Tobacco Smoking and Risk of Second Primary Lung Cancer

Jacqueline V Aredo; Sophia J Luo; Rebecca M Gardner; Nilotpal Sanyal; Eunji Choi; Thomas P Hickey; Thomas L Riley; Wen-Yi Huang; Allison W Kurian; Ann N Leung; Lynne R Wilkens; Hilary A Robbins; Elio Riboli; Rudolf Kaaks; Anne Tjønneland; Roel C H Vermeulen; Salvatore Panico; Loïc Le Marchand; Christopher I Amos; Rayjean J Hung; Neal D Freedman; Mattias Johansson; Iona Cheng; Heather A Wakelee; Summer S Han

doi:10.1016/j.jtho.2021.02.024

Tobacco Smoking and Risk of Second Primary Lung Cancer

J Thorac Oncol. 2021 Jun;16(6):968-979. doi: 10.1016/j.jtho.2021.02.024. Epub 2021 Mar 17.

Authors

Jacqueline V Aredo¹, Sophia J Luo², Rebecca M Gardner², Nilotpal Sanyal², Eunji Choi², Thomas P Hickey³, Thomas L Riley³, Wen-Yi Huang⁴, Allison W Kurian⁵, Ann N Leung⁶, Lynne R Wilkens⁷, Hilary A Robbins⁸, Elio Riboli⁹, Rudolf Kaaks¹⁰, Anne Tjønneland¹¹, Roel C H Vermeulen¹², Salvatore Panico¹³, Loïc Le Marchand⁷, Christopher I Amos¹⁴, Rayjean J Hung¹⁵, Neal D Freedman⁴, Mattias Johansson⁸, Iona Cheng¹⁶, Heather A Wakelee¹⁷, Summer S Han¹⁸

Affiliations

¹ Stanford University School of Medicine, Stanford, California.
² Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California.
³ Information Management Systems, Rockville, Maryland.
⁴ Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland.
⁵ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California; Department of Medicine, Stanford University School of Medicine, Stanford, California; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California.
⁶ Department of Radiology, Stanford University School of Medicine, Stanford, California.
⁷ Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
⁸ International Agency for Research on Cancer, Lyon, France.
⁹ Epidemiology and Prevention, School of Public Health, Imperial College London, London, United Kingdom.
¹⁰ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Center for Lung Research, Translational Lung Research Center Heidelberg (TLRC-H), Heidelberg, Germany.
¹¹ Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
¹² Division Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
¹³ Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
¹⁴ Department of Medicine, Baylor College of Medicine, Houston, Texas.
¹⁵ Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
¹⁶ Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
¹⁷ Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California.
¹⁸ Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California; Department of Neurosurgery, Stanford University School of Medicine, Stanford, California. Electronic address: summer.han@stanford.edu.

Abstract

Introduction: Lung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk.

Methods: We analyzed data from 7059 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 (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.

Results: Overall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack-years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (p_meta < 0.001), 1.25 per 10 cigarettes per day (p_meta < 0.001), and 1.99 (p_meta < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001).

Conclusions: Tobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.

Keywords: Screening; Second primary lung cancer; Smoking cessation; Surveillance; Tobacco smoking.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Lung
Lung Neoplasms* / epidemiology
Lung Neoplasms* / etiology
Male
Neoplasms, Second Primary* / epidemiology
Neoplasms, Second Primary* / etiology
Prospective Studies
Risk Factors
Tobacco Smoking

Abstract

Publication types

MeSH terms

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