估计从不吸烟的个体患肺癌的绝对风险对于肺癌筛查计划非常重要。将环境烟草烟雾 (ETS)（一种已知的肺癌风险因素）数据与捕获整体遗传的多基因风险评分 (PRS) 相结合易感性，以估计台湾从不吸烟者患肺腺癌（LUAD）的绝对风险。这项分析是在台湾肺腺癌遗传流行病学研究（一项病例对照研究）中对从不吸烟的女性中进行的。参与者于2002年9月17日至2011年3月30日期间招募。数据分析于2022年1月17日至7月15日进行。使用25个实现全基因组显着性的遗传变异得出PRS（P < 5 × 10-8 ) 在最近的一项全基因组关联研究中，ETS 被定义为从未暴露、在家中或工作中暴露以及在家中和工作中暴露。使用个体化相干绝对风险估计器软件来估计 LUAD 的终生绝对风险通过使用 PRS 和 ETS 暴露的相对风险估计，以及台湾从不吸烟者的特定年龄肺癌发病率，对对照组中 40 岁不吸烟女性进行了预计 40 年的调查。进行似然比检验以评估 PRS 和 ETS 暴露之间的相加交互作用。数据获得于 1024 名患有 LUAD 的女性（平均 [SD] 年龄为 59.6 [11.4] 岁，47.9% 曾在家中接触过 ETS，19.5% 曾在家中接触过 ETS）曾经在工作中接触过 ETS）和 1024 名对照者（平均 [SD] 年龄，58.9 [11.0] 岁，37.0% 曾经在家中接触过 ETS，14.3% 曾经在工作中接触过 ETS）。在从未接触过 ETS 的女性中，仅使用 PRS 估计的 LUAD 总体平均终生 40 年绝对风险为 2.5%（范围为 0.6%-10.3%）。整合 ETS 和 PRS 数据时，在家或工作中暴露于 ETS 的女性的估计绝对风险为 3.7%（范围为 0.6%-14.5%），暴露于 ETS 的女性为 5.3%（范围为 1.2%-12.1%）在家里和工作中。确定了 ETS 和 PRS 之间的超累加交互作用（交互作用 P = 6.5 × 10-4）。这项研究发现，根据不吸烟女性的 ETS 暴露水平，LUAD 绝对风险的差异归因于遗传易感性。未来的研究有必要将这些发现整合到 LUAD 的扩展风险模型中。

Estimating absolute risk of lung cancer for never-smoking individuals is important to inform lung cancer screening programs.To integrate data on environmental tobacco smoke (ETS), a known lung cancer risk factor, with a polygenic risk score (PRS) that captures overall genetic susceptibility, to estimate the absolute risk of lung adenocarcinoma (LUAD) among never-smokers in Taiwan.The analyses were conducted in never-smoking women in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma, a case-control study. Participants were recruited between September 17, 2002, and March 30, 2011. Data analysis was performed from January 17 to July 15, 2022.A PRS was derived using 25 genetic variants that achieved genome-wide significance (P < 5 × 10-8) in a recent genome-wide association study, and ETS was defined as never exposed, exposed at home or at work, and exposed at home and at work.The Individualized Coherent Absolute Risk Estimator software was used to estimate the lifetime absolute risk of LUAD in never-smoking women aged 40 years over a projected 40-year span among the controls by using the relative risk estimates for the PRS and ETS exposures, as well as age-specific lung cancer incidence rates for never-smokers in Taiwan. Likelihood ratio tests were conducted to assess an additive interaction between the PRS and ETS exposure.Data were obtained on 1024 women with LUAD (mean [SD] age, 59.6 [11.4] years, 47.9% ever exposed to ETS at home, and 19.5% ever exposed to ETS at work) and 1024 controls (mean [SD] age, 58.9 [11.0] years, 37.0% ever exposed to ETS at home, and 14.3% ever exposed to ETS at work). The overall average lifetime 40-year absolute risk of LUAD estimated using PRS alone was 2.5% (range, 0.6%-10.3%) among women never exposed to ETS. When integrating both ETS and PRS data, the estimated absolute risk was 3.7% (range, 0.6%-14.5%) for women exposed to ETS at home or work and 5.3% (range, 1.2%-12.1%) for women exposed to ETS at home and work. A super-additive interaction between ETS and the PRS (P = 6.5 × 10-4 for interaction) was identified.This study found differences in absolute risk of LUAD attributed to genetic susceptibility according to levels of ETS exposure in never-smoking women. Future studies are warranted to integrate these findings in expanded risk models for LUAD.