CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype
2008

CYP2C19 Function in Advanced Cancer

Sample size: 33 publication Evidence: moderate

Author Information

Author(s): Helsby N A, Lo W-Y, Sharples K, Riley G, Murray M, Spells K, Dzhelai M, Simpson A, Findlay M

Primary Institution: University of Auckland

Hypothesis

Is CYP2C19 activity decreased in patients with advanced cancer?

Conclusion

CYP2C19 activity is significantly compromised in advanced cancer patients, leading to a higher incidence of poor metaboliser status than expected based on genotype.

Supporting Evidence

  • 37% of patients with normal CYP2C19 genotype were found to be poor metabolizers.
  • The study indicates that genotyping for CYP2C19 may underestimate the number of phenotypic poor metabolizers in cancer patients.
  • No correlation was found between compromised CYP2C19 activity and proinflammatory cytokines.

Takeaway

In cancer patients, a key enzyme that helps break down certain drugs doesn't work as well as it should, which can affect how well treatments work.

Methodology

CYP2C19 genotype was determined in 33 advanced cancer patients, and enzyme activity was evaluated using the probe drug omeprazole.

Potential Biases

Potential bias due to the self-reported ethnicity of patients and the exclusion of those on certain medications.

Limitations

The study had a small sample size and did not assess the relationship between CYP2C19 activity and all potential inflammatory markers.

Participant Demographics

33 advanced cancer patients (18 male, 15 female), primarily Caucasian with one Asian patient, aged 33 to 79 years.

Statistical Information

P-Value

p=0.03

Statistical Significance

p<0.0005

Digital Object Identifier (DOI)

10.1038/sj.bjc.6604699

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