Pesticide exposure could explain the increase in colorectal cancer cases in those under 50 years old

BarcelonaExposure to pesticides is associated with the appearance of colorectal cancer in people under 50 years of age. Specifically, researchers from the Vall d’Hebron Institute of Oncology (VHIO) have discovered a significant association between a widely used herbicide, picloram, and a substantial increase in the number of cases of this disease in young patients in recent years.

In a study published in Nature Medicine, the Catalan researchers suggest that contact with this chemical product, as well as diet and lifestyle, leave traces in DNA that could explain why this tumor appears prematurely.

The work provides new evidence on the role of the exposome, a concept that emerged just 20 years ago and focuses on the set of factors to which we are exposed throughout life and which can explain the rise in chronic diseases, such as diabetes, obesity, or cancer. Precisely, among the factors suspected of contributing to making us ill are certain chemical products, some present in clothing, cosmetics, or food.

The ‘post-it notes’ in the genome

Colorectal cancer is the third most common tumor in the world and the second leading cause of cancer death. Traditionally, it was a disease associated with aging and, in fact, currently nine out of ten cases are diagnosed in people over 50 years old. However, in recent years, oncologists have noted a significant increase in cases of this disease in people under 50 years old. And in some countries, such as the USA, it is already the leading cause of cancer death in men and the second in young women.

The causes of this increase in the incidence of

colorectal tumors with early onset are not clear. Scientists had pointed to lifestyle, diet, smoking, and environmental exposure to toxins, but these factors had not been precisely associated with cancer risk.

To shed light on this association, VHIO researchers have studied epigenetic marks, imprints on DNA that act as "post-it notes or markers that indicate in the genome book which chapters to read," says José Antonio Seoane, head of the VHIO's Computational Biology Group. These post-it notes can be removed or added depending on diet, stress, exposure to toxins, which influences how the book is interpreted over time, adds the researcher, co-author of the work.

The VHIO team analyzed which exposome factors could be contributing to the development of colorectal cancer in individuals under and over 50 years old based on these epigenetic marks and generated risk scores. They then compared the scores obtained in each of the two groups of patients with this tumor.

"We observed that there were significant differences in the epigenetic signatures associated with diet, smoking, and pesticide exposure," says Silvana Maas, a postdoctoral researcher at the VHIO's Computational Biology Group and first author of the work. "Among pesticides, there was a very clear signal of correlation between exposure to the pesticide picloram and early-onset colorectal cancer," she highlights.

Subsequently, VHIO scientists studied this relationship in population databases of people with cancer and pesticide use by county in the United States and observed that "the incidence of early-onset colorectal cancer was significantly associated with the use of picloram, even after adjusting for sociodemographic factors and exposure to other pesticides," says Maas.

Association, not causation

Picloram is a widely used herbicide in cereal crops that began to be used in the mid-1960s. The authors of the study point out that individuals under 50 years of age who are now developing colorectal cancer at an early age may have been exposed to this chemical product since childhood, and that this could explain the differences in the onset of early tumor development.

For Robin Mesnage, a researcher at King's College London, who was not involved in this work, the study's results show association, not causation: "Exposure to picloram has not been directly measured in people, therefore, it cannot be concluded that it causes cancer." This researcher recalls that this herbicide has never been found to have carcinogenic properties, but that years ago it had been contaminated with substances that were, such as hexachlorobenzene. "It is possible that any observed effect was due to this contamination," he states in statements to the UK Science Media Center. The problem, he says, "should have been largely resolved with modern manufacturing."

More studies will be needed to conclude whether, as the research community suspects, pesticides could be acting as endocrine disruptors, altering the gut microbiota and triggering inflammation.