Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

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 Goetz; Stefania Bunduc; Bernd Holleczek; Mateus Nobrega Aoki; Faik G. Uzunoglu; Dalila Luciola 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; Tamas 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. Buechler; Ben Schoettker; Peter Hegyi; Giovanni Capretti; Rita T. Lawlor; Federico Canzian; Daniele Campa

doi:10.1002/ijc.35046

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

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 Goetz, Stefania Bunduc, Bernd Holleczek, Mateus Nobrega Aoki, Faik G. Uzunoglu, Dalila Luciola ZanetteAndrea 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, Tamas 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. Buechler, Ben Schoettker, Peter Hegyi, Giovanni Capretti, Rita T. Lawlor, Federico Canzian, Daniele Campa^*

^*Corresponding author for this work

Pulmonary Medicine

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1432-1442
Number of pages	11
Journal	International Journal of Cancer
Volume	155
Issue number	8
Early online date	26 Jun 2024
DOIs	https://doi.org/10.1002/ijc.35046
Publication status	Published - 15 Oct 2024

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Publisher Copyright:
© 2024 UICC.

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10.1002/ijc.35046

Intl Journal of Cancer - 2024 - Corradi - Potential association between PSCA rs2976395 functional variant and pancreaticFinal published version, 982 KBLicence: Article 25fa Dutch Copyright Act

Cite this

Corradi, C., Lencioni, G., Felici, A., Rizzato, C., Gentiluomo, M., Ermini, S., Archibugi, L., Mickevicius, A., Lucchesi, M., Malecka-Wojciesko, E., Basso, D., Arcidiacono, P. G., Petrone, M. C., Carrara, S., Goetz, M., Bunduc, S., Holleczek, B., Aoki, M. N., Uzunoglu, F. G., ... Campa, D. (2024). Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk. International Journal of Cancer, 155(8), 1432-1442. https://doi.org/10.1002/ijc.35046

@article{9d5cdef599684389a4e0a83b74114baa,

title = "Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk",

abstract = "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.",

author = "Chiara Corradi and Giulia Lencioni and Alessio Felici and Cosmeri Rizzato and Manuel Gentiluomo and Stefano Ermini and Livia Archibugi and Antanas Mickevicius and Maurizio Lucchesi and Ewa Malecka-Wojciesko and Daniela Basso and Arcidiacono, {Paolo Giorgio} and Petrone, {Maria Chiara} and Silvia Carrara and Mara Goetz and Stefania Bunduc and Bernd Holleczek and Aoki, {Mateus Nobrega} and Uzunoglu, {Faik G.} and Zanette, {Dalila Luciola} and Andrea Mambrini and Krzysztof Jamroziak and Martin Oliverius and Martin Lovecek and Cavestro, {Giulia Martina} and Milanetto, {Anna Caterina} and Giulia Peduzzi and Duchonova, {Beatrice Mohelnikova} and Izbicki, {Jakob R.} and Rimantas Zalinkevicius and Viktor Hlavac and {van Eijck}, {Casper H. J.} and Hermann Brenner and Giuseppe Vanella and Klara Vokacova and Pavel Soucek and Francesca Tavano and Francesco Perri and Gabriele Capurso and Tamas Hussein and Mindaugas Kiudelis and Juozas Kupcinskas and Busch, {Olivier R.} and Luca Morelli and Theodoropoulos, {George E.} and Testoni, {Sabrina Gloria Giulia} and Kestutis Adamonis and Neoptolemos, {John P.} and Maria Gazouli and Claudio Pasquali and Zita Kormos and Pavel Skalicky and Raffaele Pezzilli and Cosimo Sperti and Emanuele Kauffmann and Buechler, {Markus W.} and Ben Schoettker and Peter Hegyi and Giovanni Capretti and Lawlor, {Rita T.} and Federico Canzian and Daniele Campa",

note = "Publisher Copyright: {\textcopyright} 2024 UICC.",

year = "2024",

month = oct,

day = "15",

doi = "10.1002/ijc.35046",

language = "English",

volume = "155",

pages = "1432--1442",

journal = "International Journal of Cancer",

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Corradi, C, Lencioni, G, Felici, A, Rizzato, C, Gentiluomo, M, Ermini, S, Archibugi, L, Mickevicius, A, Lucchesi, M, Malecka-Wojciesko, E, Basso, D, Arcidiacono, PG, Petrone, MC, Carrara, S, Goetz, M, Bunduc, S, Holleczek, B, Aoki, MN, Uzunoglu, FG, Zanette, DL, Mambrini, A, Jamroziak, K, Oliverius, M, Lovecek, M, Cavestro, GM, Milanetto, AC, Peduzzi, G, Duchonova, BM, Izbicki, JR, Zalinkevicius, R, Hlavac, V, van Eijck, CHJ, Brenner, H, Vanella, G, Vokacova, K, Soucek, P, Tavano, F, Perri, F, Capurso, G, Hussein, T, Kiudelis, M, Kupcinskas, J, Busch, OR, Morelli, L, Theodoropoulos, GE, Testoni, SGG, Adamonis, K, Neoptolemos, JP, Gazouli, M, Pasquali, C, Kormos, Z, Skalicky, P, Pezzilli, R, Sperti, C, Kauffmann, E, Buechler, MW, Schoettker, B, Hegyi, P, Capretti, G, Lawlor, RT, Canzian, F & Campa, D 2024, 'Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk', International Journal of Cancer, vol. 155, no. 8, pp. 1432-1442. https://doi.org/10.1002/ijc.35046

TY - JOUR

T1 - Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

AU - Corradi, Chiara

AU - Lencioni, Giulia

AU - Felici, Alessio

AU - Rizzato, Cosmeri

AU - Gentiluomo, Manuel

AU - Ermini, Stefano

AU - Archibugi, Livia

AU - Mickevicius, Antanas

AU - Lucchesi, Maurizio

AU - Malecka-Wojciesko, Ewa

AU - Basso, Daniela

AU - Arcidiacono, Paolo Giorgio

AU - Petrone, Maria Chiara

AU - Carrara, Silvia

AU - Goetz, Mara

AU - Bunduc, Stefania

AU - Holleczek, Bernd

AU - Aoki, Mateus Nobrega

AU - Uzunoglu, Faik G.

AU - Zanette, Dalila Luciola

AU - Mambrini, Andrea

AU - Jamroziak, Krzysztof

AU - Oliverius, Martin

AU - Lovecek, Martin

AU - Cavestro, Giulia Martina

AU - Milanetto, Anna Caterina

AU - Peduzzi, Giulia

AU - Duchonova, Beatrice Mohelnikova

AU - Izbicki, Jakob R.

AU - Zalinkevicius, Rimantas

AU - Hlavac, Viktor

AU - van Eijck, Casper H. J.

AU - Brenner, Hermann

AU - Vanella, Giuseppe

AU - Vokacova, Klara

AU - Soucek, Pavel

AU - Tavano, Francesca

AU - Perri, Francesco

AU - Capurso, Gabriele

AU - Hussein, Tamas

AU - Kiudelis, Mindaugas

AU - Kupcinskas, Juozas

AU - Busch, Olivier R.

AU - Morelli, Luca

AU - Theodoropoulos, George E.

AU - Testoni, Sabrina Gloria Giulia

AU - Adamonis, Kestutis

AU - Neoptolemos, John P.

AU - Gazouli, Maria

AU - Pasquali, Claudio

AU - Kormos, Zita

AU - Skalicky, Pavel

AU - Pezzilli, Raffaele

AU - Sperti, Cosimo

AU - Kauffmann, Emanuele

AU - Buechler, Markus W.

AU - Schoettker, Ben

AU - Hegyi, Peter

AU - Capretti, Giovanni

AU - Lawlor, Rita T.

AU - Canzian, Federico

AU - Campa, Daniele

PY - 2024/10/15

Y1 - 2024/10/15

N2 - 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.

AB - 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.

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U2 - 10.1002/ijc.35046

DO - 10.1002/ijc.35046

M3 - Article

C2 - 38924078

SN - 0020-7136

VL - 155

SP - 1432

EP - 1442

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 8

ER -