Link Between Omega-3 Fatty Acids and Increased Prostate Cancer Risk Confirmed

Consumption of fatty fish and fish-oil supplements linked to 71 percent higher risk: 

Alan Kristal

Senior author Alan Kristal, Dr.P.H., is a member of the Public Health Sciences Division at Fred Hutch.

A second large, prospective study by scientists at Fred Hutchinson Cancer Research Center has confirmed the link between high blood concentrations of omega-3 fatty acids and an increased risk of prostate cancer.

Published in the online edition of the Journal of the National Cancer Institute, the latest findings indicate that high concentrations of EPA, DPA and DHA – the three anti-inflammatory and metabolically related fatty acids derived from fatty fish and fish-oil supplements – are associated with a 71 percent increased risk of high-grade prostate cancer. The study also found a 44 percent increase in the risk of low-grade prostate cancer and an overall 43 percent increase in risk for all prostate cancers.

The increase in risk for high-grade prostate cancer is important because those tumors are more likely to be fatal.

The findings confirm a 2011 study published by the same Fred Hutch scientific team that reported a similar link between high blood concentrations of DHA and a more than doubling of the risk for developing high-grade prostate cancer. The latest study also confirms results from a large European study.

“The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis and recommendations to increase long-chain omega-3 fatty acid intake, in particular through supplementation, should consider its potential risks,” the authors wrote.

“We’ve shown once again that use of nutritional supplements may be harmful,” said Alan Kristal, Dr.P.H., the paper’s senior author and member of the Fred Hutch Public Health Sciences Division. Kristal also noted a recent analysis published in the Journal of the American Medical Association that questioned the benefit of omega-3 supplementation for cardiovascular diseases. The analysis, which combined the data from 20 studies, found no reduction in all-cause mortality, heart attacks or strokes.

Theodore Brasky

Corresponding author Theodore Brasky, Ph.D., a research assistant professor at The Ohio State University Comprehensive Cancer Center, was a postdoctoral trainee at Fred Hutch when the research was conducted.

“What’s important is that we have been able to replicate our findings from 2011 and we have confirmed that marine omega-3 fatty acids play a role in prostate cancer occurrence,” said corresponding author Theodore Brasky, Ph.D., a research assistant professor at The Ohio State University Comprehensive Cancer Center who was a postdoctoral trainee at Fred Hutch when the research was conducted. “It’s important to note, however, that these results do not address the question of whether omega-3’s play a detrimental role in prostate cancer prognosis,” he said.

Kristal said the findings in both Fred Hutch studies were surprising because omega-3 fatty acids are believed to have a host of positive health effects based on their anti-inflammatory properties. Inflammation plays a role in the development and growth of many cancers.

It is unclear from this study why high levels of omega-3 fatty acids would increase prostate cancer risk, according to the authors, however the replication of this finding in two large studies indicates the need for further research into possible mechanisms. One potentially harmful effect of omega-3 fatty acids is their conversion into compounds that can cause damage to cells and DNA, and their role in immunosuppression. Whether these effects impact cancer risk is not known.

The difference in blood concentrations of omega-3 fatty acids between the lowest and highest risk groups was about 2.5 percentage points  (3.2 percent vs. 5.7 percent), which is somewhat larger than the effect of eating salmon twice a week, Kristal said.

The current study analyzed data and specimens collected from men who participated in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a large randomized, placebo-controlled trial to test whether selenium and vitamin E, either alone or combined, reduced prostate cancer risk. That study showed no benefit from selenium intake and an increase in prostate cancers in men who took vitamin E.

The group included in this analysis consisted of 834 men who had been diagnosed with incident, primary prostate cancers (156 were high-grade cancer) along with a comparison group of 1,393 men selected randomly from the 35,500 participants in SELECT.

The National Cancer Institute and the National Center for Complementary and Alternative Medicine funded the research.

Also participating in the study were additional Fred Hutch scientists and researchers from the University of Texas, University of California, University of Washington, National Cancer Institute and the Cleveland Clinic.

 Fish oil linked to prostate cancer. NBC’s Dr. Nancy Snyderman reports.

 

References

Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL Jr, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR. Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial. J Natl Cancer Inst 2013 Jul 10. [Epub ahead of print]

Brasky TM, Till C, White E, Neuhouser ML, Song X, Goodman P, Thompson IM, King IB, Albanes D, Kristal AR. Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol 2011; 173: 1429-39.

Council for Responsible Nutrition. CRN Says New Study on Omega-3 Conclusions Are Overblown. Press Release, July 11, 2013.

 

Beehive Extract Shows Potential as Prostate Cancer Treatment

Proteomics reveals how ancient remedy slows prostate tumor cell proliferation: 

An over-the-counter natural remedy derived from honeybee hives arrests the growth of prostate cancer cells and tumors in mice, according to a new paper from researchers at the University of Chicago Medicine.

Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells.

In a paper published in Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells’ system for detecting sources of nutrition.

“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” said Richard B. Jones, PhD, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. “So it doesn’t kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”

Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.

“It’s only recently that people have examined the mechanism by which some of these herbal remedies work,” Jones said. “Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you’re left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease.”

To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.

CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.

To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the “micro-western array.” Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.

Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth – experiments that would have been prohibitively expensive without the new technique.

“What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that’s never been possible before,” Jones said. “It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies.”

The micro-western array results allowed researchers to quickly build a new model of CAPE’s cellular effects, significantly expanding on previous work that studied the compound’s mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.

“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there’s nutrition available,” Jones said. “They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition.”

The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.

“A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy,” Jones said. “Now we’ll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”

 

Reference

Chuu CP, Lin HP, Ciaccio MF, Kokontis JM, Hause RJ, Hiipakka RA, Liao S, Jones RB. Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks. Cancer Prev Res 2012; 5: 788-797.

 

Vitamin E in Diet Protects Against Many Cancers

Researchers find form commonly used in supplements has no such benefit. 

Vitamin E in vegetable oils and nuts prevents cancer, according to research done at Rutgers University and the Cancer Institute of New Jersey.

Next time you need to choose between vegetable oil and margarine in that favorite recipe, think about your health and reach for the oil.

While the question of whether vitamin E prevents or promotes cancer has been widely debated in scientific journals and in the news media, scientists at the Center for Cancer Prevention Research, at Rutgers Mario School of Pharmacy, and the Cancer Institute of New Jersey, believe that two forms of vitamin E – gamma and delta-tocopherols – found in soybean, canola and corn oils as well as nuts do prevent colon, lung, breast and prostate cancers.

“There are studies suggesting that vitamin E actually increases the risk of cancer and decreases bone density,” says Chung S. Yang, director of the center. “Our message is that the vitamin E form of gamma-tocopherols, the most abundant form of vitamin E in the American diet, and delta-tocopherols, also found in vegetable oils, are beneficial in preventing cancers while the form of vitamin E, alpha- tocopherol, the most commonly used in vitamin E supplements, has no such benefit.”

Director of the Center for Cancer Prevention Research at Rutgers Ernest Mario School of Pharmacy

Yang and colleagues, Nanjoo Suh and Ah-Ng Tony Kong, summarized their findings recently in Cancer Prevention Research, a journal of the American Association for Cancer Research. In a Commentary, Does Vitamin E Prevent or Promote Cancer? the Rutgers scientists discuss animal studies done at Rutgers as well as human epidemiological studies that have examined the connection between vitamin E and cancer.

Yang says Rutgers scientists conducting animal studies for colon, lung, breast and prostate cancer found that the forms of vitamin E in vegetable oils, gamma and delta-tocopherols, prevent cancer formation and growth in animal models.

“When animals are exposed to cancer-causing substances, the group that was fed these tocopherols in their diet had fewer and smaller tumors,” Yang says. “When cancer cells were injected into mice these tocopherols also slowed down the development of tumors.”

In researching colon cancer, Yang pointed to another recently published paper in Cancer Prevention Research indicating that the delta-tocopherol form of vitamin E was more effective than other forms of vitamin E in suppressing the development of colon cancer in rats.

This is good news for cancer research. Recently, in one of the largest prostate cancer clinical trials in the United States and Canada, scientists found that the most commonly used form of vitamin E supplements, alpha-tocopherol, not only did not prevent prostate cancer, but its use significantly increased the risk of this disease among healthy men.

This is why, Yang says, it is important to distinguish between the different forms of vitamin E and conduct more research on its cancer preventive and other biological effects.

“For people who think that they need to take vitamin E supplements,” Yang says, “taking a mixture of vitamin E that resembles what is in our diet would be the most prudent supplement to take.”

 

Reference

Yang CS, Suh N, Kong AN. Does Vitamin E Prevent or Promote Cancer? Cancer Prev Res (Phila). 2012 Apr 16. [Epub ahead of print]