Ethnic differences of genetic risk and smoking in lung cancer: two prospective cohort studies

Background The relative risk of smoking on lung cancer have been reported to be much higher in white population than that in East Asians. However, it’s unknown whether genetic background underlies this disparity between ethnic groups. To assess the role of ethnic differences in genetic factors associated with this phenomenon. Methods We first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and white populations. Then, we compared genetic risk and smoking as well as their interactions on lung cancer between two cohorts, including the China Kadoorie Biobank (CKB) and the UK Biobank (UKB). We also evaluated the absolute risk reduction over a 5-year period. Results 19 SNPs and 23 SNPs were identified to construct the PRSs in Chinese and white populations, and smoking-related loci were only included in white populations. The PRSs were consistently associated with lung cancer risk respectively, but stronger associations were observed in smokers of the UKB (HR 1.26 versus 1.15, P =0.028). A significant interaction between genetic risk and smoking on lung cancer was observed in the UKB (RERI, 11.39 [95% CI, 7.01-17.94]), but not in the CKB. By comparing heavy smokers with nonsmokers, a greater absolute risk reduction was found in the UKB (10.95 versus 7.12 per 1000 person-years, P <0.001), especially for those at high genetic risk. Conclusions In China, tobacco control alone is not enough to reduce the burden of lung cancer, and comprehensive policies should be made to lower its high incidence.