Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

Gentiluomo, Manuel; Galeotti, Alice; Pezzilli, Raffaele; Boggi, Ugo; Capurso, Gabriele; Małecka-Panas, Ewa; Kupčinskas, Juozas; Büchler, Markus Wolfgang; Andriulli, Angelo; Greenhalf, William; Neoptolemos, John P.; Mambrini, Andrea; Scarpa, Aldo; Soucek, Pavel; Lovecek, Martin; Mohelnikova-Duchonova, Beatrice; Puchalt García, Paula; Obazee, Ofure; Pasquali, Claudio; Busch, Olivier RC

doi:10.1016/j.pan.2018.05.096

Use this url to cite publication: https://hdl.handle.net/20.500.12512/97769

Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

Type of publication

Tezės Web of Science duomenų bazėje / Theses in Web of Science database (T1a1)

Author(s)

Author	Affiliation
Gentiluomo, Manuel

Title

Genetic variability of the ABCC2 gene and overall survival in pancreatic cancer

Manuel Gentiluomo, Alice Galeotti, Raffaele Pezzilli, Ugo Boggi, Gabriele Capurso, Ewa Małecka-Panas, Juozas Kupcinskas, Markus Büchler, Angelo Andriulli, William Greenhalf, John P. Neoptolemos, Andrea Mambrini, Aldo Scarpa, Pavel Soucek, Martin Lovecek, Beatrice Mohelnikova-Duchonova, Paula Puchalt García, Ofure Obazee, Claudio Pasquali, Olivier Busch, Jakob R. Izbicki, Yogesh K. Vashist, Giulia M. Cavestro, Peter Hegyi, Federico Canzian, Daniele Campa

Publisher (trusted)

Karger

Elsevier

Is Referenced by

MEDLINE (PubMed)

Science Citation Index Expanded

Date Issued

Date
2018-06-13

Extent

p. S36-S36, no. P2-069.

Is part of

Pancreatology : Abstract book of the 50th Jubilee Meeting of the European Pancreatic Club : 13-16 June 2018, Berlin, Germany / Organization: INTERPLAN Congress, Meeting & Event Management AG. Basel ; New York ; New Delhi : Karger ; Elsevier, 2018, vol. 18, iss. 4, suppl.

Version

Originalus / Original

Series/Report no.

4. Genetics in pancreatic diseases.

Field of Science

Keywords (en)

Abstract (en)

Objectives Context: The critical role of the ATP binding cassette subfamily C member 2 (ABCC2) protein in the response to various drugs has been documented in several reports. It is more recent knowledge that the ABCC2 gene is differently expressed in gemcitabine sensitive and resistant cells. Moreover, Single Nucleotide Polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types. Objective: The aim of this study was to investigate the possible association between SNPs in the ABCC2 gene and overall survival in PDAC patients. Methods A total of 12 polymorphisms, including tagging-SNPs covering all the genetic variability of the ABCC2 gene, enriched by eQTL SNPs, were selected and genotyped in 3167 PDAC patients collected in the context the PANcreatic Disease ReseArch (PANDoRA) consortium. The association between ABCC2 SNPs and PDAC overall survival (OS) have been tested using Cox proportional hazard models. Results Considering all the patients together we did not observe any statistically significant association, however stratifying by stage we observed that two SNPs, rs3740067 and rs3740073, showed an association with worse OS (HR=2.19, 95% CI 1.38-6.17, p = 0.0052, and HR=2.75, 95% CI 1.34-5.62, p = 0.0057 respectively) in stage I patients. These two SNPs are strong modulators of gene expression in the pancreatic tissue according to the GTEx portal. Conclusion Our results suggest