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[Detection of UGT1A1*28 Polymorphism Using Fragment Analysis].

Ying Huang1, Jian Su1, Xiaosui Huang1

  • 1Guangdong General Hospital Institute of Lung Cancer, Key Laboratory of Translational Medicine, Medical Research Center, 
Guangdong General Hospital Guangdong Academy of Medical Sciences, Guangzhou 510080, China.

Zhongguo Fei AI Za Zhi = Chinese Journal of Lung Cancer
|December 27, 2017
PubMed
Summary

A new fragment analysis method accurately detects UGT1A1*28 polymorphism, crucial for predicting irinotecan toxicity in cancer patients. This robust method is simple and efficient for clinical use.

Keywords:
Fragment analysisPolymorphismUGT1A1

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Area of Science:

  • Pharmacogenomics
  • Molecular diagnostics
  • Cancer therapy

Background:

  • Uridine-diphosphoglucuronosyl transferase 1A1 (UGT1A1) activity is vital for irinotecan metabolism.
  • The UGT1A1*28 polymorphism significantly reduces UGT1A1 enzymatic activity.
  • Reduced activity increases the risk of severe toxicities in patients receiving irinotecan.

Purpose of the Study:

  • To develop and validate a fragment analysis method for detecting the UGT1A1*28 polymorphism.
  • To assess the clinical utility of fragment analysis for UGT1A1*28 genotyping.

Main Methods:

  • Fragment analysis was employed to genotype the UGT1A1*28 polymorphism.
  • A total of 286 blood specimens from lung cancer patients were analyzed.
  • The method's precision and accuracy were compared against Sanger sequencing.

Main Results:

  • The fragment analysis method demonstrated 100% precision and accuracy compared to Sanger sequencing.
  • Genotyping results revealed TA6/6 in 82.5%, TA6/7 in 16.8%, and TA7/7 in 0.7% of the 286 patients.
  • The study successfully genotyped UGT1A1*28 in a cohort of lung cancer patients.

Conclusions:

  • Fragment analysis is a robust, simple, time-saving, and easily implementable method for UGT1A1*28 polymorphism detection in clinical settings.
  • This validated method supports personalized irinotecan therapy by identifying patients at risk of toxicity.
  • The findings advocate for the routine use of fragment analysis in clinical practice for pharmacogenetic testing.