Why Are Young People Getting Colon Cancer? Weed Killer May Be Linked” was the social media headline that understandably caused quite a stir, given that epidemiologists have documented a recent disproportionate increase in colorectal cancer in the under-50 age group. The headline was prompted by a paper in Nature Medicine with the title "Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure."
First, we need a little background. DNA is often described as the “blueprint of life,” which is indeed an apt description. It is a giant molecule found in all cells that is composed of individual units called nucleotides linked together in a specific sequence. Segments of DNA, called genes, contain the instructions for making specific proteins that in various ways control everything from physical traits to the numerous chemical reactions that constitute life.
“Epigenetics” is the study of how lifestyle and environmental factors can affect the functioning of genes without changing the sequence of nucleotides that make up the gene. One mechanism involves “DNA methylation,” in which methyl (CH3) groups become attached to genes, with the result being either curbing or increasing their activity. Such methylation is a natural part of the aging process, and its specifics change predictably with age and constitute the basis for determining one’s “epigenetic clock,” a measure of biological aging. A person’s biological age may be more or less than their chronological age.
Epigenetic changes can also result in the proliferation of cancer cells by silencing tumor suppressor genes that act as brakes to stop uncontrolled cell division. Alternatively, they can also activate genes that cause rapid cell division, which is important for a growing body and would normally be turned off in adult cells. If not turned off, the rapid division can lead to malignancy.
The pesticide in question is the weedkiller picloram, used mostly for control of broad-leaved weeds on pastureland, with some use on food crops.
It is important to note that the authors of this paper did not determine pesticide exposure. No urine or blood levels were tested for the presence of any chemicals. Everything was by proxy, in this case, DNA methylation patterns.
DNA methylation patterns have been previously examined for numerous environmental exposures, including air pollutants, smoking, alcohol, coffee, cannabis, and various chemicals, including pesticides. Such patterns are known as “epigenetic fingerprints.” The methylation signature of smoking, for example, is well established, and smokers can be identified by this pattern. In the present study, researchers compared methylation patterns to patterns seen in tumor tissue taken from colon cancer patients. They found a number of methylation patterns similar to those associated with various environmental exposures, with the strongest correlation seen between the DNA methylation pattern in young colon cancer patients and that resulting from exposure to picloram.
The picloram pattern had previously been determined in a 2021 study using blood collected from farmers who had reported using picloram and was assumed to be characteristic of picloram exposure. That is quite a stretch, since farmers use other agrochemicals as well and undoubtedly also have different lifestyle factors from the general population. Also, a methylation pattern seen in a cancer patient may be the consequence of the cancer rather than a reflection of what has caused it. Unlike for smoking, no studies have independently shown that the methylation signature of picloram can be used to identify people who are known to have been exposed to the chemical.
To examine whether any corroborating link between picloram and early-onset colorectal cancer could be found, the researchers looked at government data about the use of pesticides across the U.S. They then selected some counties where pesticide use was documented and where cancer statistics were available and detected a correlation between early-onset colorectal cancer and picloram use.
But without measuring blood levels of a suspect chemical in ailing and healthy subjects, it is not possible to establish a cause-and-effect relationship. It should also be noted that living in a county with high picloram use does not mean that everyone in the county is equally exposed. Exposure may be limited to the surroundings of pastureland. It is also important to note that picloram has limited use and exposure in urban communities, where most of the data on colorectal cancer originates, is unlikely.
Consider also that, as with any pesticide, approval of picloram hinged on carcinogenicity and genotoxicity being ruled out by various laboratory and animal experiments. Furthermore, picloram functions by mimicking the action of auxin, a plant growth hormone regulator, and this mechanism has no plausible connection to any that can drive human carcinogenesis.
Finally, there are far more plausible candidates for the cause of early-onset colorectal cancer than exposure to pesticides. Early antibiotic use that disrupts the gut microbiome, consumption of red and processed meats, high sugar intake, low-fiber diet, obesity, sedentary behavior, exposure to microplastics, ingestion of certain emulsifiers or preservatives are far more likely candidates.
Bottom line? The study linking picloram to colorectal cancer has too many holes to be of any practical significance.
# Reprinted with permission. Dr. Schwarcz’s original article can be found on the OSS website
Lightly edited for clarity and accuracy
Joe Schwarcz
Dr. Joe Schwarcz is Director of McGill University's “Office for Science and Society” which has the mission of separating sense from nonsense. He is well known for his informative and entertaining public lectures on topics ranging from the chemistry of food to the connection between the body and the mind.
