CYP2D6*3 (A2549del), *4 (G1846A), *10 (C100T) and *17 (C1023T) genetic polymorphisms in Iranian breast cancer patients treated with adjuvant tamoxifen

Saghafi,Fatemeh; Salehifar,Ebrahim; Janbabai,Ghasem; Zaboli,Ehsan; Hedayatizadeh‑Omran,Akbar; Amjadi,Omolbanin; Moradi,Siavash

doi:10.3892/br.2018.1145

CYP2D63 (A2549del), 4 (G1846A), 10 (C100T) and 17 (C1023T) genetic polymorphisms in Iranian breast cancer patients treated with adjuvant tamoxifen

Authors:
- Fatemeh Saghafi
- Ebrahim Salehifar
- Ghasem Janbabai
- Ehsan Zaboli
- Akbar Hedayatizadeh‑Omran
- Omolbanin Amjadi
- Siavash Moradi
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Affiliations: Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari 48471‑16548, Iran, Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48471‑16548, Iran, Department of Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48471‑16548, Iran, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari 48166‑33131, Iran
Published online on: September 7, 2018 https://doi.org/10.3892/br.2018.1145
Pages: 446-452

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Abstract

There is controversy regarding the efficacy of tamoxifen in breast cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene polymorphisms. Poor metabolizer genotypes may not fully convert tamoxifen to its active metabolite endoxifen and thus have less exposure to anti‑estrogen therapy. The present study was conducted to identify the prevalence of CYP2D6 genotypes among Iranian breast cancer patients. A total of 84 estrogen receptor‑positive breast cancer patients treated at a referral center in the north of Iran were examined. A peripheral blood sample was obtained from each patient to determine the presence of *3, *4, *10 and *17 single nucleotide polymorphisms of the CYP2D6 gene by polymerase chain reaction‑based restriction fragment‑length polymorphism analysis. Of the four genotypes assessed, CYP2D6*4 was the most common variant and was identified in 41 (48.8%) patients as heterozygous (G/A) and 3 (3.6%) as homozygous (A/A) alleles. CYP2D6*10 heterozygous mutated alleles (C/T) were also a common genotype that presented in 22 (26.2%) of the study subjects. Variant *17 was less common and was detected only as heterozygous (C/T) in 3 patients (3.6%). No CYP2D6*3 heterozygous or homozygous mutated alleles were observed. In conclusion, the frequency of the CYP2D6 nonfunctional alleles *4 and *10 appeared relatively high in Iranian patients with hormone‑sensitive breast cancer. This finding may affect the selection of an optimal hormone therapy, as patients with low CYP2D6 pathway activity may not sufficiently convert tamoxifen to its active metabolite endoxifen.

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