PURPOSE: There are complex and paradoxical patterns in lung cancer incidence by race/ethnicity and gender
compared to non-Hispanic White (NHW) males, non-Hispanic Black (NHB) males smoke fewer cigarettes per day and less frequently but have higher lung cancer rates. Similarly, NHB females are less likely to smoke but have comparable lung cancer rates to NHW females. We use a multistage carcinogenesis model to study the impact of smoking on lung cancer incidence in NHB and NHW individuals in the Multiethnic Cohort Study (MEC). METHODS: The effects of smoking on the rates of lung tumor initiation, promotion, and malignant conversion, and the incidence of lung cancer in NHB versus NHW adults in the MEC were analyzed using the Two-Stage Clonal Expansion (TSCE) model. Maximum likelihood methods were used to estimate model parameters and assess differences by race/ethnicity, gender, and smoking history. RESULTS: Smoking increased promotion and malignant conversion but did not affect tumor initiation. Non-smoking-related initiation, promotion, and malignant conversion and smoking-related promotion and malignant conversion differed by race/ethnicity and gender. Non-smoking-related initiation and malignant conversion were higher in NHB than NHW individuals, whereas promotion was lower in NHB individuals. CONCLUSION: Findings suggest that while smoking plays an important role in lung cancer risk, background risk not dependent on smoking also plays a significant and under-recognized role in explaining race/ethnicity differences. Ultimately, the resulting TSCE model will inform race/ethnicity-specific lung cancer natural history models to assess the impact of preventive interventions on US lung cancer outcomes and disparities by race/ethnicity.