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CYP2C9 polymorphism is not associated with elevated carcinoembryonic antigen levels

Background: Carcinoembryonic antigen (CEA) is a glycoprotein that can be elevated in a number of benign and malignant conditions. In colorectal cancer, it is used as a prognostic marker and to detect recurrence. However, it lacks specificity and may become elevated in individuals without a history of cancer or other identifiable cause leading to costly and invasive investigation. Objective: The aim of this study was to assess whether genetic polymorphisms in the liver enzyme CYP2C9 could explain high CEA levels in otherwise normal individuals. Design: This is a case-control study. Setting: Individuals were genotyped for the poor metabolizer (PM) alleles CYP2C9*2 and CYP2C9*3 using predesigned TaqMan single nucleotide polymorphisms assays. Patients and Methods: Nineteen individuals with previously clinically unexplained elevated CEA and 567 healthy Caucasian controls were included. Main Outcome Measures: Chi-square analysis was used to test for association of CYP2C9 genotype with plasma CEA concentration. Sample Size: Nineteen individuals with previously clinically unexplained elevated CEA and 567 healthy Caucasian controls were included. Results: Fifteen of the 19 individuals with previously high CEA had elevated plasma CEA (>3.0μg/L) on re-testing. The frequency of CYP2C9 PM alleles in these 15 patients was not significantly higher than the frequency in controls. Conclusion: CEA concentrations do not appear to be influenced by CYP2C9 genotype, so this cannot be used to explain elevated CEA in the absence of an obvious clinical cause. Limitation: Small sample size.