SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival

Beatrice Mohelnikova-Duchonova, Ondrej Strouhal, David J. Hughes, Ivana Holcatova, Martin Oliverius, Zdenek Kala, Daniele Campa, Cosmeri Rizzato, Federico Canzian, Raffaele Pezzilli, Renata Talar-Wojnarowska, Ewa Malecka-Panas, Cosimo Sperti, Carlo Federico Zambon, Sergio Pedrazzoli, Paola Fogar, Anna Caterina Milanetto, Gabriele Capurso, Gianfranco Delle Fave, Roberto ValenteMaria Gazouli, Giuseppe Malleo, Rita Teresa Lawlor, Oliver Strobel, Thilo Hackert, Nathalia Giese, Pavel Vodicka, Ludmila Vodickova, Stefano Landi, Francesca Tavano, Domenica Gioffreda, Ada Piepoli, Valerio Pazienza, Andrea Mambrini, Mariangela Pedata, Maurizio Cantore, Franco Bambi, Stefano Ermini, Niccola Funel, Radmila Lemstrova, Pavel Soucek

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number43812
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - Mar 8 2017

ASJC Scopus subject areas

  • General

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    Mohelnikova-Duchonova, B., Strouhal, O., Hughes, D. J., Holcatova, I., Oliverius, M., Kala, Z., Campa, D., Rizzato, C., Canzian, F., Pezzilli, R., Talar-Wojnarowska, R., Malecka-Panas, E., Sperti, C., Federico Zambon, C., Pedrazzoli, S., Fogar, P., Milanetto, A. C., Capurso, G., Delle Fave, G., ... Soucek, P. (2017). SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. Scientific Reports, 7, [43812]. https://doi.org/10.1038/srep43812