Saturated fat intake leads to cellular reprogramming associated with prostate cancer progression and lethality, according to new research.
These findings could help in identifying patients at higher risk of a more aggressive, lethal disease. In addition, they suggest that dietary intervention involving the reduction of animal fat, and specifically saturated fat consumption in men with early-stage prostate cancer, could possibly diminish or delay the risk of disease progression.
Some genes—called oncogenes—play a role in cancer initiation and progression. MYC is one of those.
“In this paper, we showed that by mimicking a MYC overexpression, saturated fat intake makes prostate cancer worse,” says David P. Labbé, assistant professor in the surgery department of the urology division at McGill University.
“MYC overexpression profoundly rewires cellular programs and bolsters a distinctive transcriptional signature. MYC is a key factor in tumorigenesis, i.e., it induces malignant properties in normal cells and fuels the growth of cancer cells,” adds Labbé, who is also a scientist at the Research Institute of the McGill University Health Centre.
Higher prostate cancer death risk
Based on answers to validated food frequency questionnaires obtained from the Health Professionals Follow-Up Study and the Physician Health Study cohorts, researchers stratified prostate cancer patients based on their fat intake—high-fat diet vs. low-fat diet—and the type of fat they eat—either saturated, monounsaturated, or polyunsaturated fat.
After integrating dietary and gene expression data from 319 patients, the researchers discovered that animal fat and specifically saturated fat consumption mimicked a MYC overexpression. They validated their findings in vivo using a murine prostate cancer model.
Strikingly, patients who had the highest level of the saturated fat intake (SFI) MYC signature were four times more likely to die from prostate cancer, compared to patients with the lowest level, independently of the patient’s age or year at diagnosis.
Even after adjusting the results for cancer Gleason grade—an indicator of the aggressiveness of the disease—this association remained significant.
Since fat consumption may link to an increase in body fat and obesity, and since obesity is also a risk factor associated with prostate cancer, Labbé used body mass index (BMI) to make sure that it was only saturated fat intake—and not obesity—that promoted the progression to a metastatic and lethal disease.
“Even after removing obesity from the equation, patients with high levels of the SFI-MYC signature are still three times more likely to die of prostate cancer,” Labbé says. “Epidemiological studies have previously reported that saturated fat intake is associated with prostate cancer progression. Our study provides a mechanistic underpinning to this link and a basis to develop clinical tools aimed at reducing the consumption of saturated fat and increasing the odds of surviving.”
Dietary interventions may help
The study also shows that for saturated fat to induce MYC reprogramming, the tissue needs transforming.
“In a prostate cancer patient, the prostate contains both tumor and normal tissue,” Labbé says. “We showed that saturated fat intake only affects the transcriptional program in the tumor tissue.”
“Altogether, our findings suggest that a substantial subset of prostate cancer patients, including some without MYC amplification, may benefit from epigenetic therapies targeting MYC transcriptional activity or from dietary interventions targeting metabolic addictions regulated by MYC.”
Knowing the dietary pattern of a patient or his level of physical activity, clinicians could eventually suggest some specific intervention to decrease the likelihood of progression to a lethal disease. But in order to do that, researchers need to do more work.
“The impact of diet on cancer development has been first established more than 100 years ago. However, lifestyle-related data is only sparsely collected among patients, thereby limiting our capacity to define the molecular link between lifestyle factors and cancer initiation, progression, and lethality,” says Labbé.
“We will start soon here at the RI-MUHC to gather dietary and physical activity and assess body fatness information from patients undergoing screening tests for different cancers. And with that data, combined with research in the laboratory, we hope to be able to build personalized interventions for patients who are more at risk of having their cancer progress rapidly, and to ultimately improve outcomes.”