Format

Send to

Choose Destination
Carcinogenesis. 2018 Mar 8;39(3):360-367. doi: 10.1093/carcin/bgx150.

Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms.

Author information

1
Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy.
2
Division of Gastroenterology and Research Laboratory, San Giovanni Rotondo, Italy.
3
Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
4
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
5
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
6
Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Padova, Italy.
7
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Im Neuenheimer Feld, Heidelberg, Germany.
8
Department of Laboratory Medicine, University Hospital of Padova, Padova, Italy.
9
Department of Surgical Oncology and Hepatobiliary Surgery, Metropolitan General Hospital, Pireas, Greece.
10
ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
11
Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.
12
Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
13
Department of Medicine - DIMED, University of Padova, Padova, Italy.
14
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
15
Department of Hematology, Medical University of Lodz, Lodz, Poland.
16
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
17
Department of Biology, University of Pisa, Pisa, Italy.
18
Genomic Epidemiology Group, German Cancer Research Centre (DKFZ), Heidelberg, Germany

Abstract

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes.

PMID:
29309705
DOI:
10.1093/carcin/bgx150
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center