Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

Chiara Corradi¹, Giulia Lencioni¹, Alessio Felici¹, Cosmeri Rizzato¹, Manuel Gentiluomo¹, Stefano Ermini², Livia Archibugi^{3

4}, Antanas Mickevicius⁵, Maurizio Lucchesi⁶, Ewa Malecka-Wojciesko⁷, Daniela Basso⁸, Paolo Giorgio Arcidiacono³, Maria Chiara Petrone³, Silvia Carrara⁹, Mara Götz¹⁰, Stefania Bunduc^{11

12

13

14}, Bernd Holleczek¹⁵, Mateus Nóbrega Aoki¹⁶, Faik G Uzunoglu¹⁰, Dalila Lucíola Zanette¹⁶, Andrea Mambrini⁶, Krzysztof Jamroziak¹⁷, Martin Oliverius¹⁸, Martin Lovecek¹⁹, Giulia Martina Cavestro²⁰, Anna Caterina Milanetto²¹, Giulia Peduzzi¹, Beatrice Mohelnikova Duchonova²², Jakob R Izbicki¹⁰, Rimantas Zalinkevicius²³, Viktor Hlavac²⁴, Casper H J van Eijck²⁵, Hermann Brenner^{26

27

28}, Giuseppe Vanella^{3

4}, Klara Vokacova^{29

30}, Pavel Soucek²⁴, Francesca Tavano³¹, Francesco Perri³¹, Gabriele Capurso^{3

4}, Tamás Hussein^{13

14}, Mindaugas Kiudelis⁵, Juozas Kupcinskas³², Olivier R Busch³³, Luca Morelli³⁴, George E Theodoropoulos³⁵, Sabrina Gloria Giulia Testoni³, Kestutis Adamonis^{32

33}, John P Neoptolemos³⁵, Maria Gazouli³⁶, Claudio Pasquali²¹, Zita Kormos¹⁴, Pavel Skalicky¹⁹, Raffaele Pezzilli³⁷, Cosimo Sperti²¹, Emanuele Kauffmann³⁸, Markus W Büchler³⁹, Ben Schöttker²⁶, Péter Hegyi^{13

14

40

41}, Giovanni Capretti^{42

43}, Rita T Lawlor⁴⁴, Federico Canzian⁴⁵, Daniele Campa¹

Affiliations

¹ Department of Biology, University of Pisa, Pisa, Italy.
² Blood Transfusion Service, Azienda Ospedaliera-Universitaria Meyer, Children's Hospital, Florence, Italy.
³ Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, IRSSC San Raffaele Scientific Institute, Milan, Italy.
⁴ Digestive and Liver Disease Unit, Sant'Andrea Hospital, Rome, Italy.
⁵ Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁶ Oncology of Massa Carrara, Oncological Department, Azienda USL Toscana Nord Ovest, Carrara, Italy.
⁷ Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
⁸ Laboratory Medicine, Department DIMED, University of Padova, Padua, Italy.
⁹ Endoscoopic Unit, Gastroenterology Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁰ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
¹² Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania.
¹³ Center for Translational Medicine, Semmelweis University, Budapest, Hungary.
¹⁴ Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
¹⁵ Saarland Cancer Registry, Saarbrücken, Germany.
¹⁶ Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, Parana, Brazil.
¹⁷ Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
¹⁸ Department of Surgery, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁹ University Hospital Olomouc, Olomouc, Czech Republic.
²⁰ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²¹ Department of DiSCOG, University of Padova, Padua, Italy.
²² Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
²³ Clinics of Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁴ Faculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, Czech Republic.
²⁵ Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
²⁶ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁷ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
²⁸ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁹ Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
³⁰ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
³¹ Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
³² Gastroenterology Department, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
³³ Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
³⁴ General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
³⁵ First Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁶ Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁷ Potenza County Medical Association, Potenza, Italy.
³⁸ Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy.
³⁹ Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
⁴⁰ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁴¹ János Szentágothai Research Center, University of Pécs, Pécs, Hungary.
⁴² Pancreatic Surgery Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
⁴³ Humanitas University, Rozzano, Milan, Italy.
⁴⁴ ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
⁴⁵ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

PMID: 38924078
DOI: 10.1002/ijc.35046

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

Chiara Corradi et al. Int J Cancer. 2024.

. 2024 Oct 15;155(8):1432-1442.

doi: 10.1002/ijc.35046. Epub 2024 Jun 26.

Authors

Affiliations

¹ Department of Biology, University of Pisa, Pisa, Italy.
² Blood Transfusion Service, Azienda Ospedaliera-Universitaria Meyer, Children's Hospital, Florence, Italy.
³ Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, IRSSC San Raffaele Scientific Institute, Milan, Italy.
⁴ Digestive and Liver Disease Unit, Sant'Andrea Hospital, Rome, Italy.
⁵ Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁶ Oncology of Massa Carrara, Oncological Department, Azienda USL Toscana Nord Ovest, Carrara, Italy.
⁷ Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
⁸ Laboratory Medicine, Department DIMED, University of Padova, Padua, Italy.
⁹ Endoscoopic Unit, Gastroenterology Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁰ Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹¹ Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
¹² Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest, Romania.
¹³ Center for Translational Medicine, Semmelweis University, Budapest, Hungary.
¹⁴ Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
¹⁵ Saarland Cancer Registry, Saarbrücken, Germany.
¹⁶ Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, Parana, Brazil.
¹⁷ Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
¹⁸ Department of Surgery, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁹ University Hospital Olomouc, Olomouc, Czech Republic.
²⁰ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²¹ Department of DiSCOG, University of Padova, Padua, Italy.
²² Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
²³ Clinics of Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²⁴ Faculty of Medicine in Pilsen, Biomedical Center, Charles University, Pilsen, Czech Republic.
²⁵ Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
²⁶ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁷ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
²⁸ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
²⁹ Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
³⁰ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
³¹ Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
³² Gastroenterology Department, Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
³³ Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
³⁴ General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
³⁵ First Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁶ Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
³⁷ Potenza County Medical Association, Potenza, Italy.
³⁸ Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy.
³⁹ Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
⁴⁰ Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
⁴¹ János Szentágothai Research Center, University of Pécs, Pécs, Hungary.
⁴² Pancreatic Surgery Department, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
⁴³ Humanitas University, Rozzano, Milan, Italy.
⁴⁴ ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
⁴⁵ Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

PMID: 38924078
DOI: 10.1002/ijc.35046

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.

Keywords: DNA methylation; pancreatic cancer; risk factors; single‐nucleotide polymorphism.

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References

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Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

Affiliations

Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk

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