Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10503660" target="_blank" >RIV/00064203:_____/25:10503660 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10503660 RIV/00216208:11130/25:10503660

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=tD95QE._Bf" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=tD95QE._Bf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-025-63842-z" target="_blank" >10.1038/s41467-025-63842-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites

Popis výsledku v původním jazyce

Head and neck squamous cell carcinoma (HNSCC) includes diverse cancers arising in the oral cavity, oropharynx, and larynx, with the main risk factors being environmental exposures such as tobacco, alcohol, and human papillomavirus (HPV) infection. The genetic factors contributing to susceptibility across different populations and tumour subsites remain incompletely understood. Here we show, through a genome-wide association and fine mapping study of over 19,000 HNSCC cases and 38,000 controls from multiple ancestries, 18 genetic risk variants and 11 signals from fine mapping of the human leukocyte antigen (HLA) region, all previously unreported. rs78378222, a regulatory variant for TP53 is associated with a 40% reduction in overall HNSCC risk. We also identify gene-environment interactions, with BRCA2 and ADH1B variants showing effects modified by smoking and alcohol use. Subsite-specific analysis of the HLA region reveals distinct immune-related associations across HPV-positive and HPV-negative tumours. These findings refine the genetic architecture of HNSCC and highlight mechanisms linking inherited variation, immunity, and environmental exposures.

Název v anglickém jazyce

Cross-ancestral GWAS identifies 29 variants across head and neck cancer subsites

Popis výsledku anglicky

Head and neck squamous cell carcinoma (HNSCC) includes diverse cancers arising in the oral cavity, oropharynx, and larynx, with the main risk factors being environmental exposures such as tobacco, alcohol, and human papillomavirus (HPV) infection. The genetic factors contributing to susceptibility across different populations and tumour subsites remain incompletely understood. Here we show, through a genome-wide association and fine mapping study of over 19,000 HNSCC cases and 38,000 controls from multiple ancestries, 18 genetic risk variants and 11 signals from fine mapping of the human leukocyte antigen (HLA) region, all previously unreported. rs78378222, a regulatory variant for TP53 is associated with a 40% reduction in overall HNSCC risk. We also identify gene-environment interactions, with BRCA2 and ADH1B variants showing effects modified by smoking and alcohol use. Subsite-specific analysis of the HLA region reveals distinct immune-related associations across HPV-positive and HPV-negative tumours. These findings refine the genetic architecture of HNSCC and highlight mechanisms linking inherited variation, immunity, and environmental exposures.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30206 - Otorhinolaryngology

Projekt

—

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

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

8787

Kód UT WoS článku

001586994200010

EID výsledku v databázi Scopus

2-s2.0-105017709035