Air Pollution Increases Lung Cancer Risk in Nonsmokers

Pam Harrison

September 25, 2018

TORONTO — 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 (PM2.5) 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 PM2.5 ug/m3.

However, among ever-smokers, 6.1% had a PM2.5 > 10 ug/m3, whereas more than twice that proportion, 15.1%, of never-smokers had exposure levels exceeding PM2.5 > 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.

"Using a logistic regression model, we demonstrated a significant association between air pollution exposure and never-smokers compared to ever-smokers in women (P < .001)," the researchers conclude.

Asked by Medscape Medical News how air pollution levels could be so high in Vancouver, a city renowned for its pristine air, Myers noted that the majority of the lung cancer patients who presented to their cancer agency and who were enrolled in the study were foreign born.

Approximately 75% of patients who were never-smokers were foreign born, compared to only about 45% of those who reported a history of smoking.

"We don't have causality data, but this study gives us information to see if we can go further and look at the general population and eventually develop a risk prediction model so we could screen segments of the population who are at high risk for lung cancer, because currently, no one is screening low-risk nonsmokers for lung cancer," she emphasized.

Case-Series Study

In an unrelated case-series study, Kathy Albain, MD, professor of medicine, Loyola University Chicago, in Illinois, told the press briefing that many different reports have noted differences between men and women with non–small cell lung cancer (NSCLC), including differences in environmental exposures, sex hormone influences, and rates of overall survival (OS).

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.

Table. 8-Year Adjusted Overall Survival by Stage of NSCLC

  Women Men
Stage I 71% 55%
Stage II 53% 33%
Stage III 28% 11%


"When you come down to it and adjust for everything that influences survival, there is still a distinct difference in overall survival, with females doing significantly better than males," Albain told Medscape Medical News.

"What we need to do now is move to the next level and ask why," she added.

Asked by Medscape Medical News whether physicians are aware that women who have never smoked are still at risk for lung cancer, press conference moderator Andrea Bezjak, MD, University of Toronto, felt that at least some physicians probably do not realize this to be the case.

"We find that lung cancer is the last thing on the family doctor's mind when even smokers or exsmokers come to them with a cough," Bezjak said.

She added that often, the cause of the cough is bronchitis, pneumonia, or asthma — "there are many reasons for a cough," she suggested.

"And, of course, the female nonsmokers look healthy — they don't look like the picture of lung cancer," Bezjak said.

Bezjak suggested that, in this regard, advocacy groups can help, because they try to make everyone aware that lung cancer can happen to healthy, vibrant people who have done everything "right," not just smokers.

Roughly two thirds of patients diagnosed with lung cancer have either never smoked or did smoke but then quit, she commented.

"One day, we will probably have a blood test or a breath test that will be easy to use in order to diagnose lung cancer, but right now, it's a challenge," Bezjak admitted.

Dr Myers and Dr Bezjak have disclosed no relevant financial relationships. Dr Albain has served on an advisory board for Genentech and Genomic Health.

19th Annual World Conference on Lung Cancer (WCLC). Abstract 144865 and 14526, presented September 24, 2018.


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