Colon Cancer
- 1 day ago
- 3 min read
In a recent episode of the All in Podcast, David Friedberg discussed the new paper in Nature Medicine by Dr. Maas and colleagues which paints a modern picture of colon cancer and the why? It is super important as a stand alone study as well as a blueprint for further future analysis of chemical disease associations across the 80,000 chemicals in circulation. (Dept Tox Subst)
Colorectal cancer used to be a disease of age. Now it’s a disease of timing.
Over 20 years: >80% increase in people under 50.
That’s not drift. That’s signal.
So what changed?
A research group in Barcelona looked past genetics into the epigenome. Not the code.
The instructions on how the code is read. The marks left by the exposome, the environment.
They compared tumor cells from younger vs older patients. What they found: Young patients’ tumors carry a different epigenetic fingerprint. Not just mutations. Reprogramming.
This suggests:
· Cancer risk is being shaped earlier in life
· Environmental inputs are leaving marks
· Those marks change gene expression long before disease appears
Think:
· Diet (ultra-processed, low fiber)
· Microbiome disruption
· Chronic inflammation
· Metabolic stress
Not one cause. A pattern. Genes load the gun. Environment sets the timing.
In this case, a chemical, picloram, is the trigger pull.
The unsettling part: These changes may start decades before diagnosis.
Childhood. Adolescence. Early adulthood.
We’re not seeing more cancer because we’re older.
We’re seeing it because biology is being pushed earlier.
Same disease. Shifted timeline. Clinical implication: Stop thinking detection. Start thinking trajectory.
Trend the terrain:
· Inflammation
· Metabolic markers
· Gut integrity
· Diet quality
Because by the time cancer shows up, the story has already been written.
Early cancer is not bad luck. It’s early exposure.
The Abstract: "The incidence of colorectal cancer (CRC) is rising rapidly in people younger than 50 years. Although this increase parallels shifts in lifestyle and environmental factors—collectively termed the exposome—whether these are indeed linked to the development of early-onset CRC (EOCRC) remains uninvestigated. Due to limited exposome data in most cancer cohorts, we constructed weighted methylation risk scores as proxies for exposome exposure to pinpoint specific risk factors associated with EOCRC compared to late-onset CRC (LOCRC) patients diagnosed at ≥70 years. Our analysis confirmed previously identified risk factors, including educational attainment, diet and smoking habits. Moreover, we identified exposure to the herbicide picloram as a new risk factor (adjusted P = 4.4 × 10−4) in the discovery cohort (31 EOCRC versus 100 LOCRC), which was replicated in a meta-analysis comprising nine CRC cohorts (P = 3.1 × 10−3; adjusted P = 1.5 × 10−2; 83 EOCRC versus 272 LOCRC). Subsequently, we analyzed population-based data from 94 US counties over 21 years and validated the association between picloram use and EOCRC incidence (P = 4.52 × 10−4), which remained significant after adjusting for socioeconomic factors and other pesticide use. These findings highlight the critical role of the exposome in EOCRC risk, underscoring the urgency for targeted personal and policy-level interventions." (Maas et. al. 2026)
My comments from the David Friedberg's analysis and the apple transcript: A research group in Barcelona conducted a study comparing the epigenetic patterns, essentially gene expression, of tumor cells from patients under 50 versus those over 70. The goal was to identify environmental exposures linked to these differences. When the body encounters environmental inputs, food, chemicals, or other factors, certain genes are switched on or off. By analyzing RNA, researchers can see which genes are actively producing proteins and which are not, offering a snapshot of how cells respond to those exposures. Using colon cancer samples from The Cancer Genome Atlas, the team compared gene expression profiles between younger and older patients with colon adenocarcinoma. This allowed them to connect specific environmental influences to patterns seen in younger individuals developing cancer, where risk is typically lower, versus older individuals, where risk is expected to be higher. They adjusted for a wide range of variables, including diet, body weight, alcohol use, birth weight, and gender. Across all these factors, one signal stood out: exposure to a pesticide called Picloram. Originally developed by Dow Chemical Company in 1963, picloram is a synthetic plant hormone analog used to kill weeds by driving uncontrolled growth. It has been widely applied in agriculture, especially on grazing land, as well as along roads, railways, and industrial corridors. A key concern with picloram is its persistence: it breaks down slowly, can remain in soil and water for extended periods, and is capable of leaching into groundwater, making it a long-lasting environmental exposure.
(From All-In with Chamath, Jason, Sacks & Friedberg: SpaceX-Cursor Deal, SaaS Debt Bomb, New Apple CEO, SPLC Indictment, Colon Cancer Spike, Apr 24, 2026
Dr. M
