SynthesisInternational journal of cancer2022
Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis.
Synthesis in International journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Chymotrypsin Deficiency Accelerates Precancerous Remodeling of the Pancreas in KC Mice.Pancreas · 2026Article
- Unveiling the mechanistic links between plasticizers and gastric cancer via network toxicology and molecular docking approaches.BMC pharmacology & toxicology · 2025Article
- MisfoldingAmerican journal of physiology. Gastrointestinal and liver physiology · 2025Article
- METTL3 mediates CPB1 expression by regulating transcription factor BACH2 to promote apoptosis and oxidative stress of lens epithelial cells.Journal of bioenergetics and biomembranes · 2025Article
- Article
- Article
- Understanding familial risk of pancreatic ductal adenocarcinoma.Familial cancer · 2024Review
- Precursor lesions in familial and hereditary pancreatic cancer.Familial cancer · 2024Review
- Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention.Gastroenterology · 2023Article
- Review
- Novel p.G250A Mutation Associated with Chronic Pancreatitis Highlights Misfolding-Prone Region in Carboxypeptidase A1 (CPA1).International journal of molecular sciences · 2022Article
- Endoplasmic stress-inducing variants in carboxyl ester lipase and pancreatic cancer risk.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- Familial Pancreatic Cancer.Gastroenterology clinics of North America · 2022Review
- Screening for pancreatic cancer has the potential to save lives, but is it practical?Expert review of gastroenterology & hepatologyReview
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Gene variants that encode pancreatic enzymes with impaired secretion can induce pancreatic acinar endoplasmic reticulum (ER) stress, cellular injury and pancreatitis. The role of such variants in pancreatic cancer risk has received little attention. We compared the prevalence of ER stress-inducing variants in CPA1 and CPB1 in patients with pancreatic ductal adenocarcinoma (PDAC cases), enrolled in the National Familial Pancreas Tumor Registry, to their prevalence in noncancer controls in the Genome Aggregation Database (gnomAD). Variants of unknown significance were expressed and variants with reduced secretion assessed for ER stress induction. In vitro assessments were compared with software predictions of variant function. Protein variant software was used to assess variants found in only one gnomAD control ("n-of-one" variants). A meta-analysis of prior PDAC case/control studies was also performed. Of the 1385 patients with PDAC, 0.65% were found to harbor an ER stress-inducing variant in CPA1 or CPB1, compared to 0.17% of the 64 026 controls (odds ratio [OR]: 3.80 [1.92-7.51], P = .0001). ER stress-inducing variants in the CPA1 gene were identified in 4 of 1385 PDAC cases vs 77 of 64 026 gnomAD controls (OR: 2.4 [0.88-6.58], P = .087), and variants in CPB1 were detected in 5 of 1385 cases vs 33 of 64 026 controls (OR: 7.02 [2.74-18.01], P = .0001). Meta-analysis demonstrated strong associations for pancreatic cancer and ER-stress inducing variants for both CPA1 (OR: 3.65 [1.58-8.39], P < .023) and CPB1 (OR: 9.51 [3.46-26.15], P < .001). Rare variants in CPB1 and CPA1 that induce ER stress are associated with increased odds of developing pancreatic cancer.
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