DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10469588" target="_blank" >RIV/00064165:_____/23:10469588 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/23:10469588 RIV/00064211:_____/23:W0000009

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1CGjORV79E" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1CGjORV79E</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41698-023-00452-2" target="_blank" >10.1038/s41698-023-00452-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment

Popis výsledku v původním jazyce

To individualise breast cancer (BC) prevention, markers to follow a person&apos;s changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID (TM)-qtBC index, can identify women with breast cancer in hormone-sensitive tissues (AUC = 0.71 [95% CI: 0.65-0.77] in cervical samples). Women in the highest combined risk group (high polygenic risk score and WID (TM)-qtBC) had a 9.6-fold increased risk for BC [95% CI: 4.7-21] compared to the low-risk group and tended to present at more advanced stages. Importantly, the WID (TM)-qtBC is influenced by non-genetic BC risk factors, including age and body mass index, and can be modified by a preventive pharmacological intervention, indicating an interaction between genome and environment recorded at the level of the epigenome. Our findings indicate that methylation levels at mQTLs in relevant surrogate tissues could enable integration of heritable and non-heritable factors for improved disease risk stratification.

Název v anglickém jazyce

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment

Popis výsledku anglicky

To individualise breast cancer (BC) prevention, markers to follow a person&apos;s changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID (TM)-qtBC index, can identify women with breast cancer in hormone-sensitive tissues (AUC = 0.71 [95% CI: 0.65-0.77] in cervical samples). Women in the highest combined risk group (high polygenic risk score and WID (TM)-qtBC) had a 9.6-fold increased risk for BC [95% CI: 4.7-21] compared to the low-risk group and tended to present at more advanced stages. Importantly, the WID (TM)-qtBC is influenced by non-genetic BC risk factors, including age and body mass index, and can be modified by a preventive pharmacological intervention, indicating an interaction between genome and environment recorded at the level of the epigenome. Our findings indicate that methylation levels at mQTLs in relevant surrogate tissues could enable integration of heritable and non-heritable factors for improved disease risk stratification.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

npj Precision Oncology

ISSN

2397-768X

e-ISSN

2397-768X

Svazek periodika

7

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

99

Kód UT WoS článku

001074904600001

EID výsledku v databázi Scopus

2-s2.0-85173114926