PURPOSE: The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) delF508 variant, which is responsible for 86% of cystic fibrosis (CF) cases, is present in Caucasian populations at a frequency of 3-5%. The vast majority of CFTR delF508 carriers do not have CF. There is little information on health and disease in heterozygous delF508 individuals. Previous studies have suggested risk-enhancing and risk-reducing effects for various diseases, with sometimes conflicting conclusions. Our aims are to determine if heterozygous delF508, in the absence of CF, is associated with risks for certain cancers. We took a genotype-first approach in a retrospective exploratory case-control study to determine cancer risks of delF508 carriers. We tested this using a unique database of 50,778 whole exome sequences (WES) linked to the extensive electronic health record (EHR) data of patients of Geisinger Health System who consented to participate in the MyCode Community Health Initiative biobanking project.