Common herbicide linked to early onset of colon cancer

Colon cancer used to be something people mostly worried about after 50. It was the disease your doctor started screening for at a certain age, the kind that came with a lifetime of accumulated risk. But that's not what's happening anymore. Something has shifted. And a new study published in Nature Medicine might finally offer one of the clearest clues yet as to why.


Researchers have identified epigenetic fingerprints that link early-onset colorectal cancer to pesticide exposure, specifically to a herbicide called picloram, which has been sprayed on crops across the United States and other countries for decades. The findings are striking not just because of what they found, but because of how they found it. Instead of relying on patients to report their own chemical exposure, which almost nobody accurately can, the researchers essentially read the chemical history off the DNA itself.


Globally, colorectal cancer ranks as the third most common cancer type and the second leading cause of cancer-related death. As an aging-associated disease, roughly 90% of worldwide cases and deaths occur in people over 50. But that long-established pattern is breaking. Worldwide cancer registries have reported a disproportionate increase in early-onset colorectal cancer, generally defined as colorectal cancer diagnosed in people younger than 50.

What the DNA remembers

That's where this new research gets genuinely interesting. The team behind the study used what they call methylation risk scores,essentially, patterns of chemical modification on DNA that act as a kind of molecular diary of everything a person has been exposed to over their lifetime. Smoking leaves a mark. Diet leaves a mark. And apparently, certain pesticides do too.


Using data from 94 US counties tracked over 21 years, the researchers validated an association between picloram use and early-onset colorectal cancer incidence, and that association remained significant even after adjusting for socioeconomic factors and other pesticide use.


The researchers identified exposure to the herbicide picloram as a new risk factor in their discovery cohort, which was subsequently replicated in a meta-analysis comprising nine colorectal cancer cohorts.


Picloram is a broadleaf herbicide that's been registered for use in the US since 1964. Its mechanism of action as an herbicide relies on its ability to mimic plant growth hormones called auxins, leading to abnormal tissue stimulation, root deterioration, and eventually plant death. It's widely used on rangelands, pastures, and grain crops,which is precisely where it ends up in the food chain. Dietary exposure to picloram residues is plausible, as it has been found in grain and meat byproducts, and the effects of long-term use on human health have not been described until now.


The researchers offer a compelling generational explanation for why picloram might be specifically affecting younger patients. If the use of picloram in crops began in the mid and late twentieth century, then current older patients with late-onset colorectal cancer were not exposed during their childhood, whereas cases of early-onset colorectal cancer were — and have been for a longer portion of their lives. In other words, the generation now developing colon cancer in their 30s and 40s grew up alongside the widespread adoption of this chemical.

Not just Picloram

The study doesn't implicate picloram alone. The researchers also found evidence for associations between early-onset colorectal cancer and exposure to glyphosate, esfenvalerate, nicosulfuron, and atrazine. Glyphosate is already the subject of enormous controversy. It has been categorized as "probably carcinogenic to humans" by the International Agency for Research on Cancer. Atrazine is one of the most heavily used herbicides in American corn production, and while the European Union banned it back in 2004, it remains approved for use in the United States.


The study also confirmed what researchers have long suspected about lifestyle factors, lower Mediterranean diet adherence, lower educational attainment, and greater smoking exposure were all associated with early-onset colorectal cancer. None of that is especially surprising. But the pesticide findings represent genuinely new territory.


What makes all of this harder to sit with is the sheer scale of herbicide use worldwide. These aren't obscure, fringe chemicals. They're embedded in industrial agriculture across North America, parts of South America, Australia, and increasingly in South and Southeast Asia. The colon cancer rise in younger adults isn't a uniquely American story either, it's been documented across multiple continents, including regions with very different diets and genetic backgrounds.