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...

Descripción completa

Detalles Bibliográficos
Autores principales: Peduzzi, Giulia, Archibugi, Livia, Katzke, Verena, Gentiluomo, Manuel, Capurso, Gabriele, Milanetto, Anna Caterina, Gazouli, Maria, Goetz, Mara, Brenner, Hermann, Vermeulen, Roel C. H., Talar-Wojnarowska, Renata, Vanella, Giuseppe, Tavano, Francesca, Lucchesi, Maurizio, Mohelnikova-Duchonova, Beatrice, Chen, Xuechen, Kiudelis, Vytautas, Hegyi, Péter, Oliverius, Martin, Stocker, Hannah, Stornello, Caterina, Vodickova, Ludmila, Souček, Pavel, Neoptolemos, John P., Testoni, Sabrina Gloria Giulia, Morelli, Luca, Lawlor, Rita T., Basso, Daniela, Izbicki, Jakob R., Ermini, Stefano, Kupcinskas, Juozas, Pezzilli, Raffaele, Boggi, Ugo, van Laarhoven, Hanneke W. M., Szentesi, Andrea, Erőss, Bálint, Capretti, Giovanni, Schöttker, Ben, Skieceviciene, Jurgita, Aoki, Mateus Nóbrega, van Eijck, Casper H. J., Cavestro, Giulia Martina, Canzian, Federico, Campa, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613634/
https://www.ncbi.nlm.nih.gov/pubmed/36302831
http://dx.doi.org/10.1038/s41598-022-22973-9
_version_ 1784820018675974144
author Peduzzi, Giulia
Archibugi, Livia
Katzke, Verena
Gentiluomo, Manuel
Capurso, Gabriele
Milanetto, Anna Caterina
Gazouli, Maria
Goetz, Mara
Brenner, Hermann
Vermeulen, Roel C. H.
Talar-Wojnarowska, Renata
Vanella, Giuseppe
Tavano, Francesca
Lucchesi, Maurizio
Mohelnikova-Duchonova, Beatrice
Chen, Xuechen
Kiudelis, Vytautas
Hegyi, Péter
Oliverius, Martin
Stocker, Hannah
Stornello, Caterina
Vodickova, Ludmila
Souček, Pavel
Neoptolemos, John P.
Testoni, Sabrina Gloria Giulia
Morelli, Luca
Lawlor, Rita T.
Basso, Daniela
Izbicki, Jakob R.
Ermini, Stefano
Kupcinskas, Juozas
Pezzilli, Raffaele
Boggi, Ugo
van Laarhoven, Hanneke W. M.
Szentesi, Andrea
Erőss, Bálint
Capretti, Giovanni
Schöttker, Ben
Skieceviciene, Jurgita
Aoki, Mateus Nóbrega
van Eijck, Casper H. J.
Cavestro, Giulia Martina
Canzian, Federico
Campa, Daniele
author_facet Peduzzi, Giulia
Archibugi, Livia
Katzke, Verena
Gentiluomo, Manuel
Capurso, Gabriele
Milanetto, Anna Caterina
Gazouli, Maria
Goetz, Mara
Brenner, Hermann
Vermeulen, Roel C. H.
Talar-Wojnarowska, Renata
Vanella, Giuseppe
Tavano, Francesca
Lucchesi, Maurizio
Mohelnikova-Duchonova, Beatrice
Chen, Xuechen
Kiudelis, Vytautas
Hegyi, Péter
Oliverius, Martin
Stocker, Hannah
Stornello, Caterina
Vodickova, Ludmila
Souček, Pavel
Neoptolemos, John P.
Testoni, Sabrina Gloria Giulia
Morelli, Luca
Lawlor, Rita T.
Basso, Daniela
Izbicki, Jakob R.
Ermini, Stefano
Kupcinskas, Juozas
Pezzilli, Raffaele
Boggi, Ugo
van Laarhoven, Hanneke W. M.
Szentesi, Andrea
Erőss, Bálint
Capretti, Giovanni
Schöttker, Ben
Skieceviciene, Jurgita
Aoki, Mateus Nóbrega
van Eijck, Casper H. J.
Cavestro, Giulia Martina
Canzian, Federico
Campa, Daniele
author_sort Peduzzi, Giulia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9613634
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-96136342022-10-29 Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women Peduzzi, Giulia Archibugi, Livia Katzke, Verena Gentiluomo, Manuel Capurso, Gabriele Milanetto, Anna Caterina Gazouli, Maria Goetz, Mara Brenner, Hermann Vermeulen, Roel C. H. Talar-Wojnarowska, Renata Vanella, Giuseppe Tavano, Francesca Lucchesi, Maurizio Mohelnikova-Duchonova, Beatrice Chen, Xuechen Kiudelis, Vytautas Hegyi, Péter Oliverius, Martin Stocker, Hannah Stornello, Caterina Vodickova, Ludmila Souček, Pavel Neoptolemos, John P. Testoni, Sabrina Gloria Giulia Morelli, Luca Lawlor, Rita T. Basso, Daniela Izbicki, Jakob R. Ermini, Stefano Kupcinskas, Juozas Pezzilli, Raffaele Boggi, Ugo van Laarhoven, Hanneke W. M. Szentesi, Andrea Erőss, Bálint Capretti, Giovanni Schöttker, Ben Skieceviciene, Jurgita Aoki, Mateus Nóbrega van Eijck, Casper H. J. Cavestro, Giulia Martina Canzian, Federico Campa, Daniele Sci Rep Article 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. Nature Publishing Group UK 2022-10-27 /pmc/articles/PMC9613634/ /pubmed/36302831 http://dx.doi.org/10.1038/s41598-022-22973-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Peduzzi, Giulia
Archibugi, Livia
Katzke, Verena
Gentiluomo, Manuel
Capurso, Gabriele
Milanetto, Anna Caterina
Gazouli, Maria
Goetz, Mara
Brenner, Hermann
Vermeulen, Roel C. H.
Talar-Wojnarowska, Renata
Vanella, Giuseppe
Tavano, Francesca
Lucchesi, Maurizio
Mohelnikova-Duchonova, Beatrice
Chen, Xuechen
Kiudelis, Vytautas
Hegyi, Péter
Oliverius, Martin
Stocker, Hannah
Stornello, Caterina
Vodickova, Ludmila
Souček, Pavel
Neoptolemos, John P.
Testoni, Sabrina Gloria Giulia
Morelli, Luca
Lawlor, Rita T.
Basso, Daniela
Izbicki, Jakob R.
Ermini, Stefano
Kupcinskas, Juozas
Pezzilli, Raffaele
Boggi, Ugo
van Laarhoven, Hanneke W. M.
Szentesi, Andrea
Erőss, Bálint
Capretti, Giovanni
Schöttker, Ben
Skieceviciene, Jurgita
Aoki, Mateus Nóbrega
van Eijck, Casper H. J.
Cavestro, Giulia Martina
Canzian, Federico
Campa, Daniele
Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title_full Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title_fullStr Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title_full_unstemmed Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title_short Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
title_sort common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613634/
https://www.ncbi.nlm.nih.gov/pubmed/36302831
http://dx.doi.org/10.1038/s41598-022-22973-9
work_keys_str_mv AT peduzzigiulia commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT archibugilivia commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT katzkeverena commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT gentiluomomanuel commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT capursogabriele commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT milanettoannacaterina commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT gazoulimaria commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT goetzmara commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT brennerhermann commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT vermeulenroelch commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT talarwojnarowskarenata commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT vanellagiuseppe commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT tavanofrancesca commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT lucchesimaurizio commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT mohelnikovaduchonovabeatrice commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT chenxuechen commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT kiudelisvytautas commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT hegyipeter commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT oliveriusmartin commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT stockerhannah commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT stornellocaterina commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT vodickovaludmila commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT soucekpavel commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT neoptolemosjohnp commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT testonisabrinagloriagiulia commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT morelliluca commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT lawlorritat commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT bassodaniela commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT izbickijakobr commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT erministefano commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT kupcinskasjuozas commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT pezzilliraffaele commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT boggiugo commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT vanlaarhovenhannekewm commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT szentesiandrea commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT erossbalint commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT caprettigiovanni commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT schottkerben commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT skiecevicienejurgita commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT aokimateusnobrega commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT vaneijckcasperhj commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT cavestrogiuliamartina commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT canzianfederico commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen
AT campadaniele commonvariabilityinoestrogenrelatedgenesandpancreaticductaladenocarcinomariskinwomen