WCLC 2025 - Posters & ePosters-EP.06.65 Mosaic Chromosomal Alterations and the Risk of Incident Lung Cancer: A Systematic Review and Meta-Analysis

EP.06.65 Mosaic Chromosomal Alterations and the Risk of Incident Lung Cancer: A Systematic Review and Meta-Analysis

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This systematic review and meta-analysis evaluated the association between mosaic chromosomal alterations (mCA) and the risk of incident lung cancer. Mosaic chromosomal alterations are somatic changes in peripheral blood leukocytes involving large chromosomal losses, gains, or copy-neutral loss of heterozygosity, with prevalence increasing with age and established links to hematologic cancers. However, their relationship with lung cancer risk has been unclear.<br /><br />The authors identified relevant cohort studies comparing lung cancer incidence in individuals with and without mCA from Embase and Medline databases up to February 2025. Seven studies met inclusion criteria: four assessed autosomal mCA in both sexes, three evaluated X chromosome (ChrX) mCA in females, and three analyzed Y chromosome (ChrY) mCA in males. Participants had no prior lung cancer diagnoses at baseline. Hazard ratios (HRs) were pooled using inverse variance methods.<br /><br />Results showed that the presence of mCA was significantly associated with increased lung cancer risk overall (HR 1.19, 95% CI 1.08-1.28). This risk was primarily driven by autosomal mCA (HR 1.16, 95% CI 1.02-1.33). In contrast, mCA involving sex chromosomes (ChrX in females and ChrY in males) did not show an association with lung cancer incidence (HR near 1.0 for both). The authors suggest this may be due to fewer oncogenes or tumor suppressor genes related to lung cancer pathology residing on sex chromosomes.<br /><br />In conclusion, the presence of autosomal mosaic chromosomal alterations correlates with a modestly increased risk of developing lung cancer, highlighting mCA detection as a potential biomarker for lung cancer risk stratification. Further research is recommended to validate these findings and explore incorporation of mCA status into lung cancer risk assessment models.

Asset Subtitle

Dhruv Bansal

Meta Tag

Speaker Dhruv Bansal

Topic Pathology and Biomarkers

Keywords

mosaic chromosomal alterations

lung cancer risk

autosomal mCA

sex chromosome mCA

ChrX mCA

ChrY mCA

meta-analysis

cohort studies

biomarker

risk stratification