Air Pollution 'Strongly Associated' With DNA Mutations Tied to Lung Cancer - Health Wellness Line

 Air pollution may be a sneaky factor in the rising number of nonsmoker lung cancer cases around the world. A genome study has now found that outdoor smog and soot are strongly associated with DNA mutations related to lung cancer – including known drivers seen in smokers, and new ones unique to non-smokers.

 The more pollution someone was exposed to, the more mutations scientists found in their lung tumors.

 The findings don't mean that air pollution is directly causing lung cancer, but they do contribute to evidence suggesting that possibility.

 "We're seeing this problematic trend that never-smokers are increasingly getting lung cancer, but we haven't understood why," explains biomolecular scientist Ludmil Alexandrov from the University of California San Diego (UCSD).

 "Our research demonstrates that the same kinds of DNA mutations that are typically linked to smoking are strongly associated with air pollution." The extensive international analysis examined the cancer genomes of 871 individuals from four continents, all of whom had lung cancer despite never having smoked and who had not yet received cancer treatment.

 Those who lived in regions with high levels of air pollution were significantly more likely to have TP53 mutations, EGFR mutations, and shorter telomeres.

 Lung cancers are characterized by abnormalities in the TP53 and EGFR genes, particularly those caused by the SBS4 DNA mutation, and shorter telomeres are linked to faster aging. In the current study, non-smokers who lived in areas with higher air pollution were nearly four times more likely to exhibit SBS4 signatures as those who lived in regions with cleaner air.

 By contrast, exposure to secondhand smoke, which is a known cancer risk, showed only a slight increase in genetic mutations.

 "If there is a mutagenic effect of secondhand smoke, it may be too weak for our current tools to detect," says geneticist Tongwu Zhang from the US National Cancer Institute (NCI).

 Not so for air pollution or tobacco smoking: both were strongly linked to DNA mutations.

 About 10 to 20% of lung cancer cases in the United States today are caused by people who have never smoked or who have smoked fewer than 100 cigarettes in their lives. Scientists have long suspected that air pollution could be a contributing factor, but exactly how fine particulate matter in the air compares to tobacco smoking or secondhand smoke exposure remains unclear.

 Although the majority of these conclusions are based on observational analyses, some studies suggest that breathing polluted air is comparable to smoking a pack per day. The current study digs further by looking at some of the molecular mechanisms that may be at play.  It compared the lung cancer genomes of the 871 non-smokers with tumors from 345 smokers, to find similarities and differences.

 The majority of non-smokers with lung cancer had adenocarcinomas (the most common type of lung cancer), and nearly 5 percent of those tumors showed the SBS4 mutational signature.

 Additionally, a novel signature known as SBS40a, which was absent in tobacco smokers, was seen in 28% of nonsmokers. Strangely, the cause of this particular mutational driver was unknown, but doesn't seem to be environmental in nature.

 "We see it in a majority of cases in this study, but we don't yet know what's driving it," says Alexandrov.  "This is something completely different, and it opens up a completely new area for research." Since the current study only looked at air pollution levels in the area, it can't say how much each person was directly exposed to fine airborne particles. Participants who said they had never smoked may have also smoked more than reported.

 These limitations notwithstanding, the overall findings align with other evidence indicating that soot or smog may trigger tumor growth in a similar way to cigarette chemicals.

 According to epidemiologist Maria Teresa Landi of the National Cancer Institute, "This is an urgent and growing global problem that we are working to understand regarding never-smokers." The team now hopes to include cancer genomes from a more diverse global cohort in their research.