Rationale: The individual effects of early-life tobacco smoke exposure and its interactions with genetic factors on lung cancer in adulthood remain unclear. Objectives: To investigate the associations of early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) with lung cancer incidence and mortality. Methods: A total of 432,831 participants from the UK Biobank study were included. We estimated the associations of in utero exposure to tobacco smoke, the age of smoking initiation and their interactions with PRSs with lung cancer incidence and mortality in adulthood using Cox proportional hazard models. Measurements and Main Results: Lung cancer incidence (hazard ratio [HR]: 1.59, 95% confidence interval [CI], 1.44-1.76) increased among participants with in utero tobacco exposure. Multivariable-adjusted HRs (with 95% CIs) of lung cancer incidence for smoking initiation in adulthood, adolescence, and childhood (versus never-smokers) were 6.10 (5.25-7.09), 9.56 (8.31-11.00), and 15.15 (12.90-17.79) (Ptrend < 0.001). Similar findings were observed in lung cancer mortality. Participants with high PRSs and in utero tobacco exposure (versus low PRSs participants without in utero exposure) had an HR of 2.35 for lung cancer incidence (95% CI, 1.97-2.80, Pinteraction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction = 0.032). High PRSs with smoking initiation in childhood (versus never-smokers with low PRSs) had HRs of 18.71 for incidence (95% CI, 14.21-24.63, Pinteraction = 0.004) and 19.74 for mortality (95% CI, 14.98-26.01, Pinteraction = 0.033). Conclusions: In utero and childhood/adolescence exposure to tobacco smoke and its interaction with genetic factors may substantially increase the risks of lung cancer incidence and mortality in adulthood.

中文翻译：

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在子宫内和童年/青春期接触烟草烟雾、遗传风险以及成年期肺癌发病率和死亡率。

理由：生命早期烟草烟雾暴露的个体影响及其与成年期肺癌遗传因素的相互作用仍不清楚。目的：调查生命早期烟草暴露及其与多基因风险评分 (PRS) 的相互作用与肺癌发病率和死亡率之间的关系。方法：共有来自英国生物样本库研究的 432,831 名参与者被纳入。我们使用 Cox 比例风险模型估计了子宫内烟草烟雾暴露、开始吸烟的年龄及其与 PRS 的相互作用与成年期肺癌发病率和死亡率之间的关联。测量和主要结果：在子宫内接触烟草的参与者中，肺癌发病率（风险比 [HR]：1.59，95% 置信区间 [CI]，1.44-1.76）增加。成年期、青春期和儿童期（相对于从不吸烟者）开始吸烟的肺癌发病率的多变量调整 HR（95% 可信区间）分别为 6.10 (5.25-7.09)、9.56 (8.31-11.00) 和 15.15 (12.90- 17.79)（趋势 < 0.001）。在肺癌死亡率中观察到类似的发现。具有高 PRS 和子宫内烟草暴露的参与者（相对于没有在子宫内暴露的低 PRS 参与者）肺癌发病率的 HR 为 2.35（95% CI，1.97-2.80，Pinteraction = 0.089），死亡率为 2.43（95% CI， 2.05-2.88，Pinteraction = 0.032）。童年开始吸烟的高 PRS（相对于 PRS 低的从不吸烟者）的发病率 HR 为 18.71（95% CI，14.21-24.63，Pinteraction = 0.004），死亡率为 19.74（95% CI，14.98-26.01，Pinteraction = 0.033）。结论：