Mohelnikova-Duchonova, BeatriceBeatriceMohelnikova-DuchonovaStrouhal, OndrejOndrejStrouhalHughes, David J.David J.Hugheset al.2019-05-022019-05-022017 the A2017-03-08Scientific Reports2045-2322http://hdl.handle.net/10197/10280Expression 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.ElectronicenThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Pancreatic ductal carcinomaPancreatic neoplasmsOrganic cation transport proteinsSingle nucleotide polymorphismGenetic enhancer elementsKaplan-Meier estimateJournal Article7Article 4381210.1038/srep438122019-01-22P301/12/1734LO150375010330Prvouk-P27/LF1/112182FIRB RBAP10AHJBCUP_J33G1300021000101GS0811401ZX1305 CEU ERA-Net TRANSCAN 01KT150601EY1101RC1503GA42RC1503GA4216-28375Ahttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/