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.
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.
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 thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.