Among persons who have never smoked, women are far more susceptible than men to develop lung cancer when exposed to air pollution, new research shows.

The finding was presented during a press conference here at the 19th World Conference on Lung Cancer (WCLC).

“The global prevalence of tobacco smoking is decreasing overall, but air pollution has become an important risk factor for lung cancer,” said Renell Myers, MD, University of British Columbia, Vancouver, Canada.

Indeed, experts have estimated that 23% of lung cancer deaths worldwide are caused by indoor and outdoor air pollution, she added. In 2013, several expert organizations, including the World Health Organization, listed particulate matter of a concentration of 2.5 ug/m³ (PM_2.5) as an environmental carcinogen.

The study focused on air pollution as an independent risk factor for lung cancer among patients who had never smoked.

It was conducted in 681 lung cancer patients, 35% of whom had never smoked. The remaining 65% either had a history of smoking or were current smokers.

The team carried out a detailed residential history regarding patients’ entire environmental exposure to tobacco smoke wherever they lived from birth until the present.

“We then input these coordinates into a geographic information system which allowed us to extract pollution surface data and compute the overall pollution exposure over their lifetime,” Myers explained. The researchers only tracked exposure to air pollution to 1996, “so we are probably underestimating their actual exposure history,” Myers observed.

Significant Association in Women

“We found a significant association between lung cancer in never-smoking females and air pollution,” Myers reported.

In contrast, no association was seen between exposure to air pollution and lung cancer in never-smoking men, she added.

The researchers noted that levels of air pollution exposure were significantly higher among women who had never smoked compared to women who reported a history of smoking or who were current smokers.

For example, median exposure to air pollution among all cancer patients was 7.1 PM_2.5 ug/m³.

However, among ever-smokers, 6.1% had a PM_2.5 > 10 ug/m³, whereas more than twice that proportion, 15.1%, of never-smokers had exposure levels exceeding PM_2.5 > 10 ug/m³.

Among never-smokers with lung cancer whose level of air pollution exposure was at the highest threshold, almost three quarters were women, and 83% were of Asian descent, the investigators report.

Case Studies

To better characterize differences between men and women with NSCLC and how they might affect OS, Albain and colleagues carried out a prospective study involving 980 patients with stage I to III NSCLC, 186 of whom were women who had never smoked. The other three cohorts consisted of women who had a history of smoking, men who had never smoked, and men who reported a history of smoking.

“Some important and significant differences were noted across the four groups,” Albain reported.

For example, rates of adenocarcinoma were higher in never-smokers than in ever-smokers.

Women were diagnosed with disease of lower stage than men, and more Asians made up the group of never-smokers in both sexes.

Women never-smokers also had more cyclical hormonal exposure, and they used either birth control pills or hormone replacement therapy less, she added.

“And these various factors were also significantly more frequent in never-smokers,” Albain pointed out.

Importantly, more than 90% of never-smokers of both sexes reported a history environmental smoke exposure.

Mutational status also differed by sex and smoking status, Albain continued.

There was a “marked” increase in mutations in epithelial growth factor receptor (EGFR) in both women and men who had never smoked.

In contrast, more KRAS mutations were identified in men and women with a history of smoking.

All of these clinical variables had a major impact on overall survival to 8 years, Albain pointed out

Adjusted for other confounding variables that could influence survival, the data showed that women fared better. Among patients who had never smoked, 64% of women were still alive at 8 years, compared to only 45% of men. Among patients who had ever smoked, 59% of women were still alive at 8 years, compared to 39% of men.

Overall survival also consistently favored women over men, regardless of the stage at which the cancer was diagnosed.

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