Publications

Authors:

Gálvez-Montosa, Fernando; Peduzzi, Giulia; Sanchez-Maldonado, José Manuel; Ter Horst, Rob; Cabrera-Serrano, Antonio J; Gentiluomo, Manuel; Macauda, Angelica; Luque, Natalia; Ünal, Pelin; García-Verdejo, Francisco Javier; Li, Yang; López López, José Antonio; Stein, Angelika; Bueno-de-Mesquita, H Bas; Arcidiacono, Paolo Giorgio; Zanette, Dalila Luciola; Kahlert, Christoph; Perri, Francesco; Soucek, Pavel; Talar-Wojnarowska, Renata; Theodoropoulos, George E; Izbicki, Jakob R; Tamás, Hussein; Van Laarhoven, Hanneke; Nappo, Gennaro; Petrone, Maria Chiara; Lovecek, Martin; Vermeulen, Roel C H; Adamonis, Kestutis; Reyes-Zurita, Fernando Jesus; Holleczek, Bernd; Sumskiene, Jolanta; Mohelníková-Duchoňová, Beatrice; Lawlor, Rita T; Pezzilli, Raffaele; Aoki, Mateus Nobrega; Pasquali, Claudio; Petrenkiene, Vitalija; Basso, Daniela; Bunduc, Stefania; Comandatore, Annalisa; Brenner, Hermann; Ermini, Stefano; Vanella, Giuseppe; Goetz, Mara R; Archibugi, Livia; Lucchesi, Maurizio; Uzunoglu, Faik Guntac; Busch, Olivier; Milanetto, Anna Caterina; Puzzono, Marta; Kupcinskas, Juozas; Morelli, Luca; Sperti, Cosimo; Carrara, Silvia; Capurso, Gabriele; van Eijck, Casper H J; Oliverius, Martin; Roth, Susanne; Tavano, Francesca; Kaaks, Rudolf; Szentesi, Andrea; Vodickova, Ludmila; Luchini, Claudio; Schöttker, Ben; Landi, Stefano; Dohan, Orsolya; Tacelli, Matteo; Greenhalf, William; Gazouli, Maria; Neoptolemos, John P; Cavestro, Giulia Martina; Boggi, Ugo; Latiano, Anna; Hegyi, Péter; Ginocchi, Laura; Netea, Mihai G; Sánchez-Rovira, Pedro; Canzian, Federico; Campa, Daniele; Sainz, Juan

Title:

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

International Journal of Cancer

ISSN of journal:

0020-7136

N° Volume:

156

Number or Folder:

2

Page numbers:

339-352

Keyword:

autophagy; functional characterization; genetic variants; pancreatic cancer; polymorphisms; susceptibility

Short description of contents:

: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Note:

Epub 2024 Sep 25

Product ID:

141252

Handle IRIS:

11562/1138386

Last Modified:

November 29, 2024

Bibliographic citation:

Gálvez-Montosa, Fernando; Peduzzi, Giulia; Sanchez-Maldonado, José Manuel; Ter Horst, Rob; Cabrera-Serrano, Antonio J; Gentiluomo, Manuel; Macauda, Angelica; Luque, Natalia; Ünal, Pelin; García-Verdejo, Francisco Javier; Li, Yang; López López, José Antonio; Stein, Angelika; Bueno-de-Mesquita, H Bas; Arcidiacono, Paolo Giorgio; Zanette, Dalila Luciola; Kahlert, Christoph; Perri, Francesco; Soucek, Pavel; Talar-Wojnarowska, Renata; Theodoropoulos, George E; Izbicki, Jakob R; Tamás, Hussein; Van Laarhoven, Hanneke; Nappo, Gennaro; Petrone, Maria Chiara; Lovecek, Martin; Vermeulen, Roel C H; Adamonis, Kestutis; Reyes-Zurita, Fernando Jesus; Holleczek, Bernd; Sumskiene, Jolanta; Mohelníková-Duchoňová, Beatrice; Lawlor, Rita T; Pezzilli, Raffaele; Aoki, Mateus Nobrega; Pasquali, Claudio; Petrenkiene, Vitalija; Basso, Daniela; Bunduc, Stefania; Comandatore, Annalisa; Brenner, Hermann; Ermini, Stefano; Vanella, Giuseppe; Goetz, Mara R; Archibugi, Livia; Lucchesi, Maurizio; Uzunoglu, Faik Guntac; Busch, Olivier; Milanetto, Anna Caterina; Puzzono, Marta; Kupcinskas, Juozas; Morelli, Luca; Sperti, Cosimo; Carrara, Silvia; Capurso, Gabriele; van Eijck, Casper H J; Oliverius, Martin; Roth, Susanne; Tavano, Francesca; Kaaks, Rudolf; Szentesi, Andrea; Vodickova, Ludmila; Luchini, Claudio; Schöttker, Ben; Landi, Stefano; Dohan, Orsolya; Tacelli, Matteo; Greenhalf, William; Gazouli, Maria; Neoptolemos, John P; Cavestro, Giulia Martina; Boggi, Ugo; Latiano, Anna; Hegyi, Péter; Ginocchi, Laura; Netea, Mihai G; Sánchez-Rovira, Pedro; Canzian, Federico; Campa, Daniele; Sainz, Juan, Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization «International Journal of Cancer» , vol. 156 , n. 2 , 2025 , pp. 339-352

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo