Publication Date
1-15-2022
Journal
Cancer Research
DOI
10.1158/0008-5472.CAN-21-1903
PMID
34815255
PMCID
PMC8815061
PubMedCentral® Posted Date
11-23-2021
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Adult, Age Factors, Aged, Aged, 80 and over, Case-Control Studies, Clonal Hematopoiesis, Female, Humans, Lung Neoplasms, Male, Medical History Taking, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Retrospective Studies, Risk Factors, Smoking, Ubiquitin-Specific Proteases, Exome Sequencing
Abstract
Clonal hematopoiesis (CH) is a phenomenon caused by expansion of white blood cells descended from a single hematopoietic stem cell. While CH can be associated with leukemia and some solid tumors, the relationship between CH and lung cancer remains largely unknown. To help clarify this relationship, we analyzed whole-exome sequencing (WES) data from 1,958 lung cancer cases and controls. Potential CH mutations were identified by a set of hierarchical filtering criteria in different exonic regions, and the associations between the number of CH mutations and clinical traits were investigated. Family history of lung cancer (FHLC) may exert diverse influences on the accumulation of CH mutations in different age groups. In younger subjects, FHLC was the strongest risk factor for CH mutations. Association analysis of genome-wide genetic variants identified dozens of genetic loci associated with CH mutations, including a candidate SNP rs2298110, which may promote CH by increasing expression of a potential leukemia promoter gene
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