Changes caused by diet, smoking, and exposure to pesticides are linked to the development of colorectal cancer in people under 50

I enjoyed reading the study; it is innovative work with careful analyses. The scientific value is clear. Using DNA methylation as a proxy for past exposures is an interesting and innovative approach. The authors also attempt to replicate their findings across different cohorts and datasets, which is essential.

However, it is one thing to conduct a brilliant scientific study, but it is quite another for it to carry sufficient weight to change the risk assessment of pesticides.

The value for regulatory evaluations is less clear. This study shows associations, not causation. This is a key point. The signal for picloram is interesting, but exposure was not directly measured in the subjects. Therefore, we cannot conclude that picloram causes these cancers.

Furthermore, we must consider the nature of the substance itself. Picloram has not been found to have carcinogenic properties in regulatory tests. Historically, however, it was often contaminated with carcinogenic substances such as hexachlorobenzene. It is possible that any observed effects were due to this contamination rather than picloram itself, a problem which should have largely been resolved in modern manufacturing. It is always important to remember that real-world exposures involve not just the active ingredient, but also co-formulants and potential contaminants.

Overall, this is a fascinating and well-done study that raises a plausible hypothesis. Nevertheless, more work is needed, specifically with direct exposure data and longitudinal designs, before making causal claims.