Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients

Manuel Gentiluomo, Paula Puchalt García, Alice Alessandra Galeotti, Renata Talar-Wojnarowska, Christine Tjaden, Francesca Tavano, Oliver Strobel, Juozas Kupcinskas, John Neoptolemos, Péter Hegyi, Eithne Costello, Raffaele Pezzilli, Cosimo Sperti, Rita T. Lawlor, Gabriele Capurso, Andrea Szentesi, Pavel Soucek, Pavel Vodicka, Martin Lovecek, Thilo HackertGiulia Martina Cavestro, Anna Caterina Milanetto, Federico Canzian, Daniele Campa

Research output: Article

2 Citations (Scopus)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially 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. The aim of this study was to investigate the possible association between SNPs in the ABCC2 gene and overall survival (OS) in PDAC patients. We analysed 12 polymorphisms, including tagging-SNPs covering all the genetic variability of the ABCC2 gene and genotyped them in 1415 PDAC patients collected within the Pancreatic Disease ReseArch (PANDoRA) consortium. We tested the association between ABCC2 SNPs and PDAC OS using Cox proportional hazard models. We analysed PDAC patients dividing them by stage and observed that the minor alleles of three SNPs showed an association with worse OS [rs3740067: hazard ratio (HR) = 3.29, 95% confidence interval (CI) = 1.56–6.97, P = 0.002; rs3740073: HR = 3.11, 95% CI = 1.52–6.38, P = 0.002 and rs717620: HR = 2.90, 95% CI = 1.41–5.95, P = 0.004, respectively] in stage I patients. In patients with more advanced PDAC, we did not observe any statistically significant association. Our results suggest that rs3740067, rs3740073 and rs717620 could be promising prognostic markers in stage I PDAC patients.

Original languageEnglish
Pages (from-to)544-550
Number of pages7
JournalCarcinogenesis
Volume40
Issue number4
DOIs
Publication statusPublished - ápr. 2019

ASJC Scopus subject areas

  • Cancer Research

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    Gentiluomo, M., García, P. P., Galeotti, A. A., Talar-Wojnarowska, R., Tjaden, C., Tavano, F., Strobel, O., Kupcinskas, J., Neoptolemos, J., Hegyi, P., Costello, E., Pezzilli, R., Sperti, C., Lawlor, R. T., Capurso, G., Szentesi, A., Soucek, P., Vodicka, P., Lovecek, M., ... Campa, D. (2019). Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. Carcinogenesis, 40(4), 544-550. https://doi.org/10.1093/carcin/bgz006