- A new study suggests that environmental and lifestyle exposures, such as diet, smoking, and chemical exposure, may contribute to early-onset colorectal cancer.
- The study confirmed known risk factors, like tobacco use and diet, while also identifying a new association with the agricultural herbicide picloram.
- Regions with higher picloram use showed higher rates of early-onset colorectal cancer, suggesting a possible environmental link, though not proving causation.
- The findings highlight how cumulative lifetime exposures, known as the ‘exposome’, may help explain rising cancer rates in younger adults and could inform future prevention strategies.
Early onset colorectal cancer describes a diagnosis of colorectal cancer in adults under 50. Previously considered a disease of older age, colorectal cancer is rising globally at an alarming rate in younger adults, with a 1.4% annual increase in incidence reported.
Evidence suggests that in many areas colorectal cancer is increasing in younger adults faster than older adults, and roughly 1 in 5 diagnoses occurs in someone under the age of 55. Research also highlights that colorectal cancer is now the leading cause of cancer-related death among males and females under age 50.
While the incidence of early onset colorectal cancer rises, the drivers of this trend remain poorly understood. Previous research has suggested the potential role of the exposome. This term refers to all the exposures a person experiences throughout their life and how those exposures affect their health.
Now, a new study published in Nature Medicine, suggests that epigenetic changes, or ‘molecular footprints’, associated with dietary patterns, smoking, and pesticide exposure may help explain the rising incidence of early onset colorectal cancer.
Researchers from the Vall d’Hebron Institute of Oncology (VHIO) focused on the possible association between the exposome and colorectal cancer. However, rather than measuring exposures directly, the team examined epigenetic changes, specifically DNA methylation.
These are chemical modifications that influence gene expression without altering the DNA sequence itself. Experts often compare epigenetic marks to annotations in a book; they do not change the text but influence how it is read.
The study analyzed DNA methylation patterns in those diagnosed with colorectal cancer before and after age 50. The researchers then created epigenetic risk scores reflecting exposure to various environmental factors.
They found distinct epigenetic signatures linked to dietary patterns, tobacco use, and environmental exposures.
Lead study author José Seoane, PhD, Head of the VHIO Computational Biology Group, explained to Medical News Today how epigenetic signatures and risk scores make a useful tool for studying the exposome.
“Epidemiologists have been studying how our methylation is changed by the environment for quite a while. We have a lot of EWAS (epigenetic wide association studies) that identifies methylation locus associated with an exposure,” Seoane explained.
“We get this information and build signatures of how this signal is changing in tumor tissues, therefore we are able to retrieve a sort of ‘history’ of exposure from the methylation data,” he said.
The study confirmed known risk factors and notably found a new association with a widely used agricultural herbicide.
“In this study we identify an association between early onset colorectal cancer and some environmental exposures, studying their epigenetic profiles,” Seoane told MNT.
“We identify that smoking, diet and a pesticide named picloram are associated with early onset colorectal cancer.”
— José Seoane, PhD
Using U.S. population data, the researchers observed that counties with higher picloram use also had higher rates of early onset colorectal cancer, even after accounting for socioeconomic factors and other pesticides.
Further analysis revealed that tumors linked to higher picloram exposure showed different molecular characteristics. This included fewer variations in the APC gene, a key gene involved in colorectal cancer development.
This suggests that environmental exposures could contribute to cancer development through mechanisms beyond traditional genetic alterations.
However, the researchers emphasize that these findings show an association, not proof of causation. As such, more studies are necessary to confirm whether picloram directly contributes to early onset colorectal cancer development.
“As the link between smoking and diet and early onset colorectal cancer has been already established by epidemiological studies, we were expecting to have it in our hits,” Seoane told MNT.
The pesticide with the strongest link
“Picloram was a surprise because it was never associated with cancer. In order to validate this, we correlate a database of incidence of early onset colorectal cancer in U.S. counties with a database of pesticide use in the same counties, and picloram was again the most significant hit, showing strongest association that other pesticides, for example glyphosate.”
— José Seoane, PhD
“Of course, we should be cautious, because both analyses are observational, so further research should be done to establish causal links,” he added.
While further research is still needed, this study highlights the possibly larger role that environmental and lifestyle factors may play in cancer risk than was previously understood, particularly for younger individuals.
The findings also demonstrate the potential role of epigenetics as a tool for tracking lifetime exposures and identifying modifiable risk factors. MNT asked Seoane if there are modifiable risk factors that people should be more aware of.
“Of course, and I think this is one of the most important messages of this work: People are aware that diet is associated with cardiovascular diseases and smoking is associated with lung cancer,” Seoane said.
“Here we identify also that both diet and smoking are associated with early onset colorectal cancer. So it is reasonable to say that better diet and quitting smoking should lower the risk of colorectal cancer. Picloram is more complex, because if causal analysis confirms our results, very likely this should be regulated by governments.”
— José Seoane, PhD
The study authors also suggest that their findings could support improved prevention strategies, public health policies targeting environmental exposures, and earlier identification of individuals at higher risk.
By linking epigenetic changes to real-world factors, this study may offer a new framework to help explain the rising burden of colorectal cancer in younger populations.
