TY - JOUR
T1 - A replication study and genome-wide scan of single-nucleotide polymorphisms associated with pancreatic cancer risk and overall survival
AU - Willis, Jason A.
AU - Olson, Sara H.
AU - Orlow, Irene
AU - Mukherjee, Semanti
AU - McWilliams, Robert R.
AU - Kurtz, Robert C.
AU - Klein, Robert J.
PY - 2012/7/15
Y1 - 2012/7/15
N2 - Purpose: To explore the effects of single-nucleotide polymorphisms (SNP) on pancreatic cancer risk and overall survival (OS). Experimental Design: The germ lineDNAof 531 pancreatic cancer cases and 305 healthy controls from a hospital-based study was genotyped at SNPs previously reported to be associated with pancreatic cancer risk or clinical outcome.Weanalyzed putative risk SNPs for replication of their reported effects on risk and tested for novel effects on OS. Similarly, we analyzed putative survival-associated SNPs for replication of their reported effects on OS and tested for novel effects on risk. Finally, we conducted a genome-wide association study (GWAS) ofOSusing a subset of 252 cases, with two subsequent validation sets of 261 and 572 patients, respectively. Results: Among seven risk SNPs analyzed, two (rs505922 and rs9543325) were associated with risk (P<0.05). Among 24 survival-associated SNPs analyzed, one (rs9350) was associated with OS (P<0.05). No putative risk SNPs or putative survival-associated SNPs were found to be associated with OS or risk, respectively. Furthermore, our GWAS identified a novel SNP [rs1482426, combined stage I and II, P = 1.7 × 10-6, per-allele HR, 1.74; 95% confidence interval (CI), 1.38-2.18] to be putatively associated with OS. Conclusions: The effects of SNPs on pancreatic cancer risk and OS were replicated in our study, although further work is necessary to understand the functional mechanisms underlying these effects. More importantly, the putative association with OS identified by GWAS suggests that GWAS may be useful in identifying SNPs associated with clinical outcome in pancreatic cancer.
AB - Purpose: To explore the effects of single-nucleotide polymorphisms (SNP) on pancreatic cancer risk and overall survival (OS). Experimental Design: The germ lineDNAof 531 pancreatic cancer cases and 305 healthy controls from a hospital-based study was genotyped at SNPs previously reported to be associated with pancreatic cancer risk or clinical outcome.Weanalyzed putative risk SNPs for replication of their reported effects on risk and tested for novel effects on OS. Similarly, we analyzed putative survival-associated SNPs for replication of their reported effects on OS and tested for novel effects on risk. Finally, we conducted a genome-wide association study (GWAS) ofOSusing a subset of 252 cases, with two subsequent validation sets of 261 and 572 patients, respectively. Results: Among seven risk SNPs analyzed, two (rs505922 and rs9543325) were associated with risk (P<0.05). Among 24 survival-associated SNPs analyzed, one (rs9350) was associated with OS (P<0.05). No putative risk SNPs or putative survival-associated SNPs were found to be associated with OS or risk, respectively. Furthermore, our GWAS identified a novel SNP [rs1482426, combined stage I and II, P = 1.7 × 10-6, per-allele HR, 1.74; 95% confidence interval (CI), 1.38-2.18] to be putatively associated with OS. Conclusions: The effects of SNPs on pancreatic cancer risk and OS were replicated in our study, although further work is necessary to understand the functional mechanisms underlying these effects. More importantly, the putative association with OS identified by GWAS suggests that GWAS may be useful in identifying SNPs associated with clinical outcome in pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=84863957459&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-11-2856
DO - 10.1158/1078-0432.CCR-11-2856
M3 - Article
C2 - 22665904
AN - SCOPUS:84863957459
SN - 1078-0432
VL - 18
SP - 3942
EP - 3951
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -