Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F19%3A00012661" target="_blank" >RIV/75010330:_____/19:00012661 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0041008X19302212?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0041008X19302212?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.taap.2019.114619" target="_blank" >10.1016/j.taap.2019.114619</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol

Popis výsledku v původním jazyce

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytothrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with ClOOT substitution encode null or poor functional proteins. This study aims to examine the association of ClOOT 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 ClOOT 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-hydrmrytarnoxifen or endoxifen levels. Results indicate that ClOOT 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.

Název v anglickém jazyce

Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol

Popis výsledku anglicky

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytothrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with ClOOT substitution encode null or poor functional proteins. This study aims to examine the association of ClOOT 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 ClOOT 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-hydrmrytarnoxifen or endoxifen levels. Results indicate that ClOOT 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV17-28470A" target="_blank" >NV17-28470A: Význam markerů oxysterolové dráhy pro hormonální terapii karcinomu prsu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Toxicology and Applied Pharmacology

ISSN

0041-008X

e-ISSN

1096-0333

Svazek periodika

378

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

114619

Kód UT WoS článku

000477917100013

EID výsledku v databázi Scopus

2-s2.0-85067983507