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Pancreatic cancer has one of the worst mortality rates of all cancers. Little is known about its etiology, particularly regarding inherited risk. The PanScan project, a genome-wide association study, identified several common polymorphisms affecting pancreatic cancer susceptibility. Single nucleotide polymorphisms (SNPs) in ABO, sonic hedgehog (SHH), telomerase reverse transcriptase (TERT), nuclear receptor subfamily 5, group A, member 2 (NR5A2) were found to be associated with pancreatic cancer risk. Moreover the scan identified loci on chromosomes 13q22.1 and 15q14, to which no known genes or other functional elements are mapped. We sought to replicate these observations in two additional, independent populations (from Germany and the UK), and also evaluate the possible impact of these SNPs on patient survival. We genotyped 15 SNPs in 690 cases of pancreatic ductal adenocarcinoma (PDAC) and in 1277 healthy controls. We replicated several associations between SNPs and PDAC risk. Furthermore we found that SNP rs8028529 was weakly associated with a better overall survival (OS) in both populations. We have also found that NR5A2 rs12029406_T allele was associated with a shorter survival in the German population. In conclusion, we found that rs8028529 could be, if these results are replicated, a promising marker for both risk and prognosis for this lethal disease.

Original publication

DOI

10.1371/journal.pone.0027921

Type

Journal article

Journal

PLoS One

Publication Date

2011

Volume

6

Keywords

ABO Blood-Group System, Adenocarcinoma, Adult, Aged, Carcinoma, Pancreatic Ductal, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Germany, Hedgehog Proteins, Humans, Linkage Disequilibrium, Male, Middle Aged, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, Receptors, Cytoplasmic and Nuclear, Risk Factors, Survival Analysis, Telomerase, United Kingdom, White People