Geographic and age variations in mutational processes in colorectal cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F25%3A00644604" target="_blank" >RIV/67985904:_____/25:00644604 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61383082:_____/25:00001536 RIV/00216208:11110/25:10497396 RIV/00216208:11130/25:10497396 RIV/00064203:_____/25:10497396

Výsledek na webu

<a href="https://www.nature.com/articles/s41586-025-09025-8" target="_blank" >https://www.nature.com/articles/s41586-025-09025-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41586-025-09025-8" target="_blank" >10.1038/s41586-025-09025-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Geographic and age variations in mutational processes in colorectal cancer

Popis výsledku v původním jazyce

Incidence rates of colorectal cancer vary geographically and have changed over time1. Notably, in the past two decades, the incidence of early-onset colorectal cancer, which affects individuals below 50 years of age, has doubled in many countries2, 3, 4-5. The reasons for this increase are unknown. Here we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite-unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown aetiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin6,7, had higher mutation loads in countries with higher colorectal cancer incidence rates. SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals who were diagnosed before 40 years of age than in those over 70 years of age, and were imprinted early during colorectal cancer development. Colibactin exposure was further linked to APC driver mutations, with ID18 being responsible for about 25% of APC driver indels in colibactin-positive cases. This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that mutagenic exposure to colibactin-producing bacteria in early life may contribute to the increasing incidence of early-onset colorectal cancer.

Název v anglickém jazyce

Geographic and age variations in mutational processes in colorectal cancer

Popis výsledku anglicky

Incidence rates of colorectal cancer vary geographically and have changed over time1. Notably, in the past two decades, the incidence of early-onset colorectal cancer, which affects individuals below 50 years of age, has doubled in many countries2, 3, 4-5. The reasons for this increase are unknown. Here we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite-unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown aetiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin6,7, had higher mutation loads in countries with higher colorectal cancer incidence rates. SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals who were diagnosed before 40 years of age than in those over 70 years of age, and were imprinted early during colorectal cancer development. Colibactin exposure was further linked to APC driver mutations, with ID18 being responsible for about 25% of APC driver indels in colibactin-positive cases. This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that mutagenic exposure to colibactin-producing bacteria in early life may contribute to the increasing incidence of early-onset colorectal cancer.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

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

ISSN

0028-0836

e-ISSN

1476-4687

Svazek periodika

643

Číslo periodika v rámci svazku

8070

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

230-240

Kód UT WoS článku

001498133700001

EID výsledku v databázi Scopus

2-s2.0-105006901651