The following is a summary of “Clonal Hematopoiesis and Risk of Incident Lung Cancer,” published in the March 2023 issue of Oncology by Tian, et al.

For a study, researchers sought to investigate the association between clonal hematopoiesis (CH) and the subsequent risk of lung cancer. 

The study analyzed 200,629 UK Biobank (UKBB) participants with whole-exome sequencing and identified CH in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (matched on age and year at blood draw, sex, race, and smoking status) from 2006 to 2019. 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 (2010-2021). In addition, the study compared CH frequency in published data from 5,003 patients with solid tumors (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets.

The results showed that the presence of CH was associated with a significantly increased risk of lung cancer in UKBB (cases: 12.5% v controls: 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained significant after excluding participants with chronic obstructive pulmonary disease, and no significant interactions with known risk factors were identified. Similar enrichment of CH in lung cancer (cases: 15.6% v controls: 12.7%) was observed in MGBB, and 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 addition, the study found that 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).

In conclusion, the study found that clonal hematopoiesis (CH) is independently associated with an increased risk of lung cancer, even after adjusting for known risk factors. The study provided important insights into the potential use of CH as a biomarker for lung cancer risk.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00857