Clonal Hematopoiesis Mutations in Lung Cancer Patients are Associated with Lung Cancer Risk Factors.

Hong, Wei, Li, Ang, Liu, Yanhong, Xiao, Xiangjun, Christiani, David C, Hung, Rayjean J, McKay, James, Field, John ORCID: 0000-0003-3951-6365, Amos, Christopher I and Cheng, Chao (2021) Clonal Hematopoiesis Mutations in Lung Cancer Patients are Associated with Lung Cancer Risk Factors. Cancer research, 82 (2). pp. 199-209.

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Official URL: http://dx.doi.org/10.1158/0008-5472.can-21-1903

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 OTUD3. Hundreds of potentially novel CH mutations were identified, and smoking was found to potentially shape the CH mutational signature. Genetic variants and lung cancer risk factors, especially FHLC, correlated with CH. These analyses improve our understanding of the relationship between lung cancer and CH, and future experimental studies will be necessary to corroborate the uncovered correlations.

Item Type:	Article
Uncontrolled Keywords:	Humans, Lung Neoplasms, Medical History Taking, Risk Factors, Case-Control Studies, Retrospective Studies, Smoking, Age Factors, Mutation, Polymorphism, Single Nucleotide, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Ubiquitin-Specific Proteases, Clonal Hematopoiesis, Exome Sequencing
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	20 Dec 2021 08:17
Last Modified:	25 Jan 2023 14:07
DOI:	10.1158/0008-5472.can-21-1903
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3145616