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Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol
TC. Chao, WC. Pan, YF. Tsai, YC. Chou, YR. Liu, SF. Wang, YJ. Chen, P. Souček, YF. Ueng,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NV17-28470A
MZ0
CEP - Centrální evidence projektů
- MeSH
- cholesterol krev MeSH
- cytochrom P-450 CYP2D6 metabolismus MeSH
- dospělí MeSH
- fenotyp MeSH
- genotyp MeSH
- hormonální protinádorové látky krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu krev metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tamoxifen analogy a deriváty krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.
Chang Gung University College of Medicine Taoyuan City Taiwan
Department of Oncology Taipei Veterans General Hospital Taipei Taiwan
Department of Pharmacy Taipei Veterans General Hospital Taipei Taiwan
Department of Surgery Taipei Veterans General Hospital Taipei Taiwan
Department of Toxicogenomics National Institute of Public Health Prague Czech Republic
Institute of Medical Sciences Taipei Medical University Taipei Taiwan
National Research Institute of Chinese Medicine Taipei Taiwan
Citace poskytuje Crossref.org
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- $a Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.
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- $a Ueng, Yune-Fang $u National Research Institute of Chinese Medicine, Taipei, Taiwan; Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Biopharmaceutical Sciences, School of Pharmacy, National Yang-Ming University, Taipei, Taiwan; Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. Electronic address: ueng@nricm.edu.tw.
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