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Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea.


ABSTRACT: BACKGROUND/AIM:Afatinib, a 2nd 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).

SUBMITTER: Sogawa R 

PROVIDER: S-EPMC7279839 | biostudies-literature | 2020 May-Jun

REPOSITORIES: biostudies-literature

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Association of Genetic Polymorphisms With Afatinib-induced Diarrhoea.

Sogawa Rintaro R   Nakashima Chiho C   Nakamura Tomomi T   Takeuchi Koji K   Kimura Sakiko S   Komiya Kazutoshi K   Narisawa Yutaka Y   Kimura Shinya S   Sueoka-Aragane Naoko N  

In vivo (Athens, Greece) 20200501 3


<h4>Background/aim</h4>Afatinib, a 2<sup>nd</sup> 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.<h4>Patients and methods</h4>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  ...[more]

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