Journal Article

Pancreatic Cancer Susceptibility Loci and Their Role in Survival

Key, Tim J., Rizzato, Cosmeri, Werner, Jens, Rachakonda, P. Sivaramakrishna, Canzian, Federico, Kumar, Rajiv, Lorenzo-Bermejo, Justo, Schanné, Michaela, Burwinkel, Barbara, Neoptolemos, John P., Siddiq, Afshan, Giese, Nathalia, Khaw, Kay-tee, Costello, Eithne, Greenhalf, William, Büchler, Markus W., Bauer, Andrea, Campa, Daniele, Hoheisel, Jörg D.

2011

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: ABO Blood-Group System - genetics / ABO system / Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma - therapy / Adult / Aged / Biology / Biomarkers / Biomedical research / Body mass index / Breast cancer / Cancer / Cancer research / Carcinoma, Pancreatic Ductal - ethnology / Carcinoma, Pancreatic Ductal - genetics / Chromosome 13 / Chromosomes / Colorectal cancer / Development and progression / Disease susceptibility / Ethics / Etiology / Family medical history / Female / Gene Frequency / Genes / Genetic aspects / Genetic Predisposition to Disease - ethnology / Genetic Predisposition to Disease - genetics / Genome-wide association studies / Genome-Wide Association Study - methods / Genomes / Genomics / Genotype / Germany / Health aspects / Health care / Health risks / Hedgehog protein / Hedgehog Proteins - genetics / Humans / Linkage Disequilibrium / Loci / Male / Medical research / Medicine / Middle Aged / Mortality / Pancreatic cancer / Pancreatic Neoplasms - ethnology / Pancreatic Neoplasms - genetics / Polymorphism, Single Nucleotide / Population genetics / Populations / Receptors, Cytoplasmic and Nuclear - genetics / Risk / Risk Factors / RNA-directed DNA polymerase / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Studies / Surgery / Survival / Survival Analysis / Telomerase / Telomerase - genetics / Telomerase reverse transcriptase / United Kingdom / White People - genetics