21
May
As Rates Rise in Younger People, Early-Onset Colon and Rectal Cancer Linked to Pesticides’ Altering Gene Expression
(Beyond Pesticides, May 21, 2026) An important study by cancer researchers in Barcelona, Spain at once shows a path forward in illuminating the long-term, multi-generational, health damage from pesticide exposures and demonstrates how extraordinarily dilatory U.S. agricultural regulators are in protecting public health. The study, “Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure,” found a robust association between methylation markers (for gene expression associated with cancer) and exposure to a number of pesticides, with the herbicide picloram having the strongest link. Other pesticides with strong associations include the weedkillers atrazine, glyphosate, nicosulfuron, and insecticide esfenvalerate. Colon cancer is expected to double, and rectal cancer to quadruple, in this young age group by 2030. This sharp contrast between age groups suggests that environmental exposures, rather than strictly genetics, are involved.
The authors are concerned with the alarming rise in early onset colorectal cancer (EOCRC) not only in the highly developed world but also in less-industrialized countries. This increase appears to be connected with age cohorts and the differences in lifestyle and environmental exposures between older and younger cohorts. According to a commentary on the study by researchers from the Dana-Farber Cancer Institute, in the U.S., the incidence of colorectal cancer (CRC) declined steadily in people born between about 1890 and 1950 and then began to rise again. We are now at a point where people born after 1990 are diagnosed at two to three times the rate of those born in 1950.
Early CRC onset is defined as diagnosis before age 50, and among the known risk factors are “family history of colorectal cancer, a history of inflammatory bowel disease (IBD) such as ulcerative colitis or Crohn’s disease, and environmental and lifestyle-related factors such as lack of exercise, obesity, smoking, and alcohol consumption,” according to the Dana-Farber Young-Onset Colorectal Cancer Center.
The Barcelona researchers focused on methylation biomarkers to analyze the generational differences between CRC patients. Methylation is part of a complex system of gene regulation, called epigenetics, that controls which genes are switched off and on in individual cells and tissues. Epigenetic processes do not change genes themselves, but deeply influence the patterns of DNA expression. In recent years methylation status has become the target of extreme scientific interest, because too much or too little methylation in the wrong places affects cancer induction and development, along with chromosomal stability and other important genetic processes. Abnormal methylation is very common in CRC. The researchers developed methylation risk scores (MRSs) based on DNA sites known to influence cancer.
The Barcelona researchers used methylation data from The Cancer Genome Atlas, an archive of cell samples from 33 types of cancers. The archive contains genomic, epigenomic, transcriptomic and proteomic data. The depth and breadth of this data are extremely useful, because while tissue samples over time from conception to adulthood are rarely available, “the epigenome accumulates damage beginning in the gamete’s preconception, continuing through fertilization, prenatal development, and longitudinally throughout the lifetime of an individual,” according to a review by researchers at the University of Michigan. This provides an unparallelled forensic record whose potential is just being realized.
The current study includes MRSs for lifestyle factors such as alcohol consumption, smoking, obesity, birthweight, cannabis use, and education level. Environmental factors include exposures to air pollutants (nitrogen dioxide, PCBs, and particulates) and 14 herbicides and insecticides. The researchers then compare the scores between a set of EOCRC patients and a group of late-onset colorectal cancer (LOCRC) patients.
The data analysis produced 63 MRSs for comparison between age groups. Positive associations emerge between EOCRC and exposure to four pesticides, PCBs, and particulates. In particular, the herbicide picloram stands out, and the significant association with early onset cancer holds up through numerous validation processes. The researchers note that their analysis supports the reliability of using the MRSs as “proxies for true pesticide exposure,” meaning that this method can now be applied with confidence to capture evidence of pesticide exposures that are currently difficult to reach.
In addition, the study examines pesticide use intensity together with EOCRC incidence rates using population data from seven states and found 27 pesticides with significant associations to EOCRC. This gives the researchers an independent measure to compare with and refine the epigenomic data.
Picloram is used mostly on pastures and rangeland to kill plants that compete with food for grazing animals, as well as on wheat, barley and oats, and in forests, rights-of-way, and other noncrop areas. According to EPA’s 2021 Interim Registration Review Decision, about 650,000 pounds of picloram were applied to about fiv million acres a year between 2014 and 2018. Pasture and rangeland accounted for 95% of those acres.
EPA’s only concern with picloram is the possibility that it may be contaminated with the carcinogen hexachlorobenzene. The EPA review found “no acute or chronic risks of concern for mammals” and no acute risk for birds, reptiles or adult honey bees. It did express some concern about chronic risk for bee larvae and birds, but merely notes the need for further studies. The review also reports numerous instances of compost contamination from used animal bedding and manure, with adverse consequences for ornamental plants and some food plants such as sunflowers, tomatoes, cucumber, soybeans and sugar beets. And while the review notes that “picloram and its salts are mobile and persistent,” it finds “no risks of concern” for fish, marine invertebrates or aquatic plants. EPA characterizes picloram as being of moderately to low toxicity to marine life. However, the chemical is not fully evaluated as mixture of chemicals that make up the formulation, as noted by the Australian and New Zealand “Guidelines for Fresh and Marine Water Quality.” The guideline report points to a matter of ongoing exposure, stating: “Picloram does not bind strongly to soil (KOC values of 0.026–100 L/kg). This property (combined with its low volatility, high solubility and high persistence) means picloram has a high potential to leach to groundwater and enter surface water (USEPA 1995, EFSA 2009, Tu et al. 2001, APVMA 2015, NCBI 2020). Once picloram has reached groundwater, it is unlikely to degrade, even over several years (USEPA 1995).” On a historical note, a 4:1 mixture of the 2,4-D and picloram herbicides, known as Agent White, was used as a jungle defoliant in Viet Nam war, along with Agent Orange (a mixture of 2,4-D and the herbicide 2,4,5-T).
Picloram was synthesized by Dow Chemical Company chemists in the early 1960s and first registered by EPA in 1964. The European Union recently extended its registration approval until 2028. Picloram acts by binding to cell receptors for the most common plant growth hormone, indole-3-acetic acid (IAA), producing chaotic cell division and plant death. It is not correct to assume, as both regulators and pesticide corporates have done, that IAA pertains only to plants. IAA is ingested by mammals and produced by gut microbiota. According to a 2025 review in The FASEB Journal, IAA has numerous effects on human health, including exacerbating chronic kidney disease, liver stress and cardiovascular disease, but also has some potential protective effects against oxidative stress, inflammation and lipid metabolism. Picloram’s effects on the presence and activity of IAA in nontarget organisms are largely unknown, but as with the weed killer glyphosate’s effects on everything from cancer to reproduction to brain health, the failure to consider unintended consequences of pesticides including picloram rings loud and clear.
The coincidence of picloram and the reversal of the CRC curve in the early 1960s is highly suggestive. The Barcelona authors note that, “If the use of picloram in crops started in the mid and late twentieth century, then current patients with LOCRC were not exposed during their childhood, whereas cases of EOCRC were and have been for a longer part of their lives, which could explain our results.”
Dana-Farber experts point out in their online commentary that the study has several limitations. In its population-level analyses of pesticides, it relied on self-reported exposure data. The epigenomic data was derived from a small sample from The Cancer Genome Atlas of patients who were all males of European ancestry. Further, the MRSs for pesticide exposures are very new compared to those proven to reflect smoking exposure. However, in a parallel perspective in Nature, they wrote that the Barcelona study “lends support to the growing concerns regarding the role of pervasive environmental contaminants on early-onset cancer risk. In reality, picloram is only one of innumerable synthetic chemicals introduced during the post-World War II industrial expansion, as growth of the petrochemical industry in the 1950s drove their large-scale production and global environmental dissemination.”
It is difficult to calculate unintended consequences given that many diseases, including cancers, take decades—even generations—to manifest after early exposures to toxic chemicals. But the consequences are starting to be seen in the preserved cellular record, and with this knowledge comes the responsibility to adopt regulatory restrictions that stop causing the harms.
A further consideration in the context of this forensic resource is parallel emerging evidence that epigenetic changes to germ cells—sperm and eggs—acquired at any phase of life are transmissible to ensuing generations. Research by Michael Skinner, PhD, at Washington State University establishes that in mice exposed to the fungicide vinclozolin in the first generation produced reproductive abnormalities in the mice’s great-grandchildren. Dr. Skinner’s team has now identified 19 chemicals that produce transgenerational epigenetic damage, including eight pesticides. These changes involve DNA methylation. More ominously, Dr. Skinner’s recent work has extended the timeline to the 20th generation, which continues to show “the generational stability of epigenetic inheritance over twenty generations in a mammalian model system; however, new pathology in later generations involving parturition abnormalities was also observed. The generational stability of transgenerational effects observed in this study has implications for human health, particularly regarding environmental toxicant exposures, reproductive health disorders, and disease susceptibility.”
Taken together, the Barcelona evidence and its innovative methodology, the existing epidemiological record, and the striking transgenerational evidence of harm by pesticides creates a moral imperative, one that the Barcelona authors call “a compelling rationale for addressing lifestyle and environmental exposures to mitigate EOCRC risk, highlighting the importance of both personal and policy-level interventions.”
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Sources:
Epigenetic fingerprints link early-onset colon and rectal cancer to pesticide exposure
Maas et al.
Nature Medicine 2026
https://www.nature.com/articles/s41591-026-04342-5.pdf
Dana-Farber Experts Offer Perspective on Link Between Pesticide Exposure and Early-Onset Colorectal Cancer
Dana-Farber Cancer Institute April 30, 2026
https://www.dana-farber.org/newsroom/news-releases/2026/dana-farber-experts-offer-perspective-on-link-between-pesticide-exposure-and-early-onset-colorectal-cancer
Studies Find Genetic and Epigenetic Effects from Pesticide Exposure, Threatening Future Generations
Beyond Pesticides, March 3, 2026
https://beyondpesticides.org/dailynewsblog/2026/03/studies-again-find-genetic-and-epigenetic-effects-from-pesticide-exposure-threatening-future-generations/
Beyond Pesticides
Daily News Blog Archive – Epigenetics
https://beyondpesticides.org/dailynewsblog/category/diseasehealth-effects/epigenetic/
https://beyondpesticides.org/dailynewsblog/category/diseasehealth-effects/epigenetic-effects/
Epigenetics and the exposome: DNA methylation as a proxy for health impacts of prenatal environmental exposures
Colwell et al.
Exposome 2023
https://academic.oup.com/exposome/article/3/1/osad001/7008330
Gateway on Pesticide Hazards and Safe Pest Management
Beyond Pesticides
https://www.beyondpesticides.org/resources/pesticide-gateway
Picloram
Beyond Pesticides Gateway on Pesticide Hazards and Safe Pest Management
https://www.beyondpesticides.org/resources/pesticide-gateway?chemfind=picloram
Picloram
Interim Registration Review Decision
Case Number 0096
September 2021
Docket Number EPA-HQ-OPP-2013-0740
www.regulations.gov
