欧洲人群和东亚人群的吸烟与肺癌相对风险差异之间的遗传背景作用尚不清楚。为评估与吸烟相关的肺癌遗传风险的族群差异所起的作用，我们首先构建了中国和欧洲人群的族群特异性多基因风险评分（PRS），以量化中国和欧洲人群个体的肺癌遗传风险。然后，我们比较了两个队列（包括中国卡多里生物库（CKB）和英国生物库（UKB））中基因风险和吸烟以及它们对肺癌的相互作用。我们还评估了5年期间的绝对风险降低。 中、欧特异性PRS的组成和关联效应存在差异，特别是对于与吸烟相关的位点。PRS与肺癌风险一致关联，但在UKB的吸烟者中观察到更强的关联（风险比（HR）1.26 vs 1.15, P = 0.028）。在UKB中观察到基因风险和吸烟对肺癌的显著相互作用（RERI 11.39（95% CI, 7.01-17.94）），但在CKB中未观察到。CKB的非吸烟者中明显更高的绝对风险，而UKB的重吸烟者与非吸烟者相比具有更大的绝对风险降低（10.95 vs 7.12 per 1000 person-years, P<0.001），尤其是在高遗传风险人群中。 种族差异的遗传因素和东亚非吸烟者肺癌发病率的增加参与了吸烟相关肺癌风险的差异。 © 作者（们）2023；版权所有。由牛津大学出版社代表国际流行病学协会发布。

The role of genetic background underlying the disparity of relative risk of smoking and lung cancer between European populations and East Asians remains unclear.To assess the role of ethnic differences in genetic factors associated with smoking-related risk of lung cancer, we first constructed ethnic-specific polygenic risk scores (PRSs) to quantify individual genetic risk of lung cancer in Chinese and European 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.Differences in compositions and association effects were observed between the Chinese-specific PRSs and European-specific PRSs, especially for smoking-related loci. The PRSs were consistently associated with lung cancer risk, but stronger associations were observed in smokers of the UKB [hazard ratio (HR) 1.26 vs 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. Obvious higher absolute risk was observed in nonsmokers of the CKB, and a greater absolute risk reduction was found in the UKB (10.95 vs 7.12 per 1000 person-years, P <0.001) by comparing heavy smokers with nonsmokers, especially for those at high genetic risk.Ethnic differences in genetic factors and the high incidence of lung cancer in nonsmokers of East Asian ethnicity were involved in the disparity of smoking-related risk of lung cancer.© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.