A large analysis of the mutational processes of lung cancers in never-smoker patients showed that exposure to fine-particulate air pollution was strongly associated with increased genomic changes, including in cancer-driving and cancer-promoting genetic mutations. Findings from the whole-genome analysis were published in Nature.
Senior and co-corresponding author Maria Teresa Landi, MD, PhD, Senior Investigator and Senior Advisor for Genomic Epidemiology, National Cancer Institute, Bethesda, Maryland, and the other study authors noted that these findings could potentially help lead to more lung cancer prevention strategies for never-smokers.
Study Methods and Rationale
About 25% of all lung cancers are found in never-smokers and are often associated with exposure to second-hand tobacco smoke and air pollution.
The study authors conducted the largest-ever whole-genome analysis of lung cancer among never-smokers based on data from the Sherlock-Lung study, which is a comprehensive study looking to trace the etiology of lung cancer in never-smokers by analyzing genomic tumor and healthy lung tissue data.
Researchers analyzed the cancer genomes of 871 treatment-naive patients with lung cancer who had never smoked. Participants came from 28 geographic locations worldwide.
Key Study Findings
The researchers found that KRAS mutations were 3.8 times more commonly found in adenocarcinomas of never-smokers from North America and Europe than was found in patients from East Asia. Instead, East Asian patients showed a higher prevalence for EGFR and TP53 mutations.
The most single-base substitutions came from signature SBS40a of unknown origin, which was enriched with EGFR mutations.
Signature SBS22a was associated with exposure to aristolochic acid and was observed almost exclusively in patients from Taiwan.
Exposure to secondhand smoke was not associated with individual driver mutations or mutational signatures, but exposure to high levels of air pollution was associated with TP53 mutations and shorter telomeres. These patients also showed an increase in signature SBS4 by 3.9 times and a 76% increase in the clock-like signature SBS5. The findings suggest that secondhand smoke exposure could have a lower overall mutagenicity than air pollution exposure.
A positive dose-response effects was found with air pollution levels, which was correlated with a decrease in telomere length and an increase in somatic mutation frequency attributed mostly to signatures SBS4 and SBS5.
Disclosure: For full disclosures of the study authors, visit nature.com.
