Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea

Rintaro Sogawa; Chiho Nakashima; Tomomi Nakamura; Koji Takeuchi; Sakiko Kimura; Kazutoshi Komiya; Yutaka Narisawa; Shinya Kimura; Naoko Sueoka-Aragane

doi:10.21873/invivo.11922

Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea

In Vivo. 2020 May-Jun;34(3):1415-1419. doi: 10.21873/invivo.11922.

Authors

Rintaro Sogawa¹, Chiho Nakashima², Tomomi Nakamura², Koji Takeuchi³, Sakiko Kimura³, Kazutoshi Komiya², Yutaka Narisawa³, Shinya Kimura², Naoko Sueoka-Aragane^{3

2}

Affiliations

¹ Department of Pharmacy, Saga University Hospital, Saga, Japan sogawari@cc.saga-u.ac.jp.
² Division of Haematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
³ Department of Pharmacy, Saga University Hospital, Saga, Japan.

Abstract

Background/aim: Afatinib, a 2^nd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used in treatment of non-small cell lung cancer (NSCLC), causes diarrhoea in over 90% of patients. The association of genetic background with diarrhoea is poorly understood.

Patients and methods: We evaluated the roles of four single nucleotide polymorphisms (SNPs) in ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily G member 2 (ABCG2) genes-ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T, and ABCG2 421 C>A-on treatment-induced diarrhoea in 38 patients with NSCLC treated with afatinib.

Results: Diarrhoea occurred more frequently in patients with ABCB1 2677 T(A)/T(A) (14/16, 87.5%) than in patients with non-T(A)/T(A) alleles (8/22, 36.4%) (p=0.003). ABCB1 2677 T(A)/T(A) was significantly predictive of diarrhoea (p=0.002) by multivariable regression analysis.

Conclusion: Afatinib-induced diarrhoea is associated with the SNP ABCB1 2677 T(A)/T(A).

Keywords: ABCB1; Afatinib; diarrhoea; genetic polymorphism.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
Afatinib / adverse effects*
Afatinib / therapeutic use
Aged
Aged, 80 and over
Antineoplastic Agents / adverse effects*
Antineoplastic Agents / therapeutic use
Diarrhea / diagnosis
Diarrhea / etiology*
Female
Genetic Predisposition to Disease*
Humans
Incidence
Male
Middle Aged
Neoplasm Proteins / genetics
Odds Ratio
Polymorphism, Single Nucleotide*
Protein Kinase Inhibitors / adverse effects*
Protein Kinase Inhibitors / therapeutic use

Substances

ABCB1 protein, human
ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily G, Member 2
Antineoplastic Agents
Neoplasm Proteins
Protein Kinase Inhibitors
Afatinib