E Molina-Montes1, P Gomez-Rubio1, M Márquez1, M Rava1, M Löhr2, C W Michalski3,4, X Molero5, A Farré6, J Perea7, W Greenhalf8, L Ilzarbe9, M O'Rorke10, A Tardón11, T Gress12, V M Barberà13, T Crnogorac-Jurcevic14, E Domínguez-Muñoz15, L Muñoz-Bellvís16, J Balsells5, E Costello8, J Huang2, M Iglesias9, J Kleeff3,17, Bo Kong3, J Mora6, L Murray10, D O'Driscoll18, I Poves9, A Scarpa19, W Ye2, M Hidalgo20, L Sharp18,21, A Carrato22, F X Real23, N Malats1. 1. Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group, Madrid, and CIBERONC, Spain. 2. Karolinska Institutet and University Hospital, Gastrocentrum, Stockholm, Sweden. 3. Technical University of Munich, Department of Surgery, Munich, Germany. 4. University of Heidelberg, Department of Surgery, Heidelberg, Germany. 5. Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, and CIBEREHD, Spain. 6. Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology, Barcelona, Spain. 7. University Hospital 12 de Octubre, Department of Surgery, Madrid, Spain. 8. Royal Liverpool University Hospital, Department of Molecular and Clinical Cancer Medicine, Liverpool, UK. 9. Hospital del Mar-Parc de Salut Mar, Barcelona, Spain. 10. Queen's University Belfast, Centre for Public Health, Belfast, UK. 11. Instituto Universitario de Oncología del Principado de Asturias, Department of Medicine, Oviedo, and CIBERESP, Spain. 12. University Hospital of Giessen and Marburg, Department of Gastroenterology, Marburg, Germany. 13. General University Hospital of Elche, Molecular Genetics Laboratory, Elche, Spain. 14. Barts Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, London, UK. 15. University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology, Santiago de Compostela, Spain. 16. Salamanca University Hospital, General and Digestive Surgery Department, Salamanca, Spain. 17. Martin-Luther-University Halle-Wittenberg, Department of Visceral, Vascular and Endocrine Surgery, Halle (Saale), Germany. 18. National Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland. 19. ARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy. 20. Madrid-Norte-Sanchinarro Hospital, Madrid, Spain. 21. Newcastle University, Institute of Health and Society, Newcastle upon Tyne, UK. 22. Ramón y Cajal University Hospital, Department of Oncology, IRYCIS, Alcala University, Madrid, and CIBERONC, Spain. 23. Spanish National Cancer Research Centre (CNIO), Epithelial Carcinogenesis Group, Madrid, Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, Barcelona, and CIBERONC, Spain.
Abstract
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.
Authors: Divyanshoo R Kohli; Ken Robert Smith; Jathine Wong; Zhe Yu; Kenneth Boucher; Douglas O Faigel; Rahul Pannala; Randall W Burt; Karen Curtin; N Jewel Samadder Journal: J Gastroenterol Date: 2019-06-25 Impact factor: 7.527
Authors: Patrick Michl; Matthias Löhr; John P Neoptolemos; Gabriele Capurso; Vinciane Rebours; Nuria Malats; Mathilde Ollivier; Luigi Ricciardiello Journal: United European Gastroenterol J Date: 2021-08-25 Impact factor: 6.866
Authors: Evangelina López de Maturana; Juan Antonio Rodríguez; Lola Alonso; Oscar Lao; Esther Molina-Montes; Isabel Adoración Martín-Antoniano; Paulina Gómez-Rubio; Rita Lawlor; Alfredo Carrato; Manuel Hidalgo; Mar Iglesias; Xavier Molero; Matthias Löhr; Christopher Michalski; José Perea; Michael O'Rorke; Victor Manuel Barberà; Adonina Tardón; Antoni Farré; Luís Muñoz-Bellvís; Tanja Crnogorac-Jurcevic; Enrique Domínguez-Muñoz; Thomas Gress; William Greenhalf; Linda Sharp; Luís Arnes; Lluís Cecchini; Joaquim Balsells; Eithne Costello; Lucas Ilzarbe; Jörg Kleeff; Bo Kong; Mirari Márquez; Josefina Mora; Damian O'Driscoll; Aldo Scarpa; Weimin Ye; Jingru Yu; Montserrat García-Closas; Manolis Kogevinas; Nathaniel Rothman; Debra T Silverman; Demetrius Albanes; Alan A Arslan; Laura Beane-Freeman; Paige M Bracci; Paul Brennan; Bas Bueno-de-Mesquita; Julie Buring; Federico Canzian; Margaret Du; Steve Gallinger; J Michael Gaziano; Phyllis J Goodman; Marc Gunter; Loic LeMarchand; Donghui Li; Rachael E Neale; Ulrika Peters; Gloria M Petersen; Harvey A Risch; Maria José Sánchez; Xiao-Ou Shu; Mark D Thornquist; Kala Visvanathan; Wei Zheng; Stephen J Chanock; Douglas Easton; Brian M Wolpin; Rachael Z Stolzenberg-Solomon; Alison P Klein; Laufey T Amundadottir; Marc A Marti-Renom; Francisco X Real; Núria Malats Journal: Genome Med Date: 2021-02-01 Impact factor: 11.117
Authors: Linda Kachuri; Rebecca E Graff; Karl Smith-Byrne; Travis J Meyers; Sara R Rashkin; Elad Ziv; John S Witte; Mattias Johansson Journal: Nat Commun Date: 2020-11-27 Impact factor: 14.919