Colorectal cancer is rising sharply in people under 50, and a new study in Nature Medicine points to an unexpected suspect: picloram, a herbicide used widely on US crops and rangelands since the 1960s.

Researchers at the Vall d’Hebron Institute of Oncology analyzed tumor samples from 114 early-onset colorectal cancer patients (under age 50) and 372 late-onset patients (age 70 and older) across ten cohorts.

How Researchers Traced Picloram Exposure

Because direct measurements of lifetime chemical exposure are nearly impossible to collect, the team used an indirect approach—reading the epigenetic “fingerprints” that environmental exposures leave on DNA.

These methylation patterns act like a biological record of what the body has encountered over time.

The findings were striking.

Younger patients showed methylation signatures consistent with significantly higher picloram exposure than older patients.

The association held up across nine independent replication cohorts and remained significant after adjusting for diet, smoking, education, body weight, and other pesticides.

Real-World Evidence Strengthens the Case

To validate the link beyond tumor tissue, researchers analyzed county-level data from 94 US counties over 21 years.

Counties with heavier picloram use had higher rates of early-onset colorectal cancer—an association that survived adjustments for income, poverty, education, employment, and the use of 26 other pesticides.

Of all chemicals tested, picloram showed the most consistent connection.

It works by mimicking plant growth hormones, causing uncontrolled cell growth in weeds.

Residues have been detected in grain and meat byproducts, meaning dietary exposure is plausible.

Because picloram entered widespread agricultural use in the mid-twentieth century, today’s younger patients have been exposed since childhood, while older adults were not, a timeline that fits the data.

The study also confirmed familiar risk factors for early-onset disease: lower adherence to a Mediterranean diet, lower educational attainment, and higher smoking exposure.

But picloram emerged as a new, modifiable environmental factor worth monitoring.

The researchers call for urgent longitudinal studies and a re-examination of regulatory policy.

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Adapted from: Maas SCE, et al. “Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure.” Nature Medicine. 2026. doi:10.1038/s41591-026-04342-5