Each flavor has unique attributes that produce different biological effects
Fruity e-cigarette flavors caused the most genetic alterations (31%), followed by multiple flavors combined (64.3%), compared to sweet (2.9%) and mint (0.9%). Advanced vaping devices called 'mods' showed the most significant and consistent genetic regulation changes, suggesting device design plays a critical role in biological effects.
- Fruity flavors altered 31% of affected genes; multiple flavors combined altered 64.3%
- Advanced vaping devices called 'mods' showed the most significant genetic changes
- 3,124 genes showed altered expression in regular vapers versus non-users
- Two-thirds of genetic changes traced to flavor and device type, not frequency of use
- Cancer was the disease most strongly associated with observed genetic changes
USC researchers found that vaping, particularly with fruity flavors and advanced devices, alters 3,124 genes linked to cancer and other diseases, with flavor and device type explaining 66.6% of genetic changes.
A team of researchers at USC's Keck School of Medicine set out to answer a question that has grown more urgent as vaping has become commonplace: what exactly does inhaling flavored vapor do to the human body at the molecular level? What they found was sobering enough to reshape how regulators might think about e-cigarettes.
The study, published in Frontiers in Oncology, compared genetic activity in 83 people—35 regular vapers, 24 smokers, and 24 people who used neither. The researchers collected cells from inside the cheek of each participant and used RNA sequencing to measure the activity of thousands of genes at once, looking not just at individual genes but at how changes in one gene ripple through entire networks. What emerged from the data was striking: regular vapers showed altered expression in 3,124 genes compared to non-users. That's a substantial disruption of the genetic machinery.
But the real surprise lay in what was driving those changes. When the researchers broke down the data by flavor type and device design, they discovered that two-thirds of the genetic alterations—66.6 percent—could be traced not to how much or how often people vaped, but to what they were vaping and what device they were using. The flavor and the hardware mattered far more than the frequency. Ahmad Besaratinia, the study's lead author and a research professor of public health sciences at Keck, put it plainly: each flavor produced its own distinct biological signature.
The differences were dramatic. Fruity flavors were associated with changes in 31 percent of the affected genes. Multiple flavors combined pushed that to 64.3 percent. Sweet flavors altered 2.9 percent. Mint and menthol came in lowest at 0.9 percent. The advanced devices known as mods—the rechargeable, customizable rigs that many serious vapers prefer—showed the most significant and consistent genetic changes across the board. These newer devices can deliver higher nicotine levels than earlier generations and often contain additives designed to make the experience smoother and more appealing.
When the researchers dug deeper into which biological pathways were being disrupted, cancer emerged as the disease most strongly associated with the genetic changes they observed. Endocrine disorders, gastrointestinal diseases, and neurological conditions followed. The timing of this research is not incidental. The FDA is currently finalizing guidelines on flavored e-cigarettes, and regulators face a genuine tension: weighing potential benefits for adult smokers trying to quit against documented risks to young people. Besaratinia's team found something that complicates that calculus considerably: the molecular changes linked to disease appeared regardless of the user's age.
The implications are already being felt in policy conversations. Besaratinia argues that regulators need to evaluate each flavored product individually, paying close attention to the specific chemicals in the liquid and the design of the device. "Each flavor has unique attributes that produce different biological effects," he said. The current approach—treating all e-cigarettes as a single category—may be too blunt an instrument.
The research team is now conducting follow-up studies to identify which specific chemicals in vaping liquids are responsible for the genetic changes they observed. Once those compounds are identified, policymakers could potentially require manufacturers to eliminate them or reduce their concentrations. It's a path toward harm reduction, though it assumes regulators will act on the evidence. For now, the study stands as a clear signal that the vaping landscape is far more complex than marketing suggests, and that what seems like a simple choice between flavors carries consequences written into the code of human cells.
Notable Quotes
Each flavor has unique attributes that produce different biological effects. Regulators should consider this carefully when evaluating health risks or benefits of each flavored e-cigarette product.— Ahmad Besaratinia, lead researcher, USC Keck School of Medicine
The molecular changes linked to disease appeared regardless of the user's age, complicating the regulatory balance between potential benefits for adult smokers and documented risks to young people.— Ahmad Besaratinia, lead researcher
The Hearth Conversation Another angle on the story
So the study found that flavor matters more than how much someone vapes. That's counterintuitive, isn't it? I would have guessed frequency would be the main driver.
It is counterintuitive, which is partly why the finding is significant. The researchers controlled for frequency and amount—they looked at the data statistically to account for those variables—and still found that two-thirds of the genetic changes came down to what people were actually inhaling and what device they were using. It suggests the chemistry of the product itself is the primary culprit.
And fruity flavors were the worst offenders. Why would fruit flavoring specifically alter so many genes?
That's the question Besaratinia's team is still trying to answer. They don't yet know which specific chemicals in fruity liquids are causing the disruption. But the fact that different flavors produced such different genetic signatures suggests that the chemical composition varies significantly between them. Fruity blends might contain compounds that are particularly reactive in human cells, or they might interact with the lungs and mouth in ways that sweet or minty flavors don't.
The study looked at young, healthy adults. Does that mean older people or people with existing health conditions would be safer?
No, actually. The genetic changes linked to disease appeared across all ages in the study. That's what makes Besaratinia's point about regulation so pointed—you can't say this is only a problem for young people. The molecular damage appears to be age-agnostic. The concern is that these genetic changes are early warning signs. Chronic diseases take decades to develop, but the genes that drive them start changing much earlier.
So we're looking at a long-term health problem that we won't fully understand for years.
Exactly. E-cigarettes are still relatively new. We don't have longitudinal data on what happens to people who vape regularly for twenty or thirty years. What this research does is give us a window into the biological mechanisms—the molecular breadcrumbs—that might lead to disease down the road. It's not proof of harm yet, but it's a very clear warning sign.