnson, Theron, Schulze, Matthias B, Bergmann, Manuela, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Palli, Domenico, Grioni, Sara, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Vermeulen, Roel, Sandanger, Torkjel M, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Amiano, Pilar, Colorado-Yohar, Sandra, Ardanaz, Eva, Sund, Malin, Khaw, Kay-Tee, Wareham, Nicholas J, Schmidt, Julie A, Jakszyn, Paula, Morelli, Luca, Canzian, Federico, and Campa, Daniele
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- 2020
492. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
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Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, Amundadottir, Laufey T., Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, and Amundadottir, Laufey T.
- Abstract
Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
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- 2020
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493. Pre-diagnostic plasma bile acid levels and colon cancer risk: A prospective study
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MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Kühn, Tilman, Stepien, Magdalena, López-Nogueroles, Marina, Machado, Antje Damms, Sookthai, Disorn, Johnson, Theron, Roca, Marta, Hüsing, Anika, Maldonado, Sandra González, Cross, Amanda J, Murphy, Neil, Freisling, Heinz, Rinaldi, Sabina, Scalbert, Augustin, Fedirco, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Sowah, Solomon A, Boeing, Heiner, Jakszyn, Paula, Sánchez, Maria-Jose, Merino, Susana, Colorado-Yohar, Sandra, Barricarte, Aurelio, Khaw, Kay Tee, Schmidt, Julie A, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Thriskos, Paschalis, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Bueno-de-Mesquita, Bas, van Gils, Carla H, Heath, Alicia, Gunter, Marc J, Riboli, Elio, Lahoz, Agustín, Jenab, Mazda, Kaaks, Rudolf, MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Kühn, Tilman, Stepien, Magdalena, López-Nogueroles, Marina, Machado, Antje Damms, Sookthai, Disorn, Johnson, Theron, Roca, Marta, Hüsing, Anika, Maldonado, Sandra González, Cross, Amanda J, Murphy, Neil, Freisling, Heinz, Rinaldi, Sabina, Scalbert, Augustin, Fedirco, Veronika, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Sowah, Solomon A, Boeing, Heiner, Jakszyn, Paula, Sánchez, Maria-Jose, Merino, Susana, Colorado-Yohar, Sandra, Barricarte, Aurelio, Khaw, Kay Tee, Schmidt, Julie A, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Thriskos, Paschalis, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Bueno-de-Mesquita, Bas, van Gils, Carla H, Heath, Alicia, Gunter, Marc J, Riboli, Elio, Lahoz, Agustín, Jenab, Mazda, and Kaaks, Rudolf
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- 2020
494. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis
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MS MDL 1, CMM Groep Burgering, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team A, Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, Murphy, Neil, MS MDL 1, CMM Groep Burgering, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Epi Kanker Team A, Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, and Murphy, Neil
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- 2020
495. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
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Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y N, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, Ferrari, Pietro, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y N, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, and Ferrari, Pietro
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- 2020
496. Circulating bilirubin levels and risk of colorectal cancer:serological and Mendelian randomization analyses
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Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Le Marchand, Loic, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín, Vicente, Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D.P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J.B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl Heinz, Freisling, Heinz, Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Le Marchand, Loic, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín, Vicente, Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D.P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J.B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl Heinz, and Freisling, Heinz
- Abstract
BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs64316
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- 2020
497. Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)
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Mahamat-Saleh, Yahya, Cervenka, Iris, Al-Rahmoun, Marie, Mancini, Francesca R., Severi, Gianluca, Ghiasvand, Reza, Veierod, Marit B., Caini, Saverio, Palli, Domenico, Botteri, Edoardo, Sacerdote, Carlotta, Ricceri, Fulvio, Trichopoulou, Antonia, Peppa, Eleni, La Vecchia, Carlo, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Tjønneland, Anne, Perez-Cornago, Aurora, Jakszyn, Paula, Grioni, Sara, Schulze, Matthias B., Skeie, Guri, Lasheras, Cristina, Colorado-Yohar, Sandra, Rodríguez-Barranco, Miguel, Kühn, Tilman, Katzke, Verena A., Amiano, Pilar, Tumino, Rosario, Panico, Salvatore, Ezponda, Ana, Sonestedt, Emily, Scalbert, Augustin, Weiderpass, Elisabete, Boutron-Ruault, Marie Christine, Kvaskoff, Marina, Mahamat-Saleh, Yahya, Cervenka, Iris, Al-Rahmoun, Marie, Mancini, Francesca R., Severi, Gianluca, Ghiasvand, Reza, Veierod, Marit B., Caini, Saverio, Palli, Domenico, Botteri, Edoardo, Sacerdote, Carlotta, Ricceri, Fulvio, Trichopoulou, Antonia, Peppa, Eleni, La Vecchia, Carlo, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Tjønneland, Anne, Perez-Cornago, Aurora, Jakszyn, Paula, Grioni, Sara, Schulze, Matthias B., Skeie, Guri, Lasheras, Cristina, Colorado-Yohar, Sandra, Rodríguez-Barranco, Miguel, Kühn, Tilman, Katzke, Verena A., Amiano, Pilar, Tumino, Rosario, Panico, Salvatore, Ezponda, Ana, Sonestedt, Emily, Scalbert, Augustin, Weiderpass, Elisabete, Boutron-Ruault, Marie Christine, and Kvaskoff, Marina
- Abstract
Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.
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- 2020
498. Exogenous hormone use and cutaneous melanoma risk in women:The European Prospective Investigation into Cancer and Nutrition
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Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnès, Boutron-Ruault, Marie Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjønneland, Anne, Olsen, Anja, Fortner, Renée T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sánchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, Kvaskoff, Marina, Cervenka, Iris, Al Rahmoun, Marie, Mahamat-Saleh, Yahya, Fournier, Agnès, Boutron-Ruault, Marie Christine, Severi, Gianluca, Caini, Saverio, Palli, Domenico, Ghiasvand, Reza, Veierod, Marit B., Botteri, Edoardo, Tjønneland, Anne, Olsen, Anja, Fortner, Renée T., Kaaks, Rudolf, Schulze, Matthias B., Panico, Salvatore, Trichopoulou, Antonia, Dessinioti, Clio, Niforou, Katerina, Sieri, Sabina, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Sandanger, Torkjel M., Colorado-Yohar, Sandra, Sánchez, Maria J., Gil Majuelo, Leire, Lujan-Barroso, Leila, Ardanaz, Eva, Merino, Susana, Isaksson, Karolin, Butt, Salma, Ljuslinder, Ingrid, Jansson, Malin, Travis, Ruth C., Khaw, Kay Tee, Weiderpass, Elisabete, Dossus, Laure, Rinaldi, Sabina, and Kvaskoff, Marina
- Abstract
Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
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- 2020
499. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
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MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Onderzoek Medische Oncologie, Aglago, Elom K., Huybrechts, Inge, Murphy, Neil, Casagrande, Corinne, Nicolas, Genevieve, Pischon, Tobias, Fedirko, Veronika, Severi, Gianluca, Boutron-Ruault, Marie Christine, Fournier, Agnès, Katzke, Verena, Kühn, Tilman, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Overvad, Kim, Lasheras, Cristina, Agudo, Antonio, Sánchez, Maria Jose, Amiano, Pilar, Huerta, José Maria, Ardanaz, Eva, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Bueno-de-Mesquita, Bas, May, Anne, Derksen, Jeroen W.G., Hellstrand, Sophie, Ohlsson, Bodil, Wennberg, Maria, Van Guelpen, Bethany, Skeie, Guri, Brustad, Magritt, Weiderpass, Elisabete, Cross, Amanda J., Ward, Heather, Riboli, Elio, Norat, Teresa, Chajes, Veronique, Gunter, Marc J., MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Onderzoek Medische Oncologie, Aglago, Elom K., Huybrechts, Inge, Murphy, Neil, Casagrande, Corinne, Nicolas, Genevieve, Pischon, Tobias, Fedirko, Veronika, Severi, Gianluca, Boutron-Ruault, Marie Christine, Fournier, Agnès, Katzke, Verena, Kühn, Tilman, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Overvad, Kim, Lasheras, Cristina, Agudo, Antonio, Sánchez, Maria Jose, Amiano, Pilar, Huerta, José Maria, Ardanaz, Eva, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Pala, Valeria, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Bueno-de-Mesquita, Bas, May, Anne, Derksen, Jeroen W.G., Hellstrand, Sophie, Ohlsson, Bodil, Wennberg, Maria, Van Guelpen, Bethany, Skeie, Guri, Brustad, Magritt, Weiderpass, Elisabete, Cross, Amanda J., Ward, Heather, Riboli, Elio, Norat, Teresa, Chajes, Veronique, and Gunter, Marc J.
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- 2020
500. Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
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MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Public Health Practice, Christakoudi, Sofia, Kakourou, Artemisia, Markozannes, Georgios, Tzoulaki, Ioanna, Weiderpass, Elisabete, Brennan, Paul, Gunter, Marc, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Madika, Anne-Laure, Severi, Gianluca, Katzke, Verena, Kühn, Tilman, Bergmann, Manuela M, Boeing, Heiner, Karakatsani, Anna, Martimianaki, Georgia, Thriskos, Paschalis, Masala, Giovanna, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Agudo, Antonio, Redondo-Sánchez, Daniel, Colorado-Yohar, Sandra M, Mokoroa, Olatz, Melander, Olle, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Bueno-de-Mesquita, Bas, van Gils, Carla H, Vermeulen, Roel C H, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Freisling, Heinz, Johansson, Mattias, Lennon, Hannah, Aune, Dagfinn, Riboli, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Tsilidis, Konstantinos K, MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Public Health Practice, Christakoudi, Sofia, Kakourou, Artemisia, Markozannes, Georgios, Tzoulaki, Ioanna, Weiderpass, Elisabete, Brennan, Paul, Gunter, Marc, Dahm, Christina C, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Madika, Anne-Laure, Severi, Gianluca, Katzke, Verena, Kühn, Tilman, Bergmann, Manuela M, Boeing, Heiner, Karakatsani, Anna, Martimianaki, Georgia, Thriskos, Paschalis, Masala, Giovanna, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Ricceri, Fulvio, Agudo, Antonio, Redondo-Sánchez, Daniel, Colorado-Yohar, Sandra M, Mokoroa, Olatz, Melander, Olle, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Bueno-de-Mesquita, Bas, van Gils, Carla H, Vermeulen, Roel C H, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Freisling, Heinz, Johansson, Mattias, Lennon, Hannah, Aune, Dagfinn, Riboli, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, and Tsilidis, Konstantinos K
- Published
- 2020
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