Image from www.medpagetoday.com

Published: Nov 20, 2013 | Updated: Nov 20, 2013
By Charles Bankhead, Staff Writer, MedPage Today

Full Story:  http://www.medpagetoday.com/HematologyOncology/ProstateCancer/43042

Prostate cancer patients who consumed a low-fat, high fish oil diet had significantly less tissue inflammation and proliferation than patients who ate a typical Western diet, investigators reported.

Levels of omega-3 fatty acids increased significantly, whereas relatively pro-inflammatory omega-6 decreased, as did the pro-inflammatory eicosanoid 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and the cell cycle progression (CCP) score.

The decline in 15(S)-HETE correlated with changes in the proliferation marker Ki67, but not with the CCP score (a marker of cancer aggressiveness). Levels of pro-inflammatory leukotriene B4 (LTB4) correlated with CCP score but not with Ki67, as reported online in Cancer Prevention Research.

“We also demonstrated that a low-fat fish oil intervention reduced expression of genes involved in cell cycle progression,”William Aronson, MD, of the University of California Los Angeles, and co-authors concluded. “The CCP score has been previously shown to be an independent predictor of recurrence after radical prostatectomy and of prostate cancer death, and, more recently, a predictor of biochemical recurrence for patients treated with external beam radiation therapy as their primary therapy.

“The finding that CCP score was lower in the low-fat fish oil versus Western diet group provides strong support for longer-term, prospective randomized trials evaluating a low-fat fish oil diet in men with prostate cancer.”

A 100-patient randomized trial will begin next year. Investigators will compare a low-fat fish oil diet to a conventional diet in men with low-risk prostate cancer who have opted for active surveillance instead of definitive treatment, Aronson said in a statement.

Laboratory studies have shown that reducing intake of omega-6 fatty acids (derived from corn oil) and increasing consumption of omega 3-rich fish oil delayed the development and progression of prostate cancer. Epidemiologic and observational studies have yielded mixed results, Aronson and colleagues noted in their background information.

The ratio of omega-6 to omega-3 fatty acids in adipose tissue and blood reflect dietary fatty acid consumption. The fatty acids are converted to metabolically active eicosanoids that reflect their source.

Eicosanoids produced from omega-6 fatty acids (such as thromboxanes, HETEs, and leukotrienes) have pro-inflammatory properties, whereas those originating from omega-3 are less inflammatory or anti-inflammatory.

LBT4 and 15(S)-HETE bind to a receptor (BLT2) that is a mediator of androgen-receptor expression in androgen-dependent prostate cancer cell lines. LBT4 also binds to BLT1, which has been shown to have proliferative effects in ovarian, colon, and pancreatic cancer, the authors continued.

Aronson and colleagues previously reported lower levels of the proliferation marker Ki67 in radical prostatectomy specimens from men who consumed a low-fat fish oil diet (intervention) as compared with specimens from men who consumed a Western diet. The intervention was associated with a lower ratio of omega-6 to omega-3 fatty acids in erythrocytes and in benign and malignant prostate tissue.

Continuing their analysis of data from the earlier trial, investigators compared levels of LTB4 and 15(S)-HETE and the cell cycle progression score in 48 prostate cancer patients assigned to the two dietary groups.

The analysis showed a decline in mean 15(S)-HETE levels of 7.2% in the fish oil group versus a 24.7% rise in the control group (P=0.02 between groups), a significant decline in levels of LTB4 in the fish oil group (P=0.036) but not the control group, a significant decline in 15(S)-HETE within the intervention group (P=0.039), and a significantly lower CCP in the intervention versus control group (P=0.03).

The researchers also found a positive correlation between lower CCP score and lower blood levels of LBT4.

“Given this finding, we went on to explore how the LTB4 might potentially affect prostate cancer cells and discovered a completely novel finding that one of the receptors for LTB4 (BLT1) is found on the surface of prostate cancer cells,” said Aronson.

Offering a low-fat fish oil diet to prostate cancer patients in active surveillance is intriguing but goes beyond the scope of this study, said Stephen Freedland, MD, of Duke University, who has evaluated the same test used by Aronson and colleagues to study CCP.

“It certainly requires validation in a study where [the effect in active surveillance] is the primary outcome,” Freedland told MedPage Today. “If shown to really be the case, and given that cell cycle progression does correlate with cancer progression, it would be reasonable to think that this approach would slow cancer progression and be a great option for men on active surveillance.”