Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer

• DOI: 10.1073/pnas.1720588115
• Publication Date: 2018-04-19T15:15:22Z
• Authors: Koji Tamura; Jun Yu; Tatsuo Hata; Masaya Suenaga; Koji Shindo; Toshiya Abe; Anne MacGregor-Das; Michael Borges; Christopher L. Wo...; Matthew J. Weiss; Jin He; Marcia Irene Canto; Gloria M. Petersen; Steven Gallinger; Sapna Syngal; Randall E. Brand; Anil Rustgi; Sara H. Olson; Elena Stoffel; Michele L. Cote; George Zogopoulos; James B. Potash; Fernando S. Goes; Richard W. McCombie; Peter P. Zandi; Mehdi Pirooznia; Melissa Kramer; Jennifer Parla; James R. Eshleman; Nicholas J. Roberts; Ralph H. Hruban; Alison Patricia K...; Michael Goggins
• Keywords: Pancreatic enzymes

To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to cancer susceptibility, we sequenced the coding regions of CPB1 and other known pancreatitis susceptibility (PRSS1, CPA1, CTRC, SPINK1) a hospital series cases controls. Variants CPB1, CPA1 (encoding carboxypeptidase B1 A1), CTRC were evaluated second set with familial More deleterious variants, defined as having impaired protein secretion induction endoplasmic reticulum (ER) stress transfected HEK 293T cells, found (5/986, 0.5%) than controls (0/1,045, P = 0.027). Among cases, ER stress-inducing 4 593 (0.67%) vs. 0 967 additional (P 0.020), combined prevalence 9/1,579 0/2,012 < 0.01). also [7/1,546 1/2,012; 0.025; odds ratio, 9.36 (95% CI, 1.15-76.02)]. Overall, 16 (1%) 1,579 had an or variant, compared 1 2,068 0.00001). No candidate statistically significant differences variant between Our study indicates are associated implicate acinar cells development.