Impact of Environmental Exposures on Lung Cancer in Patients Who Never Smoked

Background: Despite the rising incidence of lung cancer in patients who never smoked, environmental risk factors such as ambient air pollution in this group are poorly described. Our objective was to identify the relationship of environmental exposures with lung cancer in patients who never smoked.

Methods: A prospectively collected database was reviewed for all patients with non-small cell lung carcinoma (NSCLC) who underwent resection from 2006 to 2021. Environmental exposures were estimated using the geocoded home address of patients. Logistic regression was used to determine the association of clinical and environmental variables with smoking status. Kaplan-Meier and Cox proportional hazards analyses were used to assess survival.

Results: A total of 665 patients underwent resection for NSCLC, of which 67 (10.1%) were patients who never smoked and 598 (89.9%) were current/former smokers. Patients who never smoked were more likely of white race (p = 0.001) and had well-differentiated tumors with carcinoid or adenocarcinoma histology (p < 0.001). Environmental exposures were similar between groups, but patients who never smoked had less community material deprivation (p = 0.002) measured by household income, education, health insurance, and vacancies. They had improved overall survival (p = 0.012) but equivalent cancer recurrence (p = 0.818) as those who smoked. In univariable Cox analyses, fine particulate matter (HR: 1.447 [95% CI 1.197-1.750], p < 0.001), distance to nearest major roadway (HR: 1.067 [1.024-1.111], p = 0.002), and greenspace (HR: 0.253 [0.087-0.737], p = 0.012) were associated with overall survival in patients who never smoked.

Conclusions: Lung cancer patients who never smoked have unique clinical and pathologic characteristics, including higher socioeconomic status. Interventions to reduce environmental exposures may improve lung cancer survival in this population.