Chemical Marks on DNA Link Diet, Smoking and a Herbicide to Colorectal Cancer in the Under-50s

Colorectal cancer is becoming more common in people under 50, yet their tumours often show no obvious genetic differences from those found in older patients. A study led by José A. Seoane at the Vall d'Hebron Institute of Oncology in Barcelona suggests part of the answer lies not in the DNA sequence but in chemical marks left on it by a lifetime of exposures. The work was published on 21 April 2026 in Nature Medicine.

The team studied epigenetics, biological mechanisms that switch genes on or off without changing the DNA sequence. One form, DNA methylation, attaches small chemical tags to DNA. Seoane compares the genome to a book in which these tags act like sticky notes marking which chapters are read and which are skipped, and which can be added or removed depending on diet, stress or exposure to toxins. The researchers built risk scores from methylation patterns to reflect exposure to lifestyle and environmental factors, developed them using data from a large cancer genome database and validated them in nine further independent patient groups.

Comparing patients diagnosed before and after 50, the team found significant differences in epigenetic signatures tied to diet, tobacco and pesticide exposure. A particularly clear signal stood out for the herbicide picloram. Using U.S. cancer registries alongside county-level pesticide-use data, the researchers found that early-onset colorectal cancer was significantly associated with picloram use, even after accounting for social and demographic factors and other pesticides.

Picloram has been in use since the mid-1960s. People now diagnosed after 50 would not have been exposed to it in childhood, while younger patients may have encountered it across a longer part of their lives. Colorectal cancer is the world's third most common cancer and the second leading cause of cancer death; about 90% of cases and deaths occur in people over 50.