Ghosts in the Genome: Why Taiwan’s Never-Smokers Are Getting Lung Cancer

Ghosts in the Genome: Why Taiwan’s Never-Smokers Are Getting Lung Cancer


For years, doctrs in Taiwan have been puzzled by a recurring question: why are people who have never smoked developing lung cancer?

A major international study published this week in Nature may finally offer an answer. By sequencing the complete genomes of lung tumours from never-smokers around the world, researchers have identified a rare genetic fingerprint linked to a once-common toxin—and it’s showing up almost exclusively in Taiwan.

The mutation signature, known as SBS22a, is strongly associated with aristolochic acid, a natural compound found in some traditional herbal remedies. The acid has long been known to cause kidney failure and urinary tract cancers, and was banned in Taiwan in 2003. But now, for the first time, it has been linked to lung cancer.

Of the 871 never-smoking lung cancer patients included in the global study—spanning 28 countries—nearly 90 per cent of those with SBS22a mutations were from Taiwan. The discovery suggests that aristolochic acid exposure may continue to affect people long after it was officially removed from the market.

“This is a stark reminder that our genomes carry a memory of past environmental exposures,” says Dr. Yung-Chi Cheng, a cancer researcher not affiliated with the study. “Even if a carcinogen is banned, the biological damage can emerge decades later.”

Mutational Echoes of a Banned Substance

Aristolochic acid was once found in a variety of traditional medicines, including plants such as Guān Mù Tōng and Guǎng Fáng Jǐ. Its use was widespread in East Asia before growing evidence of its toxicity led to regulatory bans. Taiwan prohibited all related products in 2003.

However, the new findings suggest the story may not have ended there. Researchers say illicit use, black-market availability, or imported supplements may still be exposing people to the compound. Alternatively, the mutations may be the long-term result of exposures from decades past.

“The geographic concentration of this mutation in Taiwan is not a coincidence,” says lead author Jun Li at the Wellcome Sanger Institute. “It tells us that something specific to the environment or practices in that region left a mark in the genome.”

Air Pollution: Another Genetic Assault

The study also implicates air pollution—specifically fine particulate matter (PM2.5)—as a key contributor to genetic mutations in lung cancer among non-smokers. The researchers found that when annual PM2.5 levels exceeded 20 micrograms per cubic metre, the overall mutation burden in lung cells increased sharply.

Notably, this included changes to TP53, a tumour suppressor gene commonly associated with aggressive cancer, as well as significant telomere shortening—a marker of cellular aging and damage.

“In some cases, the impact of air pollution on the genome was even greater than second-hand smoke,” says Li.

This could help explain why lung cancer is increasingly common among urban residents in Asia, particularly women, who often have low tobacco exposure but high exposure to traffic-related air pollution.

A Mirror to the Past

While the immediate health risks of aristolochic acid are well established, this study raises a deeper concern: how many other environmental exposures might still be hidden in our genomes, waiting to be uncovered?

“Cancer isn’t always caused by something we’re doing right now,” says Cheng. “Sometimes it’s the result of things we did—or were exposed to—decades ago.”

The findings underline the importance of ongoing surveillance and caution around traditional remedies, particularly those sold online or without verified sourcing. They also reinforce the need for urban pollution control, not just for respiratory health, but potentially for long-term cancer prevention.

What You Can Do

Experts recommend several practical steps in light of the new findings:

  • Avoid unregulated herbal products, especially those purchased through informal channels
  • Check supplement registration with local health authorities before use
  • Monitor air quality, especially in dense urban areas, and use masks or air purifiers during high-pollution periods
  • For people with a family history of lung cancer, early screening with low-dose CT scans may be warranted

A Broader View of Risk

This study reframes our understanding of lung cancer in never-smokers. Far from being a statistical anomaly, it may be the biological legacy of environments, cultures, and chemical exposures that still echo in our DNA.

“We’re learning that lung cancer is not just a smoker’s disease,” says Li. “It’s a disease of our environment—both past and present.”

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