CPB1 and Pancreatic Ductal Adenocarcinoma

CPB1 (HGNC:2299) has emerged as a candidate risk gene for pancreatic ductal adenocarcinoma (MONDO_0005184). Recent studies have investigated rare, ER stress‑inducing variants in CPB1 that may predispose individuals to pancreatic cancer, emphasizing a potential mechanistic link between aberrant protein function and carcinogenesis (PMID:34817877).

In a large case‑control study, 1385 PDAC patients were screened for deleterious variants, with 5 probands harboring CPB1 alterations, yielding an odds ratio of 7.02 and a meta‑analysis OR of 9.51, thereby reinforcing the gene–disease association (PMID:34817877). These data offer robust genetic evidence that CPB1 variants are significantly enriched in PDAC cases compared to population controls.

Nevertheless, a separate genetic association study in a Han Chinese cohort did not detect CPB1 variants, a finding that introduces a measure of variability in the observed associations (PMID:35171259). This discrepancy highlights the complexity of pancreatic cancer genetics and suggests potential population-specific effects or variable penetrance.

Functional assessments provide additional support; in vitro mutagenesis and kinetic analyses of CPB1 protein products have demonstrated that specific amino acid changes can markedly impair enzyme activity. One reported variant, c.1090G>T (p.Asp364Tyr), exemplifies how altered protein function may contribute to endoplasmic reticulum stress and subsequent cellular dysregulation (PMID:15262224).

The integration of genetic and experimental evidence suggests that CPB1 variants—although not uniformly detected across all cohorts—are mechanistically linked to pancreatic ductal adenocarcinoma through disruption of normal cellular homeostasis. The convergence of strong odds ratios in meta‑analyses with confirmatory functional data underscores the clinical relevance of CPB1 testing.

Key Take‑home sentence: Incorporating CPB1 variant screening into genetic testing panels can enhance risk assessment and diagnostic decision‑making in patients susceptible to pancreatic ductal adenocarcinoma.

References

• International Journal of Cancer • 2022 • Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case‑control study and meta‑analysis PMID:34817877
• N/A • 2021 • Genetic association study of pancreatic cancer in a Han Chinese cohort PMID:35171259
• Biochimica et Biophysica Acta • 2004 • Identification, characterization, and site‑directed mutagenesis of recombinant pentachlorophenol 4‑monooxygenase PMID:15262224

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