Ambient Particle Radioactivity and Lung Cancer Survival

Lung cancer persists as a prevalent and deadly disease in the U.S., accounting for 1 in 5 cancer deaths in 2023, with a low survival rate following diagnosis. Ambient particulate matter (PM) is an environmental cause of lung cancer, with limited data suggesting its association with increased risk and poor survival outcomes. Particle radioactivity (PR), a radiometric characteristic of ambient PM, is caused by naturally occurring or anthropogenic radionuclides. Radon decay products can attach to PM2.5 (ambient fine particulate matter less than 2.5 µm in aerodynamic diameter), which, when inhaled, can be deposited into the lungs and potentially contribute to cancer development. Lung cancer, particularly non-small cell lung cancer (NSCLC), is often driven by somatic mutations, which can lead to abnormal cell growth, division, and tumor formation. Oncogenes (such as EGFR and KRAS) and tumor suppressor genes (such as TP53) are frequently involved in somatic mutations, driving the development and progression of NSCLC. While some studies have investigated the effect of ambient PM exposure on lung cancer survival after diagnosis, the impact of environmental exposure to PM2.5 radioactivity and gene-radioactivity (GXR) interactions on lung cancer survival remains unexplored. To address these gaps, this R21 exploratory application will examine the associations between ambient PR exposure and lung cancer survival, utilizing the data from the Boston Lung Cancer Survival (BLCS) cohort, covering from period 2001 through 2018, with over 100,000 person- months of follow-up. In Aim 1, we will assess the effects of pre- and post-diagnosis exposures to PR on the overall survival (OS) and progression free survival (PFS) among the BLCS patients, adjusting for covariates and indoor radon and ambient PM2.5. In addition, by accounting for interactions with key covariates, we aim to identify subgroups with poor survival outcomes. In Aim 2, we will investigate the impact of germline and somatic GXPR interactions on lung cancer survival. This R21 represents a novel and innovative application of established methodologies for assessing radioactive PM exposure and survival analysis to explore a new scientific area, with the potential for significant translational impact in reducing lung cancer mortality. Project Number: 1R21ES037885-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: David Christiani | Institution: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH, BOSTON, MA | Award Amount: $433,185 | Activity Code: R21 | Study Section: Environmental Determinants of Disease Study Section [EDD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11217992