TY - JOUR
T1 - Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients
AU - Rizzato, Cosmeri
AU - Campa, Daniele
AU - Talar-Wojnarowska, Renata
AU - Halloran, Christopher
AU - Kupcinskas, Juozas
AU - Butturini, Giovanni
AU - Mohelníková-Duchoňová, Beatrice
AU - Sperti, Cosimo
AU - Tjaden, Christine
AU - Ghaneh, Paula
AU - Hackert, Thilo
AU - Funel, Niccola
AU - Giese, Nathalia
AU - Tavano, Francesca
AU - Pezzilli, Raffaele
AU - Pedata, Mariangela
AU - Pasquali, Claudio
AU - Gazouli, Maria
AU - Mambrini, Andrea
AU - Souček, Pavel
AU - di Sebastiano, Pierluigi
AU - Capurso, Gabriele
AU - Cantore, Maurizio
AU - Oliverius, Martin
AU - Offringa, Rienk
AU - Małecka-Panas, Ewa
AU - Strobel, Oliver
AU - Scarpa, Aldo
AU - Canzian, Federico
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10-5) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials.
AB - Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10-5) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials.
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U2 - 10.1093/carcin/bgw080
DO - 10.1093/carcin/bgw080
M3 - Article
AN - SCOPUS:84991261659
VL - 37
SP - 957
EP - 964
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - 10
M1 - bgw080
ER -