Null Results in Brief Polymorphic Variants in Hereditary Pancreatic Cancer Genes Are Not Associated with Pancreatic Cancer Risk

Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, includ-ing BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hy-pothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development. Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-eight genes directly and indirectly involved in the Fanconi/BRCA pathway (includes BRCA1, BRCA2, and PALB2) were identified and 248 tag SNPs were se-lected. In addition, 11 SNPs in CDKN2A, PRSS1, and PRSS2 were selected. Association studies were done at the gene level by principal components analysis, where-as recursive partitioning analysis was used to investi-gate pathway effects. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. Results:Gene level analyses showed no significant asso-ciation of any genes with altered pancreatic cancer risk. Multiple single SNP analyses showed associations, which will require replication. Exploratory pathway analyses by recursive partitioning showed no associa-tion between SNPs and risk for pancreatic cancer. Conclusion: In a candidate gene and pathway SNP asso-ciation study analysis, common variations in the Fanco-ni/BRCA pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(9):OF1–4