title: Genome-wide analysis of the role of copy-number variation in pancreatic cancer risk.
abstract: Although family history is a risk factor for pancreatic adenocarcinoma, much of the genetic etiology of this disease remains unknown. While genome-wide association studies have identified some common single nucleotide polymorphisms (SNPs) associated with pancreatic cancer risk, these SNPs do not explain all the heritability of this disease. We hypothesized that copy number variation (CNVs) in the genome may play a role in genetic predisposition to pancreatic adenocarcinoma. Here, we report a genome-wide analysis of CNVs in a small hospital-based, European ancestry cohort of pancreatic cancer cases and controls. Germline CNV discovery was performed using the Illumina Human CNV370 platform in 223 pancreatic cancer cases (both sporadic and familial) and 169 controls. Following stringent quality control, we asked if global CNV burden was a risk factor for pancreatic cancer. Finally, we performed in silico CNV genotyping and association testing to discover novel CNV risk loci. When we examined the global CNV burden, we found no strong evidence that CNV burden plays a role in pancreatic cancer risk either overall or specifically in individuals with a family history of the disease. Similarly, we saw no significant evidence that any particular CNV is associated with pancreatic cancer risk. Taken together, these data suggest that CNVs do not contribute substantially to the genetic etiology of pancreatic cancer, though the results are tempered by small sample size and large experimental variability inherent in array-based CNV studies.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA ; Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Willis
authors.affiliation: Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Semanti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.affiliation: Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA ; Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kurtz
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA ; Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Klein
keywords: CNVs; SNP microarrays; cancer risk; copy number variation; pancreatic cancer