Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2: Risk Estimation and Clinical Recommendations in East Asia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00638798" target="_blank" >RIV/68378050:_____/25:00638798 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10501710 RIV/00064165:_____/25:10501710

Výsledek na webu

<a href="https://doi.org/10.1200/PO-24-00945" target="_blank" >https://doi.org/10.1200/PO-24-00945</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1200/PO-24-00945" target="_blank" >10.1200/PO-24-00945</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2: Risk Estimation and Clinical Recommendations in East Asia

Popis výsledku v původním jazyce

PURPOSECHEK2 is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clinical relevance of germline variants differs across population, there is little evidence of the clinical relevance of CHEK2 germline variants in East Asia.METHODSTargeted sequencing and functional analyses of missense variants for the coding region of CHEK2 in 111,571 East Asian individuals were performed. Variants classified as pathogenic/likely pathogenic in ClinVar, predicted loss-of-function, or functionally impaired in functional analysis were defined as germline damaging variants (gDVs). We evaluated the association between CHEK2 gDVs and the risk of 23 cancer types. We also compared the clinical characteristics of carriers and noncarriers among patients with CHEK2-associated cancers.RESULTSWe identified 77 gDVs including 36 functionally impaired missense variants. CHEK2 gDVs were significantly associated exclusively with prostate cancer (odds ratio [OR], 1.8 [95% CI, 1.2 to 2.6],P = 1.7 x 10-3), in addition to female breast cancer (OR, 1.8 [95% CI, 1.3 to 2.6], P = 1.2 x 10-3), among 23 cancer types. There were no differences in age at diagnosis, pathologic status, and prognosis between carriers and noncarriers. Besides, there was no association with the risk of cancer types with high incidence rates in East Asian countries.CONCLUSIONCHEK2 gDVs were associated with female breast and prostate cancer risks in East Asia. The necessity of additional systematic clinical management for all CHEK2 gDV carriers should be carefully discussed, and standard cancer screening is recommended unless no other clinical features suggestive of cancer predisposition are noted in East Asia.

Název v anglickém jazyce

Case-Control Study for 23 Cancer Types With Functional Analysis of CHEK2: Risk Estimation and Clinical Recommendations in East Asia

Popis výsledku anglicky

PURPOSECHEK2 is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clinical relevance of germline variants differs across population, there is little evidence of the clinical relevance of CHEK2 germline variants in East Asia.METHODSTargeted sequencing and functional analyses of missense variants for the coding region of CHEK2 in 111,571 East Asian individuals were performed. Variants classified as pathogenic/likely pathogenic in ClinVar, predicted loss-of-function, or functionally impaired in functional analysis were defined as germline damaging variants (gDVs). We evaluated the association between CHEK2 gDVs and the risk of 23 cancer types. We also compared the clinical characteristics of carriers and noncarriers among patients with CHEK2-associated cancers.RESULTSWe identified 77 gDVs including 36 functionally impaired missense variants. CHEK2 gDVs were significantly associated exclusively with prostate cancer (odds ratio [OR], 1.8 [95% CI, 1.2 to 2.6],P = 1.7 x 10-3), in addition to female breast cancer (OR, 1.8 [95% CI, 1.3 to 2.6], P = 1.2 x 10-3), among 23 cancer types. There were no differences in age at diagnosis, pathologic status, and prognosis between carriers and noncarriers. Besides, there was no association with the risk of cancer types with high incidence rates in East Asian countries.CONCLUSIONCHEK2 gDVs were associated with female breast and prostate cancer risks in East Asia. The necessity of additional systematic clinical management for all CHEK2 gDV carriers should be carefully discussed, and standard cancer screening is recommended unless no other clinical features suggestive of cancer predisposition are noted in East Asia.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

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

JCO Precision Oncology

ISSN

2473-4284

e-ISSN

2473-4284

Svazek periodika

9

Číslo periodika v rámci svazku

Sep 02

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

e2400945

Kód UT WoS článku

001562439000001

EID výsledku v databázi Scopus

2-s2.0-105015566703