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

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

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 criti...

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Gentiluomo Manuel
García Paula Puchalt
Galeotti Alice Alessandra
Talar-Wojnarowska Renata
Tjaden Christine
Tavano Francesca
Strobel Oliver
Kupcinskas Juozas
Neoptolemos John
Hegyi Péter
Costello Eithne
Pezzilli Raffaele
Sperti Cosimo
Lawlor Rita T.
Szentesi Andrea Ildikó
Dokumentumtípus: Cikk
Megjelent: 2019
Sorozat:CARCINOGENESIS 40 No. 4
doi:10.1093/carcin/bgz006

mtmt:30388152
Online Access:http://publicatio.bibl.u-szeged.hu/17953
Leíró adatok
Tartalmi kivonat: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 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 overall survival (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: HR=3.29, 95% 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.
Terjedelem/Fizikai jellemzők:544-550
ISSN:0143-3334

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