Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea.

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.