Tobacco Smoking and Risk of Second Primary Lung Cancer.

Abstract

INTRODUCTION\nLung cancer survivors are at high risk of a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined risk factors for SPLC across multiple epidemiologic cohorts and assessed the impact of smoking cessation on reducing SPLC risk.\n\n\nMETHODS\nWe analyzed data from 7,059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, N=3,423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (EPIC, N=4,731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.\n\n\nRESULTS\nOverall, 163 (2.3%) MEC cases developed a SPLC. Smoking pack-years (HR 1.18 per 10 pack-years; P<0.001) and smoking intensity (HR 1.30 per 10 cigarettes per day (CPD); P<0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force s (USPSTF) screening criteria at IPLC diagnosis also had an increased SPLC risk (HR 1.92; P<0.001). Validation studies with PLCO and EPIC showed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (Pmeta<0.001), 1.25 per 10 CPD (Pmeta<0.001), and 1.99 (Pmeta<0.001) for meeting the USPSTF criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR 0.17; P<0.001).\n\n\nCONCLUSIONS\nTobacco smoking is a risk factor for SPLC. Smoking cessation after IPLC diagnosis may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.