Preventing Lung Cancer in People Who Have Never Smoked

Issue 28, Winter/Spring 2016

While there is general knowledge that tobacco smoking is a powerful cause of lung cancer, indeed the cause of most cases in the United States and worldwide, lung cancer does occur in never smokers. Cases of lung cancer were documented before the cigarette smoking epidemic took hold in the early 20th century; lung cancer occurs in populations where there is no or very  little smoking; and workers who do not smoke develop lung cancer because of cancer-causing workplace contaminants.

There are also other ubiquitous causes of lung cancer aside from smoking, including radon indoors and air pollution outdoors and indoors, particularly from burning of biomass fuels in low-income countries. However, our understanding of lung cancer in never smokers is incomplete, reflecting the relatively small numbers of such cases and the resulting limitation to research.

How important is lung cancer in never smokers? The death rate for lung cancer in never smokers is around 10 per 100,000 per year, about 5 % of the rate in smokers of a pack of cigarettes per day.  This year there will be about 20,000 cases in the United States, producing around 15,000 lung cancer deaths out of a total of more than 158,000 lung cancer deaths per year.

For comparison, mortality from breast cancer will be about 41,000 and from prostate cancer about 26,000. In fact, lung cancer in never smokers ranks as the seventh leading cause of cancer death in the United States.

Global estimates are highly uncertain; there are an estimated 1.8 million lung cancer cases worldwide and if 10-15% are in never smokers the count ranges from about 180,000 to 270,000 in people who never smoked.

There is also uncertainty about whether the rate at which lung cancer occurs in never smokers has increased in recent decades, potentially reflecting changes in the environmental factors that cause lung cancer.

To answer that question, researchers put together data from 13 large studies from around the world and also examined the records of cancer registries.  Over a timespan that reached back to the 1930s, they did not find any indication that lung cancer in never smokers was becoming more common.

They did find that the rates of new cases were similar in men and women and that rates were highest in Asian men and women. One hypothesis is that never-smoking Asian women have a high lung cancer frequency because of exposure to cooking fumes, particularly from high-temperature cooking in woks.

What are the causes of lung cancer in never smokers? The list includes three environmental agents: radon indoors, outdoor and indoor air pollution, and secondhand smoke or SHS—the mixture of sidestream smoke from the smoldering cigarette and the exhaled mainstream smoke.

There are also agents that workers are exposed to, including radon in underground mines, asbestos, silica dust, beryllium, arsenic, formaldehyde, and benzo-a-pyrene. Most of the occupational causes were identified through epidemiological studies of workers who had exposures far higher than those that would generally be found today in regulated workplaces. Nonetheless, occupational lung cancer remains a problem worldwide, particularly in some countries where workplace exposures are not yet sufficiently controlled.

A past history of tuberculosis is also associated with increased risk, perhaps because of the scarring of the lung.  Genes that might increase risk have been sought for both smokers and never smokers. The search has proved challenging, particularly in never smokers, but there are promising leads under investigation.

From a clinical perspective, lung cancer in never smokers varies in important ways in comparison to cancers in smokers. The spectrum of mutations in the DNA differs between the two groups. There are potential therapeutic implications, particularly in regard to the high incidence of mutations of the gene encoding the epidermal growth factor receptor in never smokers.

Also, overall survival tends to be better in never smokers than in smokers with lung cancer.

While the understanding of lung cancer in never smokers is incomplete, there are effective ways to reduce its occurrence. First, exposure to secondhand smoke has dropped greatly over the last three decades and can be pushed lower; second, exposure to radon can be reduced by following the recommendation of the US Environmental Protection Agency to measure indoor radon concentration and to take steps to control radon if the concentration exceeds guidelines; third, improvements in outdoor air quality in the United States should reduce lung cancer burden; and fourth, the burden of occupational cancer should continue to fall in the United States, reflecting the impact of regulations implemented decades ago and subsequently tightened for some agents.  

Jonathan M. Samet, MD, MS

Jonathan M. Samet, MD, MS
Distinguished Professor and Flora L. Thornton Chair
Department of Preventive Medicine
Keck School of Medicine of USC
Director, USC Institute for Global Health
University of Southern California
Los Angeles, CA

References

  1. Rudin CM, Avila-Tang E, Harris CC, Herman JG, Hirsch FR, Pao W, et al. Lung cancer in never smokers: molecular profiles and therapeutic implications. Clin Cancer Res 2009;15(18):5646-61 doi 10.1158/1078-0432.ccr-09-0377.
  2. Samet JM, Avila-Tang E, Boffetta P, Hannan LM, Olivo-Marston S, Thun MJ, et al. Lung cancer in never smokers: clinical epidemiology and environmental risk factors. Clin Cancer Res 2009;15(18):5626-45 doi 10.1158/1078-0432.ccr-09-0376.
  3. Thun MJ, Hannan LM, Adams-Campbell LL, Boffetta P, Buring JE, Feskanich D, et al. Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies. PLoS medicine 2008;5(9):e185 doi 10.1371/journal.pmed.0050185.