Clonal Hematopoiesis and Risk of Incident Lung Cancer

Ruiyi Tian, Brian Wiley, Jie Liu, Xiaoyu Zong, Buu Truong, Stephanie Zhao, Md Mesbah Uddin, Abhishek Niroula, Christopher A. Miller, Semanti Mukherjee, Brendan T. Heiden, Jingqin Luo, Varun Puri, Benjamin D. Kozower, Matthew J. Walter, Li Ding, Daniel C. Link, Christopher I. Amos, Benjamin L. Ebert, Ramaswamy GovindanPradeep Natarajan, Kelly L. Bolton, Yin Cao

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1423-1433
Number of pages11
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume41
Issue number7
DOIs
Publication statusPublished - 2023 Mar 1

Subject classification (UKÄ)

  • Cancer and Oncology

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