Endoplasmic Stress-inducing Variants in Carboxyl Ester Lipase and Pancreatic Cancer Risk

Overview

Journal Pancreatology

Specialties Endocrinology
Gastroenterology

Date 2022 Aug 22

PMID 35995657

Authors

Makoto Kawamoto

Takeichi Yoshida

Koji Tamura

Mohamad Dbouk

Marcia Irene Canto

Richard Burkhart

Jin He

Nicholas J Roberts

Alison P Klein

Michael Goggins

Affiliations

Soon will be listed here.

Abstract

Background: Endoplasmic reticulum (ER) stress-inducing variants in several pancreatic secretory enzymes have been associated with pancreatic disease. Multiple variants in CEL, encoding carboxyl ester lipase, are known to cause maturity-onset diabetes of the young (MODY8) but have not been implicated in pancreatic cancer risk.

Methods: The prevalence of ER stress-inducing variants in the CEL gene was compared among pancreatic cancer cases vs. controls. Variants were identified by next-generation sequencing and confirmed by Sanger sequencing. Variants of uncertain significance (VUS) were assessed for their effect on the secretion of CEL protein and variants with reduced protein secretion were evaluated to determine if they induced endoplasmic reticulum stress.

Results: ER stress-inducing CEL variants were found in 34 of 986 cases with sporadic pancreatic ductal adenocarcinoma, and 21 of 1045 controls (P = 0.055). Most of the variants were either the CEL-HYB1 variant, the I488T variant, or the combined CEL-HYB1/I488T variant; one case had a MODY8 variant.

Conclusion: This case/control analysis finds ER stress-inducing CEL variants are not associated with an increased likelihood of having pancreatic cancer.

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