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Study links herbicide picloram to increased early-onset colorectal cancer risk using epigenetic analysis

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Study Links Herbicide to Rising Cases of Early-Onset Colorectal Cancer

A new study published in Nature Medicine has used patterns of DNA methylation—often described as "epigenetic fingerprints"—to analyze environmental exposures in patients with colorectal cancer. The research compared these patterns between younger and older patients, identifying a specific herbicide as significantly associated with an increased risk of early-onset disease.

The herbicide picloram was identified as significantly associated with early-onset colorectal cancer (EOCRC) risk in the discovery cohort analysis.

Study Design: An Epigenetic Investigation

Researchers developed Methylation Risk Scores using specific DNA methylation sites as proxies for 29 lifestyle and environmental factors. These factors included 11 lifestyle traits, 4 air pollution measures, and 14 pesticide exposures.

The study compared exposure patterns in 31 patients under 50 years old (early-onset colorectal cancer/EOCRC) with 100 patients aged 70 or older.

Findings were validated through a meta-analysis of 9 independent cancer cohorts totaling 83 EOCRC and 272 late-onset colorectal cancer patients. Additional validation came from comparing methylation patterns with gene expression changes in human stem cell-derived cardiomyocytes exposed to pesticides.

Finally, a population-level analysis used 21 years of data from 94 US counties, matching pesticide use intensity with local colorectal cancer rates.

Key Findings

  • In the discovery cohort, high picloram Methylation Risk Scores showed a strong association with early-onset cancer.
  • The meta-analysis of pooled datasets confirmed the picloram association.
  • US county data analysis showed higher picloram use intensity correlated with higher colorectal cancer rates in younger people.
  • Molecular analysis revealed picloram-associated tumors had different biological characteristics, including lower APC gene mutation rates (74% vs 90% in older patients).
  • Picloram-associated tumors also showed different Wnt/β-catenin signaling patterns compared to typical age-associated colorectal cancers.

Context and Significance

Colorectal cancer is the second leading cause of cancer-related deaths worldwide. Of particular concern is early-onset colorectal cancer (diagnosed before age 50), which has increased in prevalence in recent decades.

The study represents the first identification of picloram as a potential environmental factor associated with EOCRC risk.

Researchers note the findings do not prove causation but suggest a clear need for further investigation. The study also highlights potential generational differences in environmental exposures between older and younger colorectal cancer patients.