Oncogenes genes play a role in cancer initiation and progression, and MYC is one of these. “In this paper, we showed that by mimicking a MYC overexpression, saturated fat intake makes prostate cancer worse,” says Dr. Labbé, who started this study at the Dana-Farber Cancer Institute in the United States.
“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 Dr. Labbé, assistant professor in the Department of Surgery, Division of Urology at McGill University.
Analyzation of answers to validated food frequency questionnaires obtained from the Health Professionals Follow Up Study and the Physicians Health Study cohorts enabled the team to stratify prostate cancer patients based on their fat intake after identifying and examining high fat diet vs low fat diet and types of fat the patients were consuming, either saturated, monounsaturated, or polyunsaturated fat.
Integration of dietary and gene expression data from 319 patients revealed that animal fat and specifically saturated fat consumption mimicked a MYC overexpression; findings were validated in vivo using a murine prostate cancer model.
Patients with the highest levels of saturated fat intake MYC signature were found to be 4 times more likely to die from prostate cancer independently of age or year of diagnosis. The association remained significant even after adjusting for cancer Gleason grade, which is an indicator of the aggressiveness of the disease.
Fat consumption could be linked to an increase in body fat and obesity, and since obesity is a risk factor associated with prostate cancer the Body Mass Index was used to make sure it was only saturated fat intake and not obesity that promoted progression to metastatic and lethal disease states.
“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,” says Dr. Labbé. “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.”
“In a prostate cancer patient, the prostate contains both tumour and normal tissue,” explains Dr. Labbé. “We showed that saturated fat intake only affects the transcriptional program in the tumour 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.”
“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 Dr. 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.”
