Histological types of lung cancer attributable to fine particulate, smoking, and genetic susceptibility

Abstract

BackgroundFine particulate matter (PM2.5), smoking, and genetic factors are associated with lung cancer. However, the relationship between PM2.5, smoking and subtypes of lung cancer remains unclear. Moreover, it is unclear whether genetic risk modifies the impact of PM2.5 and smoking on incident lung cancer. MethodsA total of 298,069 participants from the UK Biobank study without lung cancer at baseline were included in this study. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated using multivariable Cox proportional models for the association of lung cancer and its subtypes with PM2.5, smoking, and genetic risk. Potential gene-smoking or gene-PM2.5 interactions were also estimated. We further estimated population attributable fractions for incident lung cancer. ResultsDuring 10.4 years of follow-up, 1683 incident lung cancer cases were identified. Our analysis found that genetic variants, smoking, and PM2.5 were significantly associated with incident lung cancer. For different histological types of lung cancer, the HRs for squamous cell lung carcinoma associated with PM2.5 (per 5 μg/m3 increment) and current smoking were 2.76 (95 % CI: 1.72, 4.42, p < 0.001) and 48.64 (95 % CI: 27.96, 84.61, p < 0.001), while the HRs for lung adenocarcinoma were 1.59 (95 % CI: 1.13, 2.23, p < 0.001) and 9.89 (95 % CI: 7.91, 12.36, p < 0.001), respectively. We further found that participants with high levels of PM2.5 pollution and high genetic risk had the highest risk of incident lung cancer (HR = 1.81, 95 % CI: 1.39, 2.35, p < 0.001), while the interaction between PM2.5 and genetic risk was not statistically significant. We observed that the population attributable fractions of lung cancer attributable to current smoking and high PM2.5 exposure were estimated to be 67.45 % and 17.59 %. ConclusionGenetic susceptibility, smoking, and PM2.5 are important risk factors for lung cancer. Both smoking and PM2.5 are more closely associated with an elevated risk of squamous cell lung cancer.