Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10497206" target="_blank" >RIV/00064165:_____/25:10497206 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10497206

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rP693z_H4G" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=rP693z_H4G</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41431-025-01786-0" target="_blank" >10.1038/s41431-025-01786-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer

Popis výsledku v původním jazyce

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

Název v anglickém jazyce

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer

Popis výsledku anglicky

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which were associated with non-high-grade serous ovarian cancer and MIGA1 which was associated with high-grade serous ovarian cancer. Further support for the association of HELB association comes from the observation that loss-of-function variants in HELB are associated with age at natural menopause and Mendelian randomisation analysis shows an association between genetically predicted age at natural menopause and endometrioid ovarian cancer, but not high-grade serous ovarian cancer.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

European Journal of Human Genetics

ISSN

1018-4813

e-ISSN

1476-5438

Svazek periodika

33

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

297-303

Kód UT WoS článku

001418909500001

EID výsledku v databázi Scopus

2-s2.0-85218227971