Long-term air pollution and lung cancer incidence by histological subtypes

Background: There is mounting evidence of long-term exposure to air pollution and incidence of lung cancer based on large cohort studies worldwide. A few subsequent studies have suggested that the association may vary by histological subtypes, although findings have been inconsistent. This study aimed to investigate whether air pollution affects a specific histological subtype of lung cancer more than the others using a population-representative cohort including 2 million adults. Methods: Our study population includes 2,346,332 adults who were aged 30 years or over in 2007, participated in health examinations for 2005-2007, and were retrospectively followed-up until 2020 in the National Health Insurance Services database linked with the Korea Central Cancer Registry of South Korea. We identified lung cancer incidence of three histological subtypes, including adenocarcinoma (AD), squamous cell carcinoma (SqCC), and small cell carcinoma (SCC), based on the International Classification Diseases for Oncology. Individual-level long-term exposures to particulate matter ≤ 2.5 µg/m 3 in diameter (PM 2.5 ) and nitrogen dioxide (NO 2 ) were 5-year average concentrations estimated at district-level home addresses by previously-validated exposure prediction models. Then, we applied time-varying Cox proportional hazard model to estimate hazard ratios of lung cancer incidence for 10 µg/m 3 and 10 ppb increases in PM 2.5 and NO 2 respectively. Results: For 20,811 new lung cancer cases occurred over 13 years, AD, SqCC, and SCC made up 52, 21, and 10 %, respectively. We found no association of total lung cancer incidence for both pollutants (PM 2.5 : HR=1.065, 95% CI=0.957-1.186; NO 2 : 0.980, 0.957-1.004). However, PM 2.5 was associated with SqCC (1.353, 1.054 -1.738), but not associated with AD (0.892, 0.722-1.038) and SCC (1.148,0.818-1.609). In contrast, NO 2 showed the association for AD (1.064, 1.027-1.102) but not for SqCC 0.905 (0.861 - 0.951) and SSC 0.956 (0.888 - 1.029). Discussion: Our findings of different associations by pollutants and histological subtypes suggest different mechanistic roles in lung cancer development depending on the pollutant.