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.

ARC NET Applied research on Cancer Centre University and Hospital Trust of Verona Verona Italy

Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic

Blood Transfusion Service Children's Hospital Meyer Azienda Ospedaliero Universitaria Florence Italy

Clinica Chirurgica 4 University of Padova Italy

Department of Basic Medical Sciences Laboratory of Biology School of Medicine University of Athens Athens Greece

Department of Biology University of Pisa Pisa Italy

Department of Digestive Diseases Sant'Orsola Malpighi Hospital Bologna Italy

Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland

Department of General Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany

Department of Laboratory Medicine University Hospital of Padova Italy

Department of Medicine DIMED University of Padova Italy

Department of Molecular Biology of Cancer Institute of Experimental Medicine Academy of Science of Czech Republic Prague Czech Republic and 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Oncology Azienda USL 1 Massa Carrara Massa Carrara Italy

Department of Oncology Palacky University Medical School and Teaching Hospital Olomouc Czech Republic

Department of Physiology and Centre for Systems Medicine Royal College of Surgeons in Ireland Dublin 2 Ireland

Department of Surgery and Oncology University and Hospital Trust of Verona Verona Italy

Department of Surgery Oncology and Gastroenterology DiSCOG University of Padova Italy

Department of Surgery The University Hospital and Faculty of Medicine Brno Bohunice Czech Republic

Department of Toxicogenomics National Institute of Public Health Prague Czech Republic

Department of Translational Research and New Technologies in Medicine and Surgery University of Pisa Pisa Italy

Department of Transplantation Surgery Institute of Clinical and Experimental Medicine Prague Czech Republic

Digestive and Liver Disease Unit S Andrea Hospital 'Sapienza' University of Rome Rome Italy

Division of Gastroenterology and Research Laboratory IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza San Giovanni Rotondo Italy

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University Prague Prague Czech Republic

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