Clonal Hematopoiesis and Risk of Incident Lung Cancer.
J Clin Oncol
; 41(7): 1423-1433, 2023 03 01.
Article
en En
| MEDLINE
| ID: mdl-36480766
ABSTRACT
PURPOSE:
To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer.METHODS:
Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets.RESULTS:
In UKBB, the presence of CH was associated with increased risk of lung cancer (cases 12.5% v controls 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases 15.6% v controls 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung v breast cancer 1.61; 95% CI, 1.03 to 2.53).CONCLUSION:
Independent of known risk factors, CH is associated with increased risk of lung cancer.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hematopoyesis Clonal
/
Neoplasias Pulmonares
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Clin Oncol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Macao