A Replication Study and Genome-wide Scan of Single Nucleotide Polymorphisms Associated with Pancreatic Cancer Risk and Overall Survival
Menée sur plusieurs cohortes de cas de cancer du pancréas et de témoins sains, cette étude américaine d'association sur le génome entier évalue l'association entre des polymorphismes à simple nucléotide, le risque de cancer du pancréas et la survie globale des patients
Purpose: To explore the effects of single nucleotide polymorphisms (SNPs) on pancreatic cancer risk and overall survival. Experimental Design: The germline DNA of 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. We analyzed putative risk SNPs for replication of their reported effects on risk and tested for novel effects on overall survival (OS). Similarly, we analyzed putative survival-associated SNPs for replication of their reported effects on OS and tested for novel effects on risk. Lastly, we performed a genome-wide association study of OS using a subset of 252 cases, with two subsequent validation sets of 261 and 572 patients, respectively. Results: Among seven risk SNPs analyzed, two (rs505922, rs9543325) were associated with risk (p less than 0.05). Among 24 survival-associated SNPs analyzed, one (rs9350) was associated with OS (p less than 0.05). No putative risk SNPs or putative survival-associated SNPs were found to be associated with OS or risk, respectively. Further, our GWAS identified a novel SNP (rs1482426, combined stage 1 and 2 p = 1.7 x10-6, per-allele HR = 1.74, 95% CI 1.38-2.18) to be putatively associated with OS. Conclusions: The effects of SNPs on pancreatic cancer risk and overall survival were replicated in our study, though 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.