Risk of Incident Lung Cancer in Individuals With Clonal Hematopoiesis

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In a study reported in the Journal of Clinical Oncology, Tian et al found that clonal hematopoiesis was associated with an increased risk of subsequent lung cancer, independent of known risk factors.

Study Details

Two nested case-control studies were performed. One included 832 incident lung cancer cases and 3,951 controls without any cancer matched for year of blood draw, sex, race, and smoking status from among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing performed between 2006 and 2019. A second included 141 cases and 652 matched controls from among 27,975 participants in the Mass General Brigham Biobank (MGBB) with whole-exome sequencing performed between 2010 and 2021. An additional analysis compared prevalence of clonal hematopoiesis in published data from 5,003 patients with solid tumors (including 2,279 lung cancer cases) who had pretreatment blood sequencing performed in the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) program.

Key Findings

In the UKBB case-control study, presence of clonal hematopoiesis on initial testing was found in 12.5% of incident lung cancer cases vs 8.7% of controls (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.06–1.74). A strong association remained after adjustment for factors such as history of chronic obstructive pulmonary disease, polygenic risk score, and C-reactive protein level. The differences in clonal hematopoiesis prevalence between cases and controls was driven by expanded clonal hematopoiesis mutations with variant allele frequency (VAF) of ≥10% (OR = 1.63, 95% CI = 1.15–2.30), with no significant difference (OR = 1.17, 95% CI = 0.84–1.63) observed at VAF of 2% to < 10% (P for trend = .031).

In the MGBB case-control study, a similar enrichment of clonal hematopoiesis in incident lung cancer cases vs controls was observed (15.6% of cases vs 12.7% of controls; OR = 1.33, 95% CI = 0.82–2.14). In meta-analysis of the UKBB and MGBB studies, odds ratios for clonal hematopoiesis prevalence in cases vs controls were 1.35 (95% CI = 1.08–1.68) overall and 1.61 (95% CI = 1.19–2.18) for VAF ≥ 10%.

In the MSK-IMPACT analysis, adjusted for age, sex, and smoking status, pretreatment lung cancer was associated with a numerically higher prevalence of clonal hematopoiesis compared with breast (reference category), colorectal, prostate, and pancreatic cancers. No significant difference was observed between lung vs breast cancer overall (OR = 1.05, 95% CI = 0.82–1.33); however, a significant difference was observed for clonal hematopoiesis with VAF ≥ 10% (OR = 1.61, 95% CI = 1.03–2.53). Pretreatment prostate cancer was also significantly enriched for clonal hematopoiesis with VAF ≥ 10% vs breast cancer (OR = 1.84, 95% CI = 1.04–3.24).

The investigators concluded, “Independent of known risk factors, clonal hematopoiesis is associated with increased risk of lung cancer…. Clonal hematopoiesis may serve as a novel biomarker for lung cancer prevention and early detection. Future studies are warranted to elucidate the underlying mechanisms of this positive association.”

Yin Cao, ScD, MPH, of the Division of Public Health Sciences, Washington University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and the National Heart, Lung, and Blood Institute. For full disclosures of the study articles, visit

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