Epigenetic Fingerprints Link Early-Onset Colon and Rectal Cancer to Pesticide Exposure
A fresh study published in Nature Medicine has identified a significant association between exposure to the herbicide picloram and increased risk of early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed in individuals under 50 years of age. The research, conducted by an international team led by Silvana C. E. Maas, used epigenetic markers as proxies for lifetime environmental exposures to uncover this link.
Scientists analyzed DNA methylation patterns in tumor and blood samples from 31 EOCRC patients and 100 late-onset colorectal cancer (LOCRC) patients diagnosed at age 70 or older. Through this approach, they constructed weighted methylation risk scores to reflect exposome exposure—encompassing lifestyle, diet, and environmental factors—and pinpointed specific risk factors associated with early-onset disease.
The analysis confirmed previously established risk factors for EOCRC, including lower educational attainment, certain dietary patterns, and smoking history. More notably, it identified exposure to picloram—a widely used herbicide for controlling woody plants and broadleaf weeds—as a novel risk factor. In the discovery cohort, this association showed an adjusted P-value of 4.4 × 10−4.
To validate these findings, researchers performed a meta-analysis across nine colorectal cancer cohorts, encompassing 83 EOCRC and 272 LOCRC cases. The association between picloram exposure and EOCRC remained statistically significant, with a P-value of 3.1 × 10−3 and an adjusted P-value of 1.5 × 10−2.
Further strengthening the evidence, the team examined population-based data from 94 U.S. Counties over a 21-year period. This ecological analysis revealed a significant correlation between county-level picloram use and incidence of early-onset colorectal cancer (P = 4.52 × 10−4). The association persisted even after adjusting for socioeconomic status and other pesticide exposures, suggesting an independent contribution of picloram to EOCRC risk.
Experts responding to the study emphasized its innovative use of epigenetic biomarkers to infer historical exposome influences in the absence of direct exposure measurements. However, they cautioned that the findings demonstrate association, not causation. As noted in expert commentary, “more work is needed, specifically with direct exposure data and longitudinal designs, before making causal claims.”
Colorectal cancer remains a major global health concern, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide. While approximately 90% of cases occur in individuals over 50, incidence rates among younger adults have been rising rapidly in recent decades—a trend that parallels shifts in lifestyle and environmental exposures.
The study underscores the importance of the exposome—the cumulative measure of environmental influences over a lifetime—in shaping cancer risk, particularly for early-onset disease. Researchers suggest that identifying specific environmental contributors like picloram could inform both personal risk reduction strategies and broader policy interventions aimed at regulating pesticide use.
As scientific understanding of epigenetic mechanisms advances, such biomarker-based approaches may offer valuable tools for uncovering hidden environmental drivers of disease, especially in populations where historical exposure data are scarce.