Epigenetic fingerprint ties pesticide to early-onset bowel cancer

A new culprit – pesticide exposure – has emerged alongside known risk factors smoking and diet as a possible contributor to the rising incidence globally of early-onset bowel or colorectal cancer.

A study by scientists in Spain identified a new association with a widely used agricultural weedkiller, picloram, in which regions with higher use of the herbicide showed higher rates of cancer.

Previous research had spotlighted the potential for lifestyle and lifetime exposure to environmental factors (known as the exposome) to affect a person’s health.

The new study, led by researchers at the Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, and published in the journal Nature Medicine, looked into the possibility of an association between the exposome and bowel cancer by examining epigenetic changes, so-called “molecular fingerprints”, specifically DNA methylation. These are chemical modifications that influence gene expression without altering the DNA sequence itself.

The study analysed DNA methylation patterns in people diagnosed with bowel cancer before the age of 50, and older, drawing upon US population data.

“If we imagine the genome as a book, epigenetic marks don’t change the text but function like post-it [notes] or markers that indicate which chapters should be read and which should be skipped,” explained the study’s lead author, Dr Jose A. Seoane, who heads the VHIO Computational Biology Group.

“Furthermore, these post-its can be added or removed depending on the environment and lifestyle – diet, stress or exposure to toxins – influencing how the same book is interpreted over time.

“We explored the components of the exposome that might contribute to the development of colorectal cancer in young people compared to colorectal cancer diagnosed at older ages, using epigenetic markers.”

The researchers created epigenetic risk scores reflecting exposure to various environmental factors. A higher picloram-related methylation score was associated with bowel cancer diagnosed in people under the age of 50, compared with bowel cancer diagnosed at age 70 or older.

The authors noted that picloram was first registered as a herbicide in the US in the 1960s, meaning younger generations may have been exposed to it for a larger proportion of their lives. People exposed to it as children would be younger than 70 today, possibly explaining why the association was seen mainly in cases of early-onset disease.

While the study confirmed known risk factors for bowel cancer – namely, smoking and diet – it, notably, found a new association with picloram, revealing that tumours linked to higher picloram exposure showed different molecular characteristics.

“We observed that tumours with high exposure to the pesticide had fewer mutations in the APC gene, a key gene in colorectal cancer that regulates the Wnt pathway, which is related to cell growth,” reported Dr Seoane.

“This suggests that exposure to picloram could promote cancer development even without mutations in the APC gene.”

Bowel cancer is the third most common cancer worldwide, and the second leading cause of cancer-related deaths globally. It is rising at a faster rate among adults under age 50 and is now the leading cause of cancer-related death for both men and women in that age cohort.

The researchers cautioned that their findings were correlational and not causal.

They suggested further research was necessary to confirm whether exposure to picloram was behind early-onset colorectal cancer development.

“In conclusion, our findings not only provide exposome traits based on epigenetic fingerprints that could be contributing to the development of colorectal cancer, specifically in early-onset colorectal cancer [EOCRC], but also lay a solid foundation for addressing environmental exposures and lifestyle-related factors to reduce EOCRC risk, highlighting the importance of promoting preventive interventions at both the individual and public policy levels,” Dr Seoane said.