The Study: Two prospective genomic databases from one German and one Swiss institution were queried for resected pancreatic cancers with both sufficient DNA and sufficient clinical data for analysis. In the end, there was germline DNA from 195 German/Swiss subjects, on which testing revealed two standout single nucleotide polymorphisms (SNPs) on the CHI3L2 and CD44 genes that appeared to be highly-associated with cancer-specific survival. In an attempt to minimize the chance that this happened by chance—they did start out with over 2 million possible SNPs, after all—the effects were validated independently among 136 subjects with resected pancreatic cancer in the Cancer Genome Atlas (TCGA). When both groups were combined, the 70 who had a high-risk allele in either gene had a 2.7-fold greater risk of cancer death than the 261 without one. What’s more, this significantly improved the power of predictive models over stage and margin status alone. Add that to what we already know about pancreatic cancer genomic predictors.
Bottom Line: Patients with resectable pancreatic cancer who harbor either of two identified high-risk alleles, as can be determined by a simple blood test, may merit additional therapy on trial as chances are low they will reach modern-day median survival times with standard therapy. | Dimitrakopoulos, JAMA Surg 2019