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posted on 22.11.2019by 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 Valente, Maria 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
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.
This study was supported by the projects CSF no.: P301/12/1734, MH CZ no. 16-28375A, MH CZ - DRO (National Institute of Public Health – NIPH, 75010330), and National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic, Prvouk-P27/LF1/1, AIRC 5xmille (grant no. 12182), Italian Cancer Genome Project (FIRB RBAP10AHJB); FIMP, Ministero Salute CUP_ J33G13000210001, Pancobank (Prof. M.W. Büchler) and team supported by Heidelberger Stiftung Chirurgie, BMBF grants 01GS08114 and 01ZX1305C, EU ERA-Net TRANSCAN 01KT1506 as well as BMBH (Prof. P. Schirmacher; BMBF grant 01EY1101), the Italian Ministry of Health grants (RC1503GA42, RC1503GA43) to the Division of Gastroenterology, IRCCS “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, Italy.
The original article is available at www.nature.com
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.