Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea

Rintaro Sogawa1, Chiho Nakashima2, Tomomi Nakamura2

  • 1Department of Pharmacy, Saga University Hospital, Saga, Japan sogawari@cc.saga-u.ac.jp.

Abstract

Insights

Afatinib-induced diarrhea in non-small cell lung cancer patients is linked to a specific genetic variation. The ABCB1 2677 T(A)/T(A) single nucleotide polymorphism (SNP) significantly predicts this common side effect.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Afatinib is a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used for non-small cell lung cancer (NSCLC).
  • Diarrhea affects over 90% of patients treated with afatinib.
  • The genetic factors influencing afatinib-induced diarrhea are not well understood.

Purpose of the Study:

  • To investigate the association between genetic variations in ABCB1 and ABCG2 genes and afatinib-induced diarrhea in NSCLC patients.
  • To identify specific single nucleotide polymorphisms (SNPs) that predict the occurrence of diarrhea.

Main Methods:

  • The study analyzed four SNPs in the ABCB1 and ABCG2 genes: ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and ABCG2 421 C>A.
  • Genetic analysis was performed on 38 NSCLC patients treated with afatinib.
  • Multivariable regression analysis was used to determine predictive values of SNPs for diarrhea.

Main Results:

  • Diarrhea was more frequent in patients with the ABCB1 2677 T(A)/T(A) genotype (87.5%) compared to those with other alleles (36.4%).
  • The ABCB1 2677 T(A)/T(A) genotype was a significant predictor of afatinib-induced diarrhea (p=0.002).

Conclusions:

  • The single nucleotide polymorphism ABCB1 2677 T(A)/T(A) is associated with afatinib-induced diarrhea in NSCLC patients.
  • This finding contributes to understanding the pharmacogenetic basis of afatinib side effects.

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