ASCO 2024: Air Pollution, Gene-Environment Interactions, and Risk of NSCLC in Nonsmokers

By: Joshua D. Madera, MD
Posted: Wednesday, June 19, 2024

Efforts to identify the underlying mechanism of clonal hematopoiesis of indeterminate potential (CHIP) in the development of non–small cell lung cancer (NSCLC) have revealed a significant interaction between CHIP and small particulate air matter pollution (PM_2.5) exposure, according to a study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 10514). PM_2.5 levels impact the relationship between CHIP and NSCLC by potentially increasing systemic inflammation and the lung microenvironment, thus increasing the risk of NSCLC in nonsmokers, explained Michael J. Rauh, MD, PhD, of Queen’s University, Kingston, Ontario, Canada, and colleagues.

Data from a total of 451,095 patients were collected from the United Kingdom Biobank. Peripheral blood samples were obtained from patients for whole-exome sequencing to identify the patients’ CHIP status. Patients with evidence of a somatic driver mutation at a variant allele frequency greater than 2% were defined as having a positive CHIP status. In addition, the United Kingdom cancer registry was employed to determine the number of cases of NSCLC, and the ambient regional measures from 2010 were used to determine PM_2.5 exposure.

The study authors identified the presence of CHIP in 15,633 patients. A diagnosis of NSCLC was found in 1,983 patients, with 307 of these diagnoses occurring in individuals who never smoked. After the investigators adjusted for smoking status, an association was revealed between NSCLC and CHIP status (hazard ratio [HR] = 1.73). Similarly, in nonsmokers alone, an association was identified between NSCLC and CHIP status (HR = 2.01). No significant interactions were identified between PM_2.5 levels and NSCLC (HR = 1.00). However, a significant association between PM_2.5 levels and CHIP status was found (HR = 1.46). Furthermore, the interaction between CHIP status and PM_2.5 was significantly associated with an increase in the inflammatory markers interleukin-6 and C-reactive peptide.

Disclosure: Dr. Rauh reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.

2024 ASCO Annual Meeting

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