Clonal Hematopoiesis and Risk of Incident Lung Cancer. Issue 7 (1st March 2023)

• Record Type: Journal Article
• Authors: Tian, Ruiyi; Wiley, Brian; Liu, Jie; Zong, Xiaoyu; Truong, Buu; Zhao, Stephanie; Uddin, Md Mesbah; Niroula, Abhishek; Miller, Christopher A.; Mukherjee, Semanti; Heiden, Brendan T.; Luo, Jingqin; Puri, Varun; Kozower, Benjamin D.; Walter, Matthew J.; Ding, Li; Link, Daniel C.; Amos, Christopher I.; Ebert, Benjamin L.; Govindan, Ramaswamy; Natarajan, Pradeep; Bolton, Kelly L.; Cao, Yin
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 7(2023)
• Page Start: 1423
• Page End: 1433
• Publication Date: 2023-03-01
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.22.00857
• Languages: English
• ISSNs: 0732-183X

Abstract

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.