Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Carcinogenesis. 2021 Jun 21;42(6):874-879. doi: 10.1093/carcin/bgab018.
The US Preventive Services Task Force (USPSTF) recently proposed to widen the current lung cancer screening guideline to include less-heavy smokers. We sought to incorporate both genetic and tobacco smoking data to evaluate the proposed new guideline in white smokers. We constructed a polygenic risk score (PRS) using lung cancer risk variants. Using data from 308 490 participants of European descent in the UK Biobank, a population-based cohort study, we estimated hazard ratios of lung cancer associated with both tobacco smoking and PRS to identify individuals at a similar or higher risk than the group of heavy smokers who are recommended for screening under the USPSTF-2014 guideline (≥30 pack-years, either current or former smokers who quit within 15 years). During a median follow-up of 5.8 years, 1449 incident cases of lung cancer were identified. We found a similar lung cancer risk for current smokers with 20-29 pack-years [hazard ratio = 20.7, 95% confidence interval: 16.3-26.4] and the 'heavy smoker group' defined above (hazard ratio = 19.9, 95% confidence interval: 16.8-23.6) compared with never smokers. Current smokers with 20-29 pack-years did not reach a 6-year absolute risk of 0.0151, a suggested risk threshold for using low-dose computed tomography screening, until the age of 55 years. However, these smokers at high genetic risk (PRS ≥ 80%) reached this risk level at the age of 50. Our findings support the USPSTF proposal to lower the smoking pack-year eligibility to 20 pack-years for current smokers and suggest that PRS for lung cancer could be considered to identify high-risk smokers for screening.
美国预防服务工作组（USPSTF）最近提议扩大当前的肺癌筛查指南，将较少吸烟量的人群纳入其中。我们试图将遗传和吸烟数据结合起来，以评估针对白人吸烟者的新建议。我们使用肺癌风险变异构建了多基因风险评分（PRS）。使用来自 UK Biobank 的 308490 名欧洲血统参与者的基于人群的队列研究数据，我们估计了与吸烟和 PRS 相关的肺癌风险比，以识别与 USPSTF-2014 指南建议的筛查人群（≥30 包年，当前或过去吸烟者，在 15 年内戒烟）风险相似或更高的个体。在中位随访 5.8 年期间，发现了 1449 例肺癌新发病例。我们发现，当前吸烟者中，20-29 包年的肺癌风险与上述“重度吸烟者组”相似[风险比=20.7，95%置信区间：16.3-26.4]。与从不吸烟者相比，当前吸烟者中，20-29 包年的吸烟者在 55 岁之前未达到 0.0151 的 6 年绝对风险，这是建议使用低剂量计算机断层扫描筛查的风险阈值。然而，这些具有高遗传风险（PRS≥80%）的吸烟者在 50 岁时达到了这一风险水平。我们的研究结果支持 USPSTF 将当前吸烟者的吸烟包年资格降低至 20 包年的建议，并表明肺癌 PRS 可用于筛选高危吸烟者。
