内质网应激诱导羧基酯脂肪酶变体与胰腺癌风险。
Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk.
机构信息
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
出版信息
Pancreatology. 2022 Nov;22(7):959-964. doi: 10.1016/j.pan.2022.08.004. Epub 2022 Aug 17.
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.
背景
几种胰腺分泌酶中的内质网（ER）应激诱导变异与胰腺疾病有关。已知编码羧基酯脂肪酶的 CEL 中的多个变异可导致青年发病的成年型糖尿病（MODY8），但与胰腺癌风险无关。
方法
比较了胰腺癌病例与对照组中 CEL 基因中 ER 应激诱导变异的发生率。通过下一代测序鉴定变异，并通过 Sanger 测序确认。对意义不确定的变异（VUS）进行评估，以确定它们对 CEL 蛋白分泌的影响，并评估具有降低蛋白分泌的变异是否诱导内质网应激。
结果
在 986 例散发性胰腺导管腺癌病例和 1045 例对照中发现了 34 例 ER 应激诱导的 CEL 变异，而在 1045 例对照中发现了 21 例（P = 0.055）。大多数变异要么是 CEL-HYB1 变异，要么是 I488T 变异，要么是 CEL-HYB1/I488T 联合变异；一例为 MODY8 变异。
结论
这项病例对照分析发现，内质网应激诱导的 CEL 变异与增加患胰腺癌的可能性无关。
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