Authors

Beatrice Mohelnikova-Duchonova, National Institute of Public Health, Prague
Ondrej Strouhal, Palacky University Medical School and Teaching Hospital
David J Hughes, Royal College of Surgeons in IrelandFollow
Ivana Holcatova, Charles University in Prague
Martin Oliverius, Institute of Clinical and Experimental Medicine, Prague
Zdenek Kala, The University Hospital and Faculty of Medicine, Brno Bohunice
Daniele Campa, German Cancer Research Center (DKFZ)
Cosmeri Rizzato, German Cancer Research Center (DKFZ)
Federico Canzian, German Cancer Research Center (DKFZ)
Raffaele Pezzilli, Sant'Orsola-Malpighi Hospital
Renata Talar-Wojnarowska, Medical University of Lodz
Ewa Malecka-Panas, Medical University of Lodz
Cosimo Sperti, University of Padova
Carlo Federico Zambon, University of Padova
Sergio Pedrazzoli, University of Padova
Paola Fogar, University-Hospital of Padova
Anna Caterina Milanetto, University of Padova
Gabriele Capurso, 'Sapienza' University of Rome
Gianfranco Delle Fave, 'Sapienza' University of Rome
Roberto Valente, 'Sapienza' University of Rome
Maria Gazouli, University of Athens
Giuseppe Malleo, University and Hospital Trust of Verona
Rita Teresa Lawlor, University and Hospital Trust of Verona
Oliver Strobel, Heidelberg University Hospital
Thilo Hackert, Heidelberg University Hospital
Nathalia Giese, Heidelberg University Hospital
Pavel Vodicka, Academy of Science of Czech Republic
Ludmila Vodickova, Academy of Science of Czech Republic
Stefano Landi, University of Pisa
Francesca Tavano, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"
Domenica Gioffreda, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"
Ada Piepoli, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"
Valerio Pazienza, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza"
Andrea Mambrini, Azienda USL 1 Massa Carrara
Mariangela Pedata, Azienda USL 1 Massa Carrara
Maurizio Cantore, Azienda USL 1 Massa Carrara
Franco Bambi, Azienda Ospedaliero Universitaria
Stefano Ermini, Azienda Ospedaliero Universitaria
Niccola Funel, University of Pisa
Radmila Lemstrova, Palacky University Medical School and Teaching Hospital
Pavel Soucek, National Institute of Public Health, Prague

Peer Reviewed

1

Document Type

Article

Publication Date

8-3-2017

Keywords

Polymorphism, Single Nucleotide, pancreatic cancer

Comments

The original article is available at www.nature.com

Abstract

Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted.

Disciplines

Physics | Physiology

Citation

Mohelnikova-Duchonova B, Strouhal O, Hughes DJ, Holcatova I, Oliverius M, Kala Z et al. SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. Scientific reports. 2017;7:43812.

PubMed ID

28272475

DOI Link

10.1038/srep43812

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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