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Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

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 asso...

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Main Authors: Peduzzi, Giulia (Author) , Archibugi, Livia (Author) , Katzke, Verena (Author) , Gentiluomo, Manuel (Author) , Capurso, Gabriele (Author) , Milanetto, Anna Caterina (Author) , Gazouli, Maria (Author) , Goetz, Mara (Author) , Brenner, Hermann (Author) , Vermeulen, Roel C. H. (Author) , Talar-Wojnarowska, Renata (Author) , Vanella, Giuseppe (Author) , Tavano, Francesca (Author) , Lucchesi, Maurizio (Author) , Mohelnikova-Duchonova, Beatrice (Author) , Chen, Xuechen (Author) , Kiudelis, Vytautas (Author) , Hegyi, Péter (Author) , Oliverius, Martin (Author) , Stocker, Hannah (Author) , Stornello, Caterina (Author) , Vodickova, Ludmila (Author) , Souček, Pavel (Author) , Neoptolemos, John P. (Author) , Testoni, Sabrina Gloria Giulia (Author) , Morelli, Luca (Author) , Lawlor, Rita T. (Author) , Basso, Daniela (Author) , Izbicki, Jakob R. (Author) , Ermini, Stefano (Author) , Kupcinskas, Juozas (Author) , Pezzilli, Raffaele (Author) , Boggi, Ugo (Author) , van Laarhoven, Hanneke W. M. (Author) , Szentesi, Andrea (Author) , Erőss, Bálint (Author) , Capretti, Giovanni (Author) , Schöttker, Ben (Author) , Skieceviciene, Jurgita (Author) , Aoki, Mateus Nóbrega (Author) , van Eijck, Casper H. J. (Author) , Cavestro, Giulia Martina (Author) , Canzian, Federico (Author) , Campa, Daniele (Author)
Format: Article (Journal)
Language:English
Published: 27 October 2022
In: Scientific reports
Year: 2022, Volume: 12, Pages: 1-8
ISSN:2045-2322
DOI:10.1038/s41598-022-22973-9
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-022-22973-9
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-022-22973-9
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Author Notes: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

MARC

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245 1 0 |a Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women  |c 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 
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520 |a 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. 
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