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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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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 |
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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 |
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