Manipulating Diet May Impact Prostate Cancer Risk, Progression

By David Levy, MD

Increasing data in the literature implicate dietary trends as contributing factors to prostate cancer incidence and aggressiveness.[i],[ii],[iii],[iv]

Elevated dairy and meat intake have been associated with increased incidences and aggressiveness of prostate cancer compared to diets higher in plant-based proteins and fats. [v] Similar findings have been reported for high glycemic-load diets, which are positively associated with an increased incidence of prostate cancer, (odds ratio [OR] 1.26, highest versus lowest quartile). [vi]

While additional factors clearly impact disease behavior, these dietary observations meet statistical significance and warrant further investigation. The data indicate that manipulation of dietary and lifestyle factors may impact prostate cell metabolism and prostate cell behavior characteristics. Cleveland Clinic is involved in dietary intervention efforts in an attempt to affect patients’ prostate cancer risk and progression.

Vitamin D’s role

Specific attributes of the vitamin D pathway gene located on chromosome 12 and circulating vitamin D levels have been correlated with prostate cancer biology. In 2015, data from a cohort of 1,275 prostate cancer patients revealed that individuals with demonstrated active coding of the polymorphisms rs4588-A (p = 0.04) and rs7041-T (p = 0.03) — both specific components of the vitamin D receptor gene — manifested lower circulating levels of 25-hydroxyvitamin D and elevated prostate cancer risk. [vii]

In a separate cohort of 1,289 patients, deficient levels of vitamin D (< 12 ng/dL) correlated with a two-fold increased risk of advanced versus localized prostate cancer, (OR 2.33, 95 percent confidence interval [CI] 1.26-4.28) as well as high-grade versus low-grade disease, (OR 1.78, 95 percent CI 1.15-2.77).[viii]

Similar findings were reported in a study of 667 prostate cancer patients with low circulating vitamin D levels (< 12 ng/mL) correlated with Gleason score > 8 (OR 3.66; 95 percent CI 1.41-9.50; p = 0.008) and clinical T stage > cT2b versus < cT2a, (OR 2.42; 95 percent CI 1.14-5.10; p = 0.008).[ix]

Circulating vitamin D levels and vitamin D androgen receptor interaction appear to have a role in prostate cancer cell biology.

The impact of polyunsaturated fats

Polyunsaturated fatty acids (PUFAs) may also impact aspects of prostate cancer biology.[x] There are data that correlate Western dietary fat consumption with breast, colon, pancreatic and prostate cancer and that demonstrate a relative protective effect of omega-3 PUFAs against these cancers.[xi],[xii], [xiii], [xiv] A potential role of fatty acids in the prostate cancer bone metastasis pathway has been suggested in published studies.[xv]

The ratio of n-6/n-3 PUFAs may also be important.[xvi] The typical Western diet ratio is greater than 10:1, while the typical Japanese diet has a ratio of 4:1. [xvii] Interestingly, the incidence of prostate cancer in Japan is much lower than most Western countries. In a case-control study involving 79 prostate cancer patients, higher dietary ratios of n-6/n-3 were significantly associated with increased risk of high-grade cancer (OR 3.55; 95 percent CI 1.18-10.69; p trend = 0.03) in all men, as well as positively correlated with overall risk of prostate cancer among white men.[xviii]

In a recent phase II prospective randomized controlled trial, patients received either a traditional Western diet or a low-fat diet supplemented with 5 grams of fish oil daily for 4-6 weeks prior to radical prostatectomy. At the time of prostatectomy, specimen analysis revealed that individuals on the low-fat/fish oil diet had a 32.2 percent decrease in cancer cell proliferation as measured by Ki-67 (p = 0.026) as well as decreased n-6/n-3 ratios in both the benign and malignant prostate tissue (p < 0.001 and p < 0.001, respectively).[xix]

A follow-up study by Aronson, et al., revealed that a low-fat/fish oil diet led to decreased cell cycle progression scores (p = 0.03) as well as decreased serum levels of the pro-inflammatory n-6 metabolite 15(S)-HETE compared to the Western-diet (p = 0.02).[xx] These findings lend support to potential detrimental effects of n-6 PUFA on prostate cancer proliferation and a potential beneficial effect of low n-6/n-3 ratios.

Genetic changes

Finally, studies have been published that demonstrate changes in prostate cell cycle progression and down-regulation of genetic transcripts after dietary manipulation and administration of supplements.[xxi],[xxii]

In a cohort of patients with untreated localized disease, genetic assessment of biopsy cores at the time of entrance into an intensive dietary and behavioral modification program was conducted. At 12 weeks into the program, repeat prostate biopsy and genetic assessment revealed 48 up-regulated and 453 down-regulated gene transcripts in normal prostate tissue in the men undergoing the intervention compared to the controls. Specifically, protein metabolism and modification pathways, intracellular protein traffic (31 gene transcripts) and protein phosphorylation were all significantly down-regulated (p < 0.05). RAS family oncogenes (RAN, RAB14 and RaB8A) were also down-regulated.

Dietary interventions

Based upon these data, we anticipate being able to impact prostate cell biology by means of an intensive dietary manipulation and supplement program for men with known prostate cancer.

Cleveland Clinic’s Department of Urology recently established a multimodality Prostate Nutrition Clinic that addresses the effect of patient dietary habits on prostate pathology. The clinic, staffed by physicians, nurse practitioners and nutritionists, offers a comprehensive analysis of dietary habits known to be factors in prostate disease as well as an assessment of relevant laboratory data.

This information, coupled with a standard medical assessment and physical exam, allows us to formulate a dietary plan and schedule regular follow-up visits to monitor patients’ progress.

The clinic’s goal is to form a partnership with each patient to maximize health and minimize the risk of systemic disease. Prospective patients include:

• Men with no history of prostate cancer but who have first-degree relatives with the disease
• Patients on active surveillance who hope to alter their disease course
• Patients who have been diagnosed with prostate cancer but have not begun therapy of curative intent
• Prostate cancer patients who have failed conventional treatment

Genetic analysis of prostate tissue from some of the prostate cancer participants in the dietary/ supplement program will be conducted in collaboration with Cleveland Clinic’s Center for Functional Medicine to identify the specific impact that dietary manipulation and supplements have on prostate cell biology.

Dr. Levy is a staff member of Cleveland Clinic Glickman Urological & Kidney Institute’s Department of Urology, Clinical Associate Professor of Surgery at Cleveland Clinic Lerner College of Medicine, and Chief of Urology at Euclid Hospital.