Scientific Reports (Oct 2022)
Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
- Giulia Peduzzi,
- Livia Archibugi,
- Verena Katzke,
- Manuel Gentiluomo,
- Gabriele Capurso,
- Anna Caterina Milanetto,
- Maria Gazouli,
- Mara Goetz,
- Hermann Brenner,
- Roel C. H. Vermeulen,
- Renata Talar-Wojnarowska,
- Giuseppe Vanella,
- Francesca Tavano,
- Maurizio Lucchesi,
- Beatrice Mohelnikova-Duchonova,
- Xuechen Chen,
- Vytautas Kiudelis,
- Péter Hegyi,
- Martin Oliverius,
- Hannah Stocker,
- Caterina Stornello,
- Ludmila Vodickova,
- Pavel Souček,
- John P. Neoptolemos,
- Sabrina Gloria Giulia Testoni,
- Luca Morelli,
- Rita T. Lawlor,
- Daniela Basso,
- Jakob R. Izbicki,
- Stefano Ermini,
- Juozas Kupcinskas,
- Raffaele Pezzilli,
- Ugo Boggi,
- Hanneke W. M. van Laarhoven,
- Andrea Szentesi,
- Bálint Erőss,
- Giovanni Capretti,
- Ben Schöttker,
- Jurgita Skieceviciene,
- Mateus Nóbrega Aoki,
- Casper H. J. van Eijck,
- Giulia Martina Cavestro,
- Federico Canzian,
- Daniele Campa
Affiliations
- Giulia Peduzzi
- Department of Biology, University of Pisa
- Livia Archibugi
- Digestive and Liver Disease Unit, Sant’Andrea Hospital
- Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
- Manuel Gentiluomo
- Department of Biology, University of Pisa
- Gabriele Capurso
- Digestive and Liver Disease Unit, Sant’Andrea Hospital
- Anna Caterina Milanetto
- Department DISCOG, University of Padova
- Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens
- Mara Goetz
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendorf
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Roel C. H. Vermeulen
- University of Utrecht
- Renata Talar-Wojnarowska
- Department of Digestive Tract Diseases, Medical University of Lodz
- Giuseppe Vanella
- Digestive and Liver Disease Unit, Sant’Andrea Hospital
- Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital
- Maurizio Lucchesi
- Oncology of Massa Carrara, Oncological Department, Azienda USL Toscana Nord Ovest
- Beatrice Mohelnikova-Duchonova
- Department of Oncology, Faculty of Medicine and Dentistry, Palacký University
- Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Vytautas Kiudelis
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences
- Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs
- Martin Oliverius
- Surgery Clinic Third Faculty of Medicine, Charles University
- Hannah Stocker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Caterina Stornello
- Digestive and Liver Disease Unit, Sant’Andrea Hospital
- Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences
- Pavel Souček
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University
- John P. Neoptolemos
- Department of General Surgery, University of Heidelberg
- Sabrina Gloria Giulia Testoni
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS
- Luca Morelli
- General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa
- Rita T. Lawlor
- ARC-NET, Centre for Applied Research on Cancer, University and Hospital Trust of Verona
- Daniela Basso
- Department DIMED-Laboratory Medicine, University of Padova
- Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendorf
- Stefano Ermini
- Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer
- Juozas Kupcinskas
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences
- Raffaele Pezzilli
- Potenza Medical County Association
- Ugo Boggi
- Division of General and Transplant Surgery, Pisa University Hospital
- Hanneke W. M. van Laarhoven
- Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam
- Andrea Szentesi
- Institute for Translational Medicine, Medical School, University of Pécs
- Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs
- Giovanni Capretti
- Department of Biomedical Sciences, Humanitas University
- Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Jurgita Skieceviciene
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences
- Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz)
- Casper H. J. van Eijck
- Department of Surgery, Erasmus MC University Medical Center
- Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
- Daniele Campa
- Department of Biology, University of Pisa
- DOI
- https://doi.org/10.1038/s41598-022-22973-9
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 8
Abstract
Abstract The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10−5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk.
