Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol
2024

Genetic Variants Affecting Chemotherapy Response in Osteosarcoma

Sample size: 69 publication 10 minutes Evidence: moderate

Author Information

Author(s): Juliana Salazar, María J. Arranz, Javier Martin-Broto, Francisco Bautista, Jerónimo Martínez-García, Javier Martínez-Trufero, Yolanda Vidal-Insua, Aizpea Echebarria-Barona, Roberto Díaz-Beveridge, Claudia Valverde, Pablo Luna, María A. Vaz-Salgado, Pilar Blay, Rosa Álvarez, Ana Sebio, Dragoi Cristina Manuela

Primary Institution: Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain

Hypothesis

Can genetic variants in DNA repair and drug metabolism pathways predict response to MAP chemotherapy in osteosarcoma patients?

Conclusion

Genetic variants in the ABCC2 and ERCC2 genes are associated with poor pathological response to chemotherapy, while variants in ABCB1 and ABCC3 are linked to severe hepatotoxicity.

Supporting Evidence

  • 26 patients achieved a good pathological response (≥90%) after chemotherapy.
  • ABCC2 rs2273697 and ERCC2 rs1799793 variants were associated with poor pathological response.
  • ABCB1 rs1128503 and ABCC3 rs4793665 variants were linked to severe hepatotoxicity.

Takeaway

Some people have different genes that can make their cancer treatment work better or worse. This study found specific genes that might help doctors choose the best treatment for kids with bone cancer.

Methodology

Germline polymorphisms in specific genes were analyzed in 69 patients with localized osteosarcoma enrolled in the GEIS-33 trial.

Potential Biases

Potential bias due to the small sample size and the exploratory nature of the study.

Limitations

The sample size is small due to the rarity of osteosarcoma, and not all safety data were available for all patients.

Participant Demographics

Patients aged 4 to 32 years, with a median age of 14 years; 46.4% female and 53.6% male.

Statistical Information

P-Value

0.003

Confidence Interval

95% CI 2.1–66.2 for ABCC2 rs2273697; 95% CI 2.1–70.2 for ABCC3 rs4793665

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.3390/pharmaceutics16121585

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