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Influence of UGT1A1 *6/*28 Polymorphisms on Irinotecan-Related Toxicity and Survival in Pediatric Patients with

Xiaoqin Zhu1,2, Jia Zhu1,2, Feifei Sun1,2

  • 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

Pharmacogenomics and Personalized Medicine
|April 1, 2021
PubMed

Insights

The UGT1A1*6 gene variant increases irinotecan toxicity like diarrhea and anemia in children with solid tumors. UGT1A1*28 may offer protection, but both variants might impact survival, requiring further study.

Area of Science:

  • Pharmacogenomics
  • Pediatric Oncology

Background:

  • Irinotecan is a key chemotherapy for pediatric solid tumors.
  • UGT1A1 gene polymorphisms (UGT1A1*6, UGT1A1*28) affect irinotecan metabolism.
  • The impact of these polymorphisms on pediatric treatment outcomes is not well-established.

Purpose of the Study:

  • To investigate the association between UGT1A1*6/*28 polymorphisms and irinotecan toxicity in pediatric patients.
  • To evaluate the influence of these polymorphisms on survival rates in children with relapsed/refractory solid tumors.

Main Methods:

  • Retrospective study of 44 pediatric patients (<18 years) treated between 2014-2017.
  • Analysis of UGT1A1*6 and UGT1A1*28 genotypes.
  • Correlation of genotypes with irinotecan-related toxicities (diarrhea, anemia) and overall survival.

Main Results:

  • UGT1A1*6 polymorphism was linked to increased risk of grade I-IV diarrhea (P=0.043) and anemia (P=0.002).
  • UGT1A1*28 polymorphism showed a potential protective effect against irinotecan-related diarrhea and abdominal pain.
  • Neither polymorphism was associated with severe (grade III-IV) toxicities, but both showed a trend towards reduced overall survival.

Conclusions:

  • UGT1A1*6 acts as a risk factor for specific irinotecan toxicities in pediatric solid tumors.
  • UGT1A1*28 may offer a protective role against certain irinotecan side effects.
  • Both polymorphisms warrant further investigation as potential risk factors for survival in this population.
Abstract

Keywords:
UGT1A1 *6/*28 polymorphismirinotecan toxicitypediatricrelapsed/refractory solid tumors

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