| Title: | Clonal Hematopoiesis and Risk of Incident Lung Cancer |
| Journal: | Journal of Clinical Oncology |
| Published: | 8 Dec 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36480766/ |
| DOI: | https://doi.org/10.1200/jco.22.00857 |
Publication 10794
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Abstract
PURPOSE: To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer.</p>
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.</p>
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).</p>
CONCLUSION: Independent of known risk factors, CH is associated with increased risk of lung cancer.</p>
23 Authors
- Ruiyi Tian
- Brian Wiley
- Jie Liu
- Xiaoyu Zong
- Buu Truong
- Stephanie Zhao
- 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 Govindan
- Pradeep Natarajan
- Kelly L. Bolton
- Yin Cao
1 Application
| Application ID | Title |
|---|---|
| 55288 | Early life, adulthood, and genomic risk factors for early-onset cancers |
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