Personalized Medicine in Infant Population with Cancer: Pharmacogenetic Pilot Study of Polymorphisms Related to Toxicity and Response to Chemotherapy.

Fecha de publicación: 23/02/2023 Fecha Ahead of Print: 23/02/2023

Autores de IIS La Fe

• Luis Sendra Gisbert

  Autor

• Pablo Berlanga Charriel

  Autor

• Pablo Gargallo Tatay

  Autor

• David Hervás Marín

  Autor

• Julia Balaguer Guill

  Autor

• Antonio Juan Ribelles

  Autor

• Adela Cañete Nieto

  Autor

• María José Herrero Cervera

  Autor

Participantes ajenos a IIS La Fe

• Urtasun, Andrea
• Olivera, Gladys G.
• Alino, Salvador F.
• Andres, Maria del Mar

Grupos

• Farmacogenética

  Investigador Principal

  María José Herrero Cervera

• Investigación Clínica y Traslacional en Cáncer

  

  Leader

  José Gómez Codina

Abstract

BACKGROUND: Pharmacogenetics is a personalized medicine tool that aims to optimize treatments by adapting them to each individual's genetics, maximizing their efficacy while minimizing their toxicity. Infants with cancer are especially vulnerable, and their co-morbidities have vital repercussions. The study of their pharmacogenetics is new in this clinical field. METHODS: A unicentric, ambispective study of a cohort of infants receiving chemotherapy (from January 2007 to August 2019). The genotypes of 64 patients under 18 months of age were correlated with severe drug toxicities and survival. A pharmacogenetics panel was configured based on PharmGKB, drug labels, and international experts' consortiums. RESULTS: Associations between SNPs and hematological toxicity were found. Most meaningful were: MTHFR rs1801131 GT increasing the anemia risk (OR 1.73); rs1517114 GC, XPC rs2228001 GT, increasing neutropenia risk (OR 1.50 and 4.63); ABCB1 rs1045642 AG, TNFRSF11B rs2073618 GG, CYP2B6 rs4802101 TC and SOD2 rs4880 GG increasing thrombocytopenia risk (OR 1.70, 1.77, 1.70, 1.73, respectively). Regarding survival, MTHFR rs1801133 GG, TNFRSF11B rs2073618 GG, XPC rs2228001 GT, CYP3A4 rs2740574 CT, CDA rs3215400 del.del, and SLC01B1 rs4149015 GA were associated with lower overall survival probabilities (HR 3.12, 1.84, 1.68, 2.92, 1.90, and 3.96, respectively). Lastly, for event-free survival, SLC19A1 rs1051266 TT and CDA rs3215400 del.del increased the relapse probability (HR 1.61 and 2.19, respectively). CONCLUSIONS: This pharmacogenetic study is a pioneer in dealing with infants under 18 months of age. Further studies are needed to confirm the utility of the findings in this work to be used as predictive genetic biomarkers of toxicity and therapeutic efficacy in the infant population. If confirmed, their use in therapeutic decisions could improve the quality of life and prognosis of these patients.

Keywords

• SNP (single nucleotide polymorphism); anemia; chemotherapy; event-free survival; infant; neutropenia; overall survival; pharmacogenetics; therapeutic efficacy; thrombocytopenia; toxicity