Mosaic Chromosomal Alterations and Risk of Lung Cancer

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In a study reported in The Lancet Oncology, Qin et al found that the presence of mosaic chromosomal alterations detected in blood-derived DNA was associated with an increased risk of lung cancer among persons of Chinese and European heritage.

Study Details

The study involved two cohorts: individuals from the Nanjing Lung Cancer Cohort (NJLCC) case-control study, consisting of 10,248 individuals with and 9,298 individuals without lung cancer; and individuals from the prospective cohort UK Biobank (UKB) study, consisting of 2,088 with and 448,733 without lung cancer. 

Key Findings

Mosaic chromosomal alterations were found in 4.08% of individuals with vs 3.54% of those without lung cancer in the NJLCC cohort (mosaic losses in 1.75% vs 1.05%) and in 5.60% vs 3.56% in the UKB cohort (mosaic losses in 1.10% vs 0.62%).

The presence of mosaic chromosomal alterations was associated with significantly increased risk of lung cancer in both the NJLCC cohort (odds ratio [OR] = 1.19, P = 9.32 × 10-³) and the UKB cohort (hazard ratio [HR] = 1.24, P = 8.71 × 10-³). Mosaic type–specific analysis showed that the increased risk was mainly driven by the presence of mosaic copy loss in both the NJLCC cohort (OR = 1.81, P = 6.69 × 10-⁷) and UKB cohort (HR = 1.40, P = .048). Analysis in the NJLCC cohort showed increased risk among individuals with expanded cell fractions of mosaic chromosomal alterations (ie, ≥ 10% vs < 10%), with odds ratios of 1.61 (95% confidence interval [CI] = 1.26–2.08) vs 1.03 (95% CI = 0.83–1.26; P = 6.41 × 10-³ for heterogeneity).

A significant interaction was observed between polygenic risk score and mosaic losses in risk of lung cancer in both the NJLCC cohort (P = .030 for interaction) and UKB cohort (P = .043). Compared with individuals without mosaic losses and low genetic risk, those with expanded mosaic losses (cell fractions ≥ 10%) and high genetic risk had a significantly greater risk of lung cancer in the NJLCC cohort (OR = 6.40, 95% CI = 3.22–12.69) and UKB cohort (HR = 3.75, 95% CI = 1.86–7.55). The interaction of polygenic risk score and mosaic losses was associated with relative excess risks of lung cancer of 3.67 (95% CI = 0.49–6.85) in the NJLCC cohort and 2.15 (95% CI = 0.12–4.19) in the UKB cohort.  

The investigators concluded, “Mosaic chromosomal alterations act as a new endogenous indicator for the risk of lung cancer and might be jointly used with [polygenic risk score] to optimize personalized risk stratification for lung cancer.”

Hongbing Shen, PhD, and Zhibin Hu, PhD, of Nanjing Medical University, are the corresponding authors for The Lancet Oncology article.

Disclosure: The study was funded by the National Natural Science Foundation of China, Outstanding Youth Foundation of Jiangsu Province, and others. For full disclosures of the study authors, visit

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