Invited Commentary: The Etiology of Lung Cancer in Men Compared With Women

Anthony J. Alberg; Kristin Wallace; Gerard A. Silvestri; Malcolm V. Brock


Am J Epidemiol. 2013;177(7):613-616. 

In This Article

Abstract and Introduction


Lung cancer is the leading cause of cancer death among women in the United States and other Western nations. The predominant cause of lung cancer in women is active cigarette smoking. Secondhand exposure to tobacco smoke is another important cause. The hypothesis that women are more susceptible than men to smoking-induced lung cancer has not been supported by the preponderance of current data, as noted by De Matteis et al. (Am J Epidemiol. 2013;177(7):601–612) in the accompanying article. However, aspects of lung cancer in men and women continue to indicate potential male-female differences in the etiology of lung cancer, based on several observations: 1) among never smokers, women have higher lung cancer incidence rates than men; 2) there is evidence that estrogen may contribute to lung cancer risk and progression; and 3) there are different clinical characteristics of lung cancer in women compared with men, such as the higher percentage of adenocarcinomas in never smokers, the greater prevalence of epidermal growth factor receptor gene (EGFR) mutations in adenocarcinomas among never smokers, and better prognosis. Considered in total, observations such as these offer enticing clues that, even amid cigarette smoking and other commonalities in the etiology of lung cancer in men and women, distinct differences may remain to be delineated that could potentially be of scientific and clinical relevance.


Before becoming the most common cause of cancer death worldwide, lung cancer was a rare disease in the early 1900s. The fact that lung cancer was once so rare in both sexes attests to the fact that almost the entire present lung cancer burden is caused by environmental exposures. Tremendous progress has been made in characterizing the environmental causes of lung cancer, with a single etiological agent—cigarette smoking—being the predominant cause, accounting for approximately 80%–90% of lung cancer cases in countries where cigarette smoking is common.[1] In both sexes, extensive bodies of evidence have consistently demonstrated extremely strong associations between smoking and lung cancer that follow clear dose-response gradients according to the number of years smoked, the number of cigarettes smoked per day, and ages at starting and stopping smoking.[2] Compared with persistent smoking, the risk of lung cancer is reduced following smoking cessation.[2]

Cigarette smoking is such a potent cause of lung cancer in both sexes that it can be tracked on a population-wide scale, since spatial and temporal trends in lung cancer occurrence closely mirror trends in smoking prevalence, with rates of occurrence lagging behind smoking rates by about 20 years.[3] In the United States, because of historical trends in cigarette smoking prevalence, which peaked approximately 2 decades earlier in men than in women, the epidemic of lung cancer started later in women than in men. Whereas lung cancer incidence rates in men have been declining for the past 2 decades, a significant downturn in lung cancer incidence rates among women was only recently observed in 2003–2007 data.[4] Far more men than women still die from lung cancer each year, but the gender gap in lung cancer mortality is steadily narrowing. Thus, from a public health perspective, the message is clear: Effective tobacco control interventions are the central strategy for preventing lung cancer in both men and women.

As the major associations between smoking and lung cancer were characterized, more refined questions were addressed. As De Matteis et al.[5] illustrate in this issue of the Journal, an example is the keen interest in the hypothesis that women may be more susceptible to smoking-induced lung cancer than men.