Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed...

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Main Authors: Corradi, Chiara (Author) , Lencioni, Giulia (Author) , Felici, Alessio (Author) , Rizzato, Cosmeri (Author) , Gentiluomo, Manuel (Author) , Ermini, Stefano (Author) , Archibugi, Livia (Author) , Mickevicius, Antanas (Author) , Lucchesi, Maurizio (Author) , Malecka-Wojciesko, Ewa (Author) , Basso, Daniela (Author) , Arcidiacono, Paolo Giorgio (Author) , Petrone, Maria Chiara (Author) , Carrara, Silvia (Author) , Götz, Mara (Author) , Bunduc, Stefania (Author) , Holleczek, Bernd (Author) , Aoki, Mateus Nóbrega (Author) , Uzunoglu, Faik G. (Author) , Zanette, Dalila Lucíola (Author) , Mambrini, Andrea (Author) , Jamroziak, Krzysztof (Author) , Oliverius, Martin (Author) , Lovecek, Martin (Author) , Cavestro, Giulia Martina (Author) , Milanetto, Anna Caterina (Author) , Peduzzi, Giulia (Author) , Duchonova, Beatrice Mohelnikova (Author) , Izbicki, Jakob R. (Author) , Zalinkevicius, Rimantas (Author) , Hlavac, Viktor (Author) , van Eijck, Casper H. J. (Author) , Brenner, Hermann (Author) , Vanella, Giuseppe (Author) , Vokacova, Klara (Author) , Soucek, Pavel (Author) , Tavano, Francesca (Author) , Perri, Francesco (Author) , Capurso, Gabriele (Author) , Hussein, Tamás (Author) , Kiudelis, Mindaugas (Author) , Kupcinskas, Juozas (Author) , Busch, Olivier R. (Author) , Morelli, Luca (Author) , Theodoropoulos, George E. (Author) , Testoni, Sabrina Gloria Giulia (Author) , Adamonis, Kestutis (Author) , Neoptolemos, John P. (Author) , Gazouli, Maria (Author) , Pasquali, Claudio (Author) , Kormos, Zita (Author) , Skalicky, Pavel (Author) , Pezzilli, Raffaele (Author) , Sperti, Cosimo (Author) , Kauffmann, Emanuele (Author) , Büchler, Markus W. (Author) , Schöttker, Ben (Author) , Hegyi, Péter (Author) , Capretti, Giovanni (Author) , Lawlor, Rita T. (Author) , Canzian, Federico (Author) , Campa, Daniele (Author)
Format: Article (Journal)
Language:English
Published: 26 June 2024
In: International journal of cancer
Year: 2024, Volume: 155, Issue: 8, Pages: 1432-1442
ISSN:1097-0215
DOI:10.1002/ijc.35046
Online Access:lizenzpflichtig
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Author Notes:Chiara Corradi, Giulia Lencioni, Alessio Felici, Cosmeri Rizzato, Manuel Gentiluomo, Stefano Ermini, Livia Archibugi, Antanas Mickevicius, Maurizio Lucchesi, Ewa Malecka-Wojciesko, Daniela Basso, Paolo Giorgio Arcidiacono, Maria Chiara Petrone, Silvia Carrara, Mara Götz, Stefania Bunduc, Bernd Holleczek, Mateus Nóbrega Aoki, Faik G. Uzunoglu, Dalila Lucíola Zanette, Andrea Mambrini, Krzysztof Jamroziak, Martin Oliverius, Martin Lovecek, Giulia Martina Cavestro, Anna Caterina Milanetto, Giulia Peduzzi, Beatrice Mohelnikova Duchonova, Jakob R. Izbicki, Rimantas Zalinkevicius, Viktor Hlavac, Casper H.J. van Eijck, Hermann Brenner, Giuseppe Vanella, Klara Vokacova, Pavel Soucek, Francesca Tavano, Francesco Perri, Gabriele Capurso, Tamás Hussein, Mindaugas Kiudelis, Juozas Kupcinskas, Olivier R. Busch, Luca Morelli, George E. Theodoropoulos, Sabrina Gloria Giulia Testoni, Kestutis Adamonis, John P. Neoptolemos, Maria Gazouli, Claudio Pasquali, Zita Kormos, Pavel Skalicky, Raffaele Pezzilli, Cosimo Sperti, Emanuele Kauffmann, Markus W. Büchler, Ben Schöttker, Péter Hegyi, Giovanni Capretti, Rita T. Lawlor, Federico Canzian, Daniele Campa
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Summary:Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.
Item Description:Gesehen am 04.03.2025
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.35046