Strong Association of a Common Dihydropyrimidine Dehydrogenase Gene Polymorphism with Fluoropyrimidine-Related Toxicity in Cancer Patients
2008

DPYD Gene Polymorphism and Chemotherapy Toxicity

Sample size: 128 publication 10 minutes Evidence: high

Author Information

Author(s): Eva Gross, Birgit Busse, Matthias Riemenschneider, Steffi Neubauer, Katharina Seck, Hanns-Georg Klein, Marion Kiechle, Florian Lordick, Alfons Meindl

Primary Institution: Technische Universität München

Hypothesis

The study investigates the association between variations in the DPYD gene and the risk of severe toxicity in cancer patients undergoing fluoropyrimidine-based chemotherapy.

Conclusion

A common polymorphism in the DPYD gene significantly contributes to the risk of severe drug adverse effects in certain cancer patients treated with fluoropyrimidine drugs.

Supporting Evidence

  • The study identified a significant association between the c.496A>G polymorphism and severe toxicity in cancer patients.
  • Carriers of the c.496G allele had a higher incidence of grade III and IV toxicity.
  • The attributable risk for severe drug-adverse effects due to the c.496G allele was found to be 56.9%.
  • The findings suggest that genetic testing for DPYD variants could help tailor chemotherapy doses.

Takeaway

Some people have a gene that makes them more likely to get sick from certain cancer medicines, and knowing this can help doctors give safer doses.

Methodology

The study analyzed the entire coding region of the DPYD gene in cancer patients with varying tolerance to fluoropyrimidine chemotherapy, using logistic regression and sliding window approaches.

Potential Biases

Potential bias may arise from the association of the DPYD polymorphism with specific tumor types.

Limitations

The study's sample size, while significant, is still limited, and further analysis with more cases is needed.

Participant Demographics

Caucasian cancer patients diagnosed with breast, gastroesophageal, and colorectal cancer.

Statistical Information

P-Value

p (corrected) = 0.001

Confidence Interval

95% CI 2.12–9.23

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1371/journal.pone.0004003

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