Pesticides are one of the great unresolved issues in global public health. For decades, environmentalists, doctors and researchers have raised concerns about their impact on the human body, not only in those who handle them directly, but also in those who inhale them, ingest them through food or absorb them from contaminated water and soil. Yet establishing a direct causal link between environmental exposure to these substances and the development of tumors has proven extraordinarily difficult: the mixtures involved are complex, the exposures prolonged and difficult to measure, and traditional experimental models often fail to replicate real-world conditions.
Now, a new and important study published on Nature Health by an international team including researchers from the IRD (French National Research Institute for Sustainable Development), the Institut Pasteur, the University of Toulouse and the Peruvian National Institute for Neoplastic Diseases (INEN) brings concrete and unprecedented evidence that this link exists and is measurable.
The study
The heart of the study is a high-resolution geospatial model, developed to map the risk of environmental exposure to pesticides across the entire Peruvian territory. Peru was not chosen by chance: it combines intensive agriculture, a great variety of ecosystems (from the desert coasts of the Pacific to the Andean highlands to the Amazon forests) and profound social inequalities that disproportionately expose indigenous and peasant communities to the chemicals used in the fields.
The researchers examined 31 active ingredients including insecticides, fungicides and herbicides commonly used in Peru, none of which are classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC). The model simulated, month by month over six years (from 2014 to 2019), how these substances are dispersed in the environment through water runoff, soil type, topography and precipitation, building a grid with 100 meter by 100 meter cells that covers almost the entire national territory.
The result is a map that shows, with precision never before achieved on a national scale, where the risk of cumulative exposure to pesticides is highest.
The most critical areas are concentrated on the Andean highlands and along the western slopes, where limited rainfall favors the accumulation of substances in the soil. Contamination extends up to 30-50 kilometers beyond farmland, reaching communities that have no direct contact with agriculture.
Once the environmental map was built, the researchers overlaid it with data from 158,072 primary cancer cases recorded by INEN between 2007 and 2020, geocoded and verified with national censuses to ensure that each patient had resided in the indicated area for at least five years before diagnosis.
The most significant methodological innovation of the study, however, concerns the way in which the tumors were classified. Instead of grouping them by organ of origin, as is traditionally done, the researchers stratified them according to their line of embryonic development, i.e. based on the type of cell from which they derive. This approach, based on cellular ontogeny, has allowed geographical patterns to emerge that conventional classifications tended to hide.
The result was clear: in areas with greater environmental risk of exposure to pesticides, the incidence of tumors was significantly higher. The researchers identified 436 hotspots spread across Peru, where the relative risk of developing cancer was on average 150% higher than expected. The highest peaks come at a risk almost ten times higher than the national average.
Of all the affected organs, the liver emerges as the most significant and best documented site. This is no surprise, the liver is the main organ responsible for the metabolism of toxic substances in the human body, the first to receive and process foreign compounds absorbed from the intestine. For this reason it is considered by scientists to be a true “sentinel organ” of environmental exposure to chemical carcinogens.
To understand what was happening on a biological level, the research group analyzed liver tissue samples taken from 36 patients living in risk areas. Transcriptosmic analyzes – which study which genes are active or silenced in a tissue – have revealed a molecular signature characteristic of exposure to non-genotoxic substances, i.e. chemical agents that do not directly damage DNA but interfere with cellular regulatory mechanisms. This signature was present mainly in healthy liver tissue, the one surrounding the tumor, which suggests that the biological alteration precedes malignant transformation, an early signal, imprinted in the cells before the cancer manifests itself.
The same signature was not found in cohorts of liver cancer patients from France, Taiwan and Turkey, confirming that this is something specific to pesticide-exposed populations in Peru.
How pesticides work
One of the most interesting and worrying aspects of the study concerns how pesticides appear to work. The 31 active ingredients considered are not carcinogenic in the traditional sense, they do not break DNA and do not cause direct mutations. Yet, taken together, their mixtures appear capable of destabilizing the regulatory circuits that keep the identity of liver cells stable.
The researchers observed that chronic exposure to pesticide mixtures alters some key proteins that act as “conductors” inside each cell: their job is to establish which genes should be active and which should not, thus keeping each cell faithful to its function. When these proteins are disturbed, the cell does not die or mutate but loses stability. It enters a sort of gray zone, suspended between health and disease, in which it becomes much more vulnerable to further aggression: an infection, a metabolic factor, another environmental agent. And it is at that point that tumor transformation can occur.
The most vulnerable communities bear the greatest burden
The study also highlights profound environmental injustice. The areas at highest risk coincide with rural areas where agricultural pressure, deforestation and economic marginalization are concentrated. The Andean-Amazonian indigenous communities, already historically disadvantaged in access to health services, are exposed to significantly higher levels of pesticides than urban populations, on average to twelve different substances at the same time, detected in high concentrations in biological samples.
The researchers also highlight a potentially aggravating climate-related effect: during El Niño events, pesticide use and environmental transport dynamics change, locally increasing the risk of exposure. With global warming making these phenomena more frequent and intense, the problem could worsen further.
The limitations of the study
The authors of the study are clear in recognizing the limitations of their work: individual exposures were not directly measured, and the influence of other factors cannot be completely ruled out. However, the convergence between environmental, geographic and molecular data builds a picture of biological plausibility that is difficult to ignore.
What emerges is a powerful and transferable tool: a method to map, on a national scale and with high resolution, the oncological risk associated with environmental exposure to pesticide mixtures. A model that could also be applied in other countries with similar characteristics, and which offers health authorities and political decision-makers concrete data on which to build targeted interventions.
Because perhaps the most important lesson of this study is that the danger does not come from a single substance, classified and regulated, but from the combined and chronic effect of mixtures of compounds that, individually, no one had ever considered dangerous enough to ban.
