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Lung Cancer Incidence in Never Smokers

Heather A. Wakelee, Ellen T. Chang, Scarlett L. Gomez, Theresa H. Keegan, Diane Feskanich, Christina A. Clarke, Lars Holmberg, Lee C. Yong, Laurence N. Kolonel, Michael K. Gould, Dee W. West

From the Division of Oncology, Department of Medicine and the Department of Health Research and Policy, Stanford University School of Medicine, Stanford; Northern California Cancer Center, Fremont; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital; Harvard Medical School, Boston, MA; Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH; Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI; and Regional Oncologic Center, Uppsala University Hospital, Uppsala, Sweden

Address reprint requests to Heather Wakelee, MD, Division of Medical Oncology, Stanford Clinical Cancer Center, 875 Blake Wilbur Dr, Stanford, CA 94305-5826; e-mail: hwakelee{at}stanford.edu

Purpose: Lung cancer is a leading cause of cancer death worldwide. Although smoking remains the predominant cause of lung cancer, lung cancer in never smokers is an increasingly prominent public health issue. However, data on this topic, particularly lung cancer incidence rates in never smokers, are limited.

Methods: We reviewed the existing literature on lung cancer incidence and mortality rates among never smokers and present new data regarding rates in never smokers from the following large, prospective cohorts: Nurses’ Health Study; Health Professionals Follow-Up Study; California Teachers Study; Multiethnic Cohort Study; Swedish Lung Cancer Register in the Uppsala/Örebro region; and First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study.

Results: Truncated age-adjusted incidence rates of lung cancer among never smokers age 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non–smoking-associated lung cancer. The distinct biology of lung cancer in never smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never smokers.

Conclusion: Lung cancer in never smokers is an important public health issue, and further exploration of its incidence patterns, etiology, and biology is needed.

Supported in part by Grant No. R01 CA77398 from the National Cancer Institute and Contract No. 97-10500 from the California Cancer Research Fund.

The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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