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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Friday, April 12, 2024
New insights about probable instigators of lung cancer in those who have never smoked—especially air pollution—have emerged from genomic landscape research into the genetic driver mutations and mutational signatures in a cohort of 871 treatment-naive patients. Marcos Diaz-Gay, PhD, of the University of California San Diego, and colleagues refined the prevalence and intensity of these mutations and signatures from a large sample across various ancestries, geographic locations, and histologies. They presented their work during the American Association of Cancer Research (AACR) Annual Meeting 2024 (Abstract LB231).
The histologies were mostly adenocarcinomas (n = 737) but included carcinoids (n = 61) as well as others infrequently attributed to never-smokers (n = 73). Data on passive smoking were available for 458 patients, with 250 being exposed to secondhand smoke.
The team detected 18 single-base substitution signatures that are “associated with smoking but also observed in lifelong nonsmokers exposed to different environmental mutagens, such as indoor pollution.” Among the 18 signatures, 8—among them, SBS4—were not previously linked to lung cancer in never-smokers.
Of note, although not associated with specific signatures, “secondhand smoke exposure corresponded to increased single-base substitution burden,” continued Dr. Diaz-Gay and co-investigators. “In contrast, we observed a signature-specific association of air pollution with single-base substitution, indel, and doublet-base substitution burden.
Similarly, they found the clock-like signature SBS5 was highly correlated with exposure to air pollution, “potentially acting as a readout of a promotion mechanism where lung cells undergo more cell divisions in individuals living in highly polluted areas.” Across histologies and ancestries, the team observed enrichment of signatures SBS17b and SBS40a as well as KRAS mutations in adenocarcinomas from Europeans, aristolochic acid–associated signature SBS22a and EGFR and TP53 mutations in adenocarcinomas from East Asians, and signature SBS8 and ARID1A mutations in carcinoids from Europeans.
Disclosure: Dr. Diaz-Gay reported no conflicts of interest. For full disclosures of the other study authors, visit abstractsonline.com.
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