Clonal Hematopoiesis Mutations in Patients with Lung Cancer Are Associated with Lung Cancer Risk Factors
| Autor: | Xiangjun Xiao, James McKay, Yanhong Liu, David C. Christiani, Rayjean J. Hung, Chao Cheng, Wei Hong, John K. Field, Ang Li, Christopher I. Amos |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cancer Research Lung Neoplasms Biology Polymorphism Single Nucleotide Article Risk Factors Exome Sequencing medicine Humans SNP Family history Risk factor Medical History Taking Lung cancer Aged Retrospective Studies Genetic association Aged 80 and over Smoking Age Factors Hematopoietic stem cell Promoter Middle Aged medicine.disease Leukemia medicine.anatomical_structure Oncology Case-Control Studies Mutation Cancer research Female Ubiquitin-Specific Proteases Clonal Hematopoiesis |
| Zdroj: | Cancer Res |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. Significance: Analysis of whole-exome sequencing data uncovers correlations between clonal hematopoiesis and lung cancer risk factors, identifies genetic variants correlated with clonal hematopoiesis, and highlights hundreds of potential novel clonal hematopoiesis mutations. |
| Databáze: | OpenAIRE |
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