Hu C, et al. - In this case-control study, whether or not inherited germline mutations in cancer predisposition genes are related to increased risks of pancreatic cancer was investigated. Outcomes found mutations in 6 genes correlated with pancreatic cancer in 5.5% of all pancreatic cancer patients. These patients included 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer.

Methods

• Researchers performed a case-control analysis to identify pancreatic cancer predisposition genes.
• Patients with pancreatic cancer underwent longitudinal analysis for prognosis.
• Between October 12, 2000, and March 31, 2016, 3,030 pancreatic cancer patients were enrolled in a Mayo Clinic registry; last follow-up was performed on June 22, 2017.
• Reference controls were 123,136 individuals with exome sequence data in the public Genome Aggregation Database and 53,105 individuals in the Exome Aggregation Consortium database.
• They classified individuals based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.
• In coding regions of 21 cancer predisposition genes, they identified germline mutations by sequencing of products from a custom multiplex polymerase chain reaction-based panel.
• Via comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls, they assessed associations of genes with pancreatic cancer.

Results

• Comparison of 3,030 pancreatic cancer case patients (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls showed significant associations between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).