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Clonal Hematopoiesis and Risk of Incident Lung Cancer

Tian, Ruiyi ; Wiley, Brian ; Liu, Jie ; Zong, Xiaoyu ; Truong, Buu ; Zhao, Stephanie ; Uddin, Md Mesbah ; Niroula, Abhishek LU ; Miller, Christopher A. and Mukherjee, Semanti , et al. (2023) In Journal of clinical oncology : official journal of the American Society of Clinical Oncology 41(7). p.1423-1433
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
in
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
volume
41
issue
7
pages
11 pages
publisher
American Society of Clinical Oncology
external identifiers
  • pmid:36480766
  • scopus:85148965026
ISSN
0732-183X
DOI
10.1200/JCO.22.00857
language
English
LU publication?
yes
id
29a338b0-5230-48cd-92ef-f43eb2d8670e
date added to LUP
2023-03-15 10:57:55
date last changed
2024-06-13 10:56:02
@article{29a338b0-5230-48cd-92ef-f43eb2d8670e,
  abstract     = {{<p>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.</p>}},
  author       = {{Tian, Ruiyi and Wiley, Brian and Liu, Jie and Zong, Xiaoyu and Truong, Buu and Zhao, Stephanie and Uddin, Md Mesbah and Niroula, Abhishek and Miller, Christopher A. and Mukherjee, Semanti and Heiden, Brendan T. and Luo, Jingqin and Puri, Varun and Kozower, Benjamin D. and Walter, Matthew J. and Ding, Li and Link, Daniel C. and Amos, Christopher I. and Ebert, Benjamin L. and Govindan, Ramaswamy and Natarajan, Pradeep and Bolton, Kelly L. and Cao, Yin}},
  issn         = {{0732-183X}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{7}},
  pages        = {{1423--1433}},
  publisher    = {{American Society of Clinical Oncology}},
  series       = {{Journal of clinical oncology : official journal of the American Society of Clinical Oncology}},
  title        = {{Clonal Hematopoiesis and Risk of Incident Lung Cancer}},
  url          = {{http://dx.doi.org/10.1200/JCO.22.00857}},
  doi          = {{10.1200/JCO.22.00857}},
  volume       = {{41}},
  year         = {{2023}},
}