A preclinical study shows that saturated fat in the diet stimulates prostate cancer cells and may contribute to the formation of incurable metastases.
With an estimated 71,000 new cases per year in France, prostate cancer is the most common cancer in men. More than one in nine men will declare prostate cancer during their lifetime, but rarely before the age of 50 (average age of diagnosis: 71 years).
Fortunately, these cancers generally evolve very slowly and do not represent a major cause of short-term mortality. In other words, even after a diagnosis of prostate cancer, men are more likely to die from other chronic diseases associated with aging (cardiovascular disease, diabetes) than from this cancer.
When benign prostate cancer becomes metastatic
However, the situation is much less rosy when prostate cancer becomes aggressive and forms metastases. In these patients, the current therapeutic resources do not make it possible to counter the progression of the cancer and the disease is invariably fatal.
The incidence of metastatic prostate cancer is much higher in Western countries than in Asian countries, suggesting that certain lifestyle factors contribute to the aggressiveness of prostate cancer. Among these, several observations have suggested that the Western diet, characterized by a high intake of processed foods high in saturated fat (as in fast food and processed meals) could represent one of these factors.
For example, the incidence of this cancer is multiplied by 20 when the Japanese migrate from Japan to the West, with the drastic change in lifestyle and diet associated with this migration.
Prostate cancer cells produce saturated fat
This hypothesis has just been supported by the results of a preclinical study carried out by a group of scientists from Harvard University. By comparing the genetic profile of localized (non-invasive) prostate cancer samples to that from invasive metastatic cancers, they first observed that the majority of metastases had lost two genes known to prevent tumor growth, or PTEN and PML. These genetic losses are probably crucial for the progression of prostate cancer into metastases, because the analysis of prostate tissue taken from patients shows a close correlation between the absence of these two genes and deaths caused by prostate metastases.
An unexpected consequence of the loss of these two genes is a sharp increase in fat production by cancer cells. The research group has in fact observed that prostate cancer cells lacking PTEN and PML are characterized by hyperactivation of lipid metabolism, with in particular a significant increase in the production of saturated fat. These fats are involved in the progression of prostate cancer, because the addition of a lipid synthesis inhibitor (fatostatin) drastically reduces the formation of metastases in preclinical models.
Saturated fat triggers the formation of metastases
This participation of saturated fats in the progression of prostate cancer into metastasis does not seem to be limited to the fats produced by the cancer cells themselves. Using transgenic mice in which the PTEN and PML genes had been knocked out, the study authors noted that prostate tumors formed few metastases when the animals ate their usual low-fat, plant-based food. .
On the other hand, when lard (a rich source of saturated fat) is added to this diet, they observed that cancer cells accumulated large amounts of saturated fat and that this accumulation was correlated with a marked increase in the number of metastases.
Low saturated fat diet recommended
In other words, the presence of large amounts of saturated fat in the diet acts as a kind of “trigger” that promotes the aggressiveness of prostate cancer cells and induces the formation of metastases.
For men with minimally invasive prostate cancer, a diet low in saturated fat, for example by limiting the consumption of processed industrial foods, could therefore help prevent the development of cancer into metastases and thus avoid dying prematurely from this disease.
Epstein MM et al. Temporal trends in cause of death among Swedish and US men with prostate cancer. J. Natl Cancer Inst. 2012; 104: 1335-1342.
Chen M et al. An aberrant SRE-BP-dependent lipogenic program promotes metastatic prostate cancer. Nature Genet. 2018; 50: 206-218.