Incorporating both genetic and tobacco smoking data to identify high-risk smokers for lung cancer screening.

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.