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
(2022) Scientific Reports, volume 12
(Article)
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
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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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Keywords: Female, Humans, Adenocarcinoma/pathology, Carcinoma, Pancreatic Ductal/pathology, Estrogens/genetics, Pancreatic Neoplasms/epidemiology, Pregnenolone, General
ISSN: 2045-2322
Publisher: NLM (Medline)
Note: Funding Information: The research used the genotyping data provided by the EPIC, we would like to thank the contributors from the UK. The EPIC-Norfolk study ( https://doi.org/10.22025/2019.10.105.00004 ) has received funding from the Medical Research Council [MR/N003284/1 and MC-UU_12015/1] and Cancer Research UK [C864/A14136]. We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. This work was supported by intramural funding of DKFZ (Federico Canzian), by Fondazione Tizzi ( www.fondazionetizzi.it ) and by Fondazione Arpa ( www.fondazionearpa.it ) (Daniele Campa), by the Czech Health Research Council, project no.: NV19-03-00097 (Beatrice Mohelnikova-Duchonova), by AZV, NU21-07-00247 and Operational Programme Integrated Infrastructure for the project: Integrative strategy in development of personalized medicine of selected malignant tumours and its impact on quality of life, IMTS: 313011V446, co-financed by the European Regional Development Fund (Ludmila Vodickova), by National operation Programm: National Institute for cancer research LX22NPO05102 (Ludmila Vodickova). The research leading to these results has received funding from AIRC under IG 2021-ID. 26201 project-P.I. Gabriele Capurso. This work was supported by Italian Ministry of Health grants (Ricerca Corrente 2022–2024) to Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo (FG), Italy and by the “5x1000” voluntary contribution. Funding Information: The research used the genotyping data provided by the EPIC, we would like to thank the contributors from the UK. The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council [MR/N003284/1 and MC-UU_12015/1] and Cancer Research UK [C864/A14136]. We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. This work was supported by intramural funding of DKFZ (Federico Canzian), by Fondazione Tizzi (www.fondazionetizzi.it) and by Fondazione Arpa (www.fondazionearpa.it) (Daniele Campa), by the Czech Health Research Council, project no.: NV19-03-00097 (Beatrice Mohelnikova-Duchonova), by AZV, NU21-07-00247 and Operational Programme Integrated Infrastructure for the project: Integrative strategy in development of personalized medicine of selected malignant tumours and its impact on quality of life, IMTS: 313011V446, co-financed by the European Regional Development Fund (Ludmila Vodickova), by National operation Programm: National Institute for cancer research LX22NPO05102 (Ludmila Vodickova). The research leading to these results has received funding from AIRC under IG 2021-ID. 26201 project-P.I. Gabriele Capurso. This work was supported by Italian Ministry of Health grants (Ricerca Corrente 2022–2024) to Fondazione “Casa Sollievo della Sofferenza” IRCCS Hospital, San Giovanni Rotondo (FG), Italy and by the “5x1000” voluntary contribution. Publisher Copyright: © 2022, The Author(s).
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