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, P. 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: Contribution to journalArticle

1 Citation (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 - Apr 1 2019

Fingerprint

Pancreatic Neoplasms
Adenocarcinoma
Adenosine Triphosphate
Single Nucleotide Polymorphism
Genes
Confidence Intervals
gemcitabine
Survival
Pancreatic Diseases
Proportional Hazards Models
Alleles
Research
Pharmaceutical Preparations
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research

Cite this

Gentiluomo, M., García, P. P., Galeotti, A. A., Talar-Wojnarowska, R., Tjaden, C., Tavano, F., ... 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

Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. / Gentiluomo, Manuel; García, Paula Puchalt; Galeotti, Alice Alessandra; Talar-Wojnarowska, Renata; Tjaden, Christine; Tavano, Francesca; Strobel, Oliver; Kupcinskas, Juozas; Neoptolemos, John; Hegyi, P.; Costello, Eithne; Pezzilli, Raffaele; Sperti, Cosimo; Lawlor, Rita T.; Capurso, Gabriele; Szentesi, Andrea; Soucek, Pavel; Vodicka, Pavel; Lovecek, Martin; Hackert, Thilo; Cavestro, Giulia Martina; Milanetto, Anna Caterina; Canzian, Federico; Campa, Daniele.

In: Carcinogenesis, Vol. 40, No. 4, 01.04.2019, p. 544-550.

Research output: Contribution to journalArticle

Gentiluomo, M, García, PP, Galeotti, AA, Talar-Wojnarowska, R, Tjaden, C, Tavano, F, Strobel, O, Kupcinskas, J, Neoptolemos, J, Hegyi, P, Costello, E, Pezzilli, R, Sperti, C, Lawlor, RT, Capurso, G, Szentesi, A, Soucek, P, Vodicka, P, Lovecek, M, Hackert, T, Cavestro, GM, Milanetto, AC, Canzian, F & Campa, D 2019, 'Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients', Carcinogenesis, vol. 40, no. 4, pp. 544-550. https://doi.org/10.1093/carcin/bgz006
Gentiluomo M, García PP, Galeotti AA, Talar-Wojnarowska R, Tjaden C, Tavano F et al. Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. Carcinogenesis. 2019 Apr 1;40(4):544-550. https://doi.org/10.1093/carcin/bgz006
Gentiluomo, Manuel ; García, Paula Puchalt ; Galeotti, Alice Alessandra ; Talar-Wojnarowska, Renata ; Tjaden, Christine ; Tavano, Francesca ; Strobel, Oliver ; Kupcinskas, Juozas ; Neoptolemos, John ; Hegyi, P. ; Costello, Eithne ; Pezzilli, Raffaele ; Sperti, Cosimo ; Lawlor, Rita T. ; Capurso, Gabriele ; Szentesi, Andrea ; Soucek, Pavel ; Vodicka, Pavel ; Lovecek, Martin ; Hackert, Thilo ; Cavestro, Giulia Martina ; Milanetto, Anna Caterina ; Canzian, Federico ; Campa, Daniele. / Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients. In: Carcinogenesis. 2019 ; Vol. 40, No. 4. pp. 544-550.
@article{6e125b6e12f0495099994ad15e758dd4,
title = "Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients",
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.",
author = "Manuel Gentiluomo and Garc{\'i}a, {Paula Puchalt} and Galeotti, {Alice Alessandra} and Renata Talar-Wojnarowska and Christine Tjaden and Francesca Tavano and Oliver Strobel and Juozas Kupcinskas and John Neoptolemos and P. Hegyi and Eithne Costello and Raffaele Pezzilli and Cosimo Sperti and Lawlor, {Rita T.} and Gabriele Capurso and Andrea Szentesi and Pavel Soucek and Pavel Vodicka and Martin Lovecek and Thilo Hackert and Cavestro, {Giulia Martina} and Milanetto, {Anna Caterina} and Federico Canzian and Daniele Campa",
year = "2019",
month = "4",
day = "1",
doi = "10.1093/carcin/bgz006",
language = "English",
volume = "40",
pages = "544--550",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients

AU - Gentiluomo, Manuel

AU - García, Paula Puchalt

AU - Galeotti, Alice Alessandra

AU - Talar-Wojnarowska, Renata

AU - Tjaden, Christine

AU - Tavano, Francesca

AU - Strobel, Oliver

AU - Kupcinskas, Juozas

AU - Neoptolemos, John

AU - Hegyi, P.

AU - Costello, Eithne

AU - Pezzilli, Raffaele

AU - Sperti, Cosimo

AU - Lawlor, Rita T.

AU - Capurso, Gabriele

AU - Szentesi, Andrea

AU - Soucek, Pavel

AU - Vodicka, Pavel

AU - Lovecek, Martin

AU - Hackert, Thilo

AU - Cavestro, Giulia Martina

AU - Milanetto, Anna Caterina

AU - Canzian, Federico

AU - Campa, Daniele

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85067636531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067636531&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgz006

DO - 10.1093/carcin/bgz006

M3 - Article

C2 - 30629142

AN - SCOPUS:85067636531

VL - 40

SP - 544

EP - 550

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 4

ER -