My good friend Heather Wakelee, along with her colleagues at Stanford, just published an important study in the Journal of Clinical Oncology on the incidence of lung cancer among never-smokers, essentially the first and most comprehensive work defining the magnitude of the problem. I've mentioned that never-smokers with lung cancer are a particular interest of mine, and that this population is emerging as a distinct subpopulation with different characteristics and response to therapies, especially EGFR-based therapies. Dr. Wakelee's paper describes several issues about never-smokers with lung cancer on a much larger scale.

The study reviewed the incidence of lung cancer cases among both men and women in six different large cohort studies from various countries and ethnic groups over the last few decades (more concentrated on recent years). Incidence is the number of new cases of a disease (expressed in cases per year, for instance), as opposed to prevalence, which is the number of cases in the population at a given time (such as an estimate that there are 25,000 never-smokers with lung cancer in the US right now, for example). And a cohort study is an evaluation of a group of people, such as the Nurses Health Study, which closely followed the habits and health of over 120,000 women from 1976 to 2002. Dr. Wakelee's paper reviewed the incidence of lung cancer among never-smokers in 6 different cohort studies that included nearly 1.4 million people and over 4,000 new lung cancers diagnosed in those groups over time.

They documented that the incidence of lung cancer among never-smoking women is markedly higher in women than men (about double), but it is still 12-30 times higher in smokers than in never-smokers of either sex. There also appears to be a potential role for genetic and/or other environmental exposures, such as passive (second-hand) smoking, since one of the included studies from Sweden showed lower rates of lung cancer than US populations for either sex, and comparing smokers to smokers and never-smokers to never-smokers. Although no Asian trials were included, I suspect they would show very interesting differences compared to US or European trials, since so many of the Asian studies have 30-50% of their patients as reported never-smokers. Whether those differences are due to genetics, environmental exposures like second-hand smoke, or some combination of these factors is just not known.

There were no obvious differences in the age of never-smokers diagnosed with lung cancer vs. smokers with lung cancer. As expected, the majority of never-smokers had adenocarcinomas, but the range was only 53-67% adenocarcinomas, which is less than I would have expected. Still, that's the value of new data coming in. Live and learn.

Dr. Wakelee and her colleagues point out that their report can't speak to the general observation among many lung cancer specialists that the proportion of never-smokers is rising over time. There is some suggestive evidence of this in a few relatively small snapshots comparing the proportion of never-smoker lung cancer cases from 20+ years ago to more recent time points, but the study from Stanford really does more to establish a clear benchmark of the situation as we know it now. It represents an important milestone in building momentum in the study of never-smokers with lung cancer.

Some other interesting work in never-smokers with lung cancer is just emerging, so I'll continue with more on the biology and other characteristics very soon.