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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Thursday, April 18, 2024
Estrogen metabolites may contribute to the development of lung cancer among people who have never smoked, according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract 1467/5). Citing a consistent rise in the incidence of non–small cell lung cancer (NSCLC) among individuals who have never smoked and the preponderance of females within that population, Mitchell Cheung, PhD, of Fox Chase Cancer Center, Philadelphia, and colleagues set out to explore the potential contribution of estrogen to lung tumorigenesis. In their findings, the investigators reported that estrogen is metabolized extensively in both mouse and human lungs, resulting in the generation of derivatives that seem to contribute to the development of lung cancer among people who have never smoked.
“We have developed a noninvasive assay to measure various estrogen metabolites and have already discovered that NSCLC patients with tumors harboring mutant EGFR produce more carcinogenic estrogen than healthy control subjects,” said senior author of the study, Margie Clapper, PhD, in a Fox Chase press release. “Our results suggest that modulation of estrogen metabolism may be a promising strategy for the early interception of NSCLC.”
The researchers observed that prolonged exposure of noncancerous human bronchial epithelial cells to estrogen for prolonged periods led to the accumulation of double-strand DNA breaks and transformation, with cells acquiring characteristics of tumor cells. They then employed The Cancer Genome Atlas database to determine the relevance of their findings to lung tissue from patients with NSCLC.
“We performed a comprehensive analysis to see if we could determine the mechanisms underlying that transformation process. The plan is to target these pathways for early interception of lung cancer in the future,” said Dr. Cheung. “Most exciting was the discovery that the genes dysregulated by estrogen metabolites were not only altered in tumors from NSCLC patients, but more importantly, associated with a worse prognosis.”
Disclosure: The study authors reported no conflicts of interest.
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