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

Sep 21, 2026

Pancreatic ductal adenocarcinoma remains highly lethal, often diagnosed at unresectable or metastatic stages with limited survival. This study evaluates whether single nucleotide polymorphisms across 234 autophagy-related genes affect disease risk using three large European cohorts comprising 12,754 PDAC cases and 324,926 controls. The meta-analysis highlights BIDrs9604789 as a risk-associated variant and confirms TP63rs1515496 and TP63rs35389543 associations. Functional and immunologic findings link TP63 variants to altered regulatory T-cell subsets, supporting transcription-factor mediated mechanisms and identifying BID and TP63 in PDAC susceptibility.

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CategoryHealthcare

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DOI: 10.1002/ijc.35196 RES EARCH A RTICLE C a ncer Geneti cs an d E p igen e ti cs Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A metaanalysis of three large European cohorts and functional characterization Fernando Gálvez-Montosa 1 | Giulia Peduzzi 2 | José Manuel Sanchez-Maldonado 3,4,5,6 | Rob ter Horst 7,8 | Antonio J. Cabrera-Serrano 4,5 | Manuel Gentiluomo 2 | Angelica Macauda 6 | Natalia Luque 1 | Pelin Ünal 6 | Francisco José García-Verdejo 1 | Yang Li 7,8 | José Antonio López López 1 | Angelika Stein 6 | H. Bas Bueno-de-Mesquita 9† | Paolo Giorgio Arcidiacono 10 | Dalila Luciola Zanette 11 | Christoph Kahlert 12 | Francesco Perri 13 | Pavel Soucek 14 | Renata Talar-Wojnarowska 15 | George E. Theodoropoulos 16 | Jakob R. Izbicki 17 | Hussein Tamás 18,19 | Hanneke Van Laarhoven 20,21 | Gennaro Nappo 22,23 | Maria Chiara Petrone 10 | Martin Lovecek 24 | Roel C. H. Vermeulen 25 | Kestutis Adamonis 26 | Fernando Jesus Reyes-Zurita 3 | Bernd Holleczek 27,28 | Jolanta Sumskiene 26 | Beatrice Mohelníková-Ducho ová 29 | Rita T. Lawlor 30,31 | Raffaele Pezzilli 32 | Mateus Nobrega Aoki 11 | Claudio Pasquali 33 | Vitalija Petrenkiene 26 | Daniela Basso 34 | Stefania Bunduc 18,19,35,36 | Annalisa Comandatore 37 | Hermann Brenner 28,38 | Stefano Ermini 2 | Giuseppe Vanella 39,40 | Mara R. Goetz 17 | Livia Archibugi 39,40 | Maurizio Lucchesi 41 | Faik Guntac Uzunoglu 17 | Olivier Busch 21,42 | Anna Caterina Milanetto 33 | Marta Puzzono 43 | Juozas Kupcinskas 26 | Luca Morelli 37 | Cosimo Sperti 33 | Silvia Carrara 44 | Gabriele Capurso 39,40 | Casper H. J. van Eijck 45 | Martin Oliverius 46 | Susanne Roth 12 | Francesca Tavano 13 | Rudolf Kaaks 47 | Andrea Szentesi 48 | Ludmila Vodickova 49,50,51 | Claudio Luchini 30,52 | Ben Schöttker 28 | Stefano Landi 2 | Orsolya Dohan 19 | Matteo Tacelli 10 | Fernando Gálvez-Montosa, Giulia Peduzzi, and José Manuel Sanchez-Maldonado share first authorship. Daniele Campa and Juan Sainz share last authorship. † Deceased researcher. For affiliations refer to page 348 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s) . International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. William Greenhalf 53 | Maria Gazouli 54 | John P. Neoptolemos 12 | Giulia Martina Cavestro 43 | Ugo Boggi 55 | Anna Latiano 13 | Péter Hegyi 18,19,48,56 | Laura Ginocchi 41 | Mihai G. Netea 57,58 | Pedro Sánchez-Rovira 1 | Federico Canzian 6 | Daniele Campa 2 | Juan Sainz 3,4,5,59 Correspondence Juan Sainz, Department of Biochemistry and Molecular Biology I, University of Granada, Avenida Fuente Nueva, s/n, 18071, Granada, Spain. Email: [jsainz@ugr.es](jsainz@ugr.es) Funding information Czech Republic Ministry of Health, Grant/Award Number: GACR21-27902 and AZVNU21-03-00145; “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo; Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER, Grant/Award Number: PY20/01282; Instituto de Salud Carlos III, Grant/Award Numbers: PI17/02256, PI20/01845; Associazione Italiana Ricerca Cancro, Grant/Award Number: 26343; National Institute for Cancer Research (Programme EXCELES), Grant/Award Number: LX22NPO5102; Charles University, Project GA UK No. 120, Grant/Award Number: UNCE/MED/006 [Correction added on 07 November 2024, after first online publication: The name of the author “Francisco José García-Verdejo” has been corrected.] Abstract 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

FAQs

What was the main goal of this study on autophagy-related genes and pancreatic cancer?

To determine whether single nucleotide polymorphisms in autophagy-related genes influence the risk of developing pancreatic ductal adenocarcinoma.

Which genetic variants were identified as associated with PDAC risk?

The meta-analysis identified BIDrs9604789 as increasing PDAC risk and confirmed associations for TP63rs1515496 and TP63rs35389543.

How did the study connect TP63 variants to potential biological mechanisms?

It reported changes in regulatory T-cell subsets in carriers of the TP63rs1515496G allele and discussed transcription-factor binding-site alterations involving FOXA1 and CTCF.

Sep 21, 2026

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