Salmon, Prostate Cancer and a COX-2 gene variant

Salmon is a super-food even compared to other oily fish like mackerel and herring. According to a study that breaks new ground, salmon’s omega-3 fatty acids are especially protective against prostate cancer for men who have one specific, common variation in a single gene.

Maria Hedelin. Ph.D.
Maria Hedelin PH.D.

Maria Hedelin, a scientist at the Karolinska Institute in Stockholm, Sweden has found evidence that the protective effect of salmon and marine fatty acids apply with extra potency to men with a genetic variation in the COX-2 gene, which is a gene that helps regulate the body's production of inflammatory chemicals called prostaglandins.

High intake of marine fatty acids and oily fish, especially salmon, Hedelin's study found, "is strongly associated" with decreased relative risk of prostate cancer.

Not all fish are as beneficial. This study found that "high intake of lean fish and shellfish is associated with an increased risk of prostate cancer."

Looking at genes as well as food intake, Hedelin discovered that men with a common variant in the COX-2 gene called single nucleotide polymorphism (SNP) (rs5275: +6365 T/C) received significantly more protection from salmon than other men do. Men with this variant SNP, which is present in a large segment of the population, gained a 72% percent reduction in risk of prostate cancer from intake of salmon more than once per week.

Two omega-3 fatty acids that are abundant in fatty fish, EPA and DHA, have well-known anti-inflammatory properties. Evidence suggests that they protect against cardiovascular diseases. Cell tests in the laboratory have shown that omega-3 fatty acids can prevent the development of some cancers.

Hedelin and her team asked 1,500 Swedish men with diagnosed prostate cancer and a thousand men never diagnosed with this disease about their eating habits. The results strongly support the healthiness of marine fatty acids, she says. Overall, men with high fish intake including salmon (more than once a week) showed a 43 per cent less chance of developing prostate cancer than men who never ate fatty fish. This overall reduction was strongly weighted by the potent effect of marine fatty acids on the 60 percent of men carrying the mutated COX-2 gene.

COX-2 gene is involved in inflammation; which has been linked to prostate cancer (and colon cancer) as well as to cardiovascular disease, arthritis and other conditions. Drugs that block COX-2 activity, such as NSAIDs, have been found to reduce progression of prostate cancer.

Hederlin discovered that COX-2 variant SNP status and dietary patterns may affect risk of prostate cancer. Men who ate fatty fish regularly and had the COX-2 (SNP) (rs5275: +6365 T/C) variant, she found, had a 72% lower risk of prostate cancer compared with men carrying the regular ("wild-type") COX-2 gene.

Her findings may affect what to pick up at the supermarket and might well strengthen resistance to fast foods:

  • Mackerel, herring and other fatty fish had no protective effect on risk of prostate cancer unless salmon was eaten too.
  • Men who ate a lot of lean fish (like cod and pollock) and/or shellfish had a higher risk of prostate cancer.
salmon, photo by quil
Fresh salmon

This finding about lean fish is quite a shocker. Although fish such as cod and pollock lack fatty acids, they're considered nutritious and "heart-healthy." Why would eating lean fish raise the risk of prostate cancer? Hedelin suggests tow points -- pollutants in lean fish and preparation and cooking methods that combine lean fish and shellfish with an overload of omega-6 fatty acids.

"Seafood from open seas contains varying levels of contaminants (e.g. methyl-mercury, organochlorine compunds, polychlorinated biphenyls and dioxins)," she writes, "whereas salmon-type fish consumed in Sweden is generally farm-raised and contains a lower level of contaminants. There is, however, no conclusive evidence that these compounds are associated with prostate cancer." Lean fish and shellfish eaten in Sweden, she says, are ocean-caught and more prone to pollution than the farm-raised salmon that is consumed there today.

Yet U.S. evidence suggests that farm-raised salmon are higher in PCB's than salmon caught wild from the ocean.

Other studies have not found associations between lean fish and prostate cancer, Hedelin allows. "Almost all of them ," Hedelin says, "looked at total intake of fish," which might have led to "underestimation of any protective effect of fatty fish.In any case, some evidence of strong protection against prostate cancer from fish consumption has come, from studies "in countries with a high . . . intake of marine fatty acids. . . . "

Fish is certainly one of an array of foods that people mix and match and process and cook according to ethnic and cultural habits and traditions under evolving commercial pressures. Traditionally, Scandinavians eat dried salt cod or "smoked and cured fish How many people today eat fish stew, fish soup or steamed fish? Lean fish like Alaskan pollock (saithe), which according to Wikipedia "is the largest food fish resource in the world," is sold mostly as filleted fish frozen into blocks (hardly appetizing for steaming) or minced and extruded, breaded or battered, for frozen fish fingers. A typical US fast-food "fish" meal features battered fish patties on a bun with a side of French fries followed by an omega-6 and/or saturated fat loaded shake or ice cream.

dill

Hedelin agrees with may previous commentators who hold as she does that "the ratio of omega3/omega-6 fatty acids might be more important than the absolute intake of omega-3 fatty acids." In Western diets, she points out, this ratio "is lower than that in Far Eastern countries, where the incidence of prostate cancer is lower."

Knowing SNP (rs5275: +6365 T/C)" on COX-2 gene protects men who eat a lot of marine fatty acids against prostate cancer won't make much difference to how men plan their diets unless/until genetic testing becomes available to the general public. But this is what Hedelin found, and it accords with some other discoveries about COX-2. Hedelin's team found:

  • Men with the particular variant of the COX-2 gene had a strikingly lower risk of prostate cancer. Those who ate salmon-type fish once a week or oftener had a 72 per cent lower risk than men who never ate fatty fish.
  • Men without this gene variant showed a slight lowering of risk of prostate cancer from a weekly serving; but only those who typically ate salmon 5 or more times a week showed a substantially lowered risk -- though still not as low as that of the super-responders with the genetic protection.

COX-2 controls the outcome when omega-3 fatty acids compete with omega-6 fatty acids for inclusion in hormone-like substances in the body known as prostaglandins. Prostaglandins derived from omega-3 fatty acids are anti-inflammatory and may to some degree counteract the development of cancer. Prostaglandins derived from omega-6 fatty acids have the opposite effect, promoting inflammation and cancer and other inflammatory diseases such as cardiovascular disease, osteoporosis, and autoimmune diseases.

This discovery about the protective version of Cox-2 still leaves Westerners to face up to a gross dietary imbalance. Even people who eat salmon frequently and take omega-3 marine oil supplements may encounter a tsunami of omega-6 fatty acids if they also consume processed and fried foods and snacks made with polyunsaturated vegetable oils, especially safflower, sunflower, soy, and corn oil.

It's been said that human beings evolved "on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1 to 16.7/1" (Simopoulos, below).

Oncologist Charles E. Myers M. D., who has devoted two issues of his Prostate Forum Newsletter to omega fatty acids, says that for men with prostate cancer, consuming foods or supplements high in omega-6 fatty acids is like throwing fat a blazing fire. Among foods and supplements that Dr. Meyers is asked about constantly are flaxseed and flaxseed oil. He recommends against both. Scandinavians eat flaxseed in rye bread. Flax is high in
lignans and in alpha-linolenic acid (ALA), is a polyunsaturated omega-3 fatty acid.
Hedein's team found that the omega-3 fatty acid xontent of flax is not protective. "In accordance with other studies," she writes, "we found that the omega-3 fatty acid alpha-linolenic acid was associated with an increased risk of prostate cancer."

The sensitivity of the prostate to marine omega-3 oil intake and to variants in the COX-2 gene is, presumably, tied in with the fact that prostaglandin E2, an eicosanoid product of COX-2 acting on arachidonic acid, is produced at 10 times the rate in prostate cancer tissue as in healthy tissue. The importance of COX-2 activity in this disease, the Swedish scientists point out, was further underscored by the discovery that genetic variation in the COX-2 gene affects the risk of prostate cancer

Related news stories

wild salmon jumps upstream
Wild salmon returning home to spawn

Farmed Salmon Show High Levels of Cancer-Causing PCBs "U.S. Adults Eat Enough PCBs From Farmed Salmon to Exceed Allowable Lifetime Cancer Risk 100 Times Over" Aug 2003.

Eating Fatty Fish May Slash Risk Of Prostate Cancer June 2001

Sources and references

Hedelin, Maria Dietary and genetic factors in the etiology of prostate cancer June 9, 2006. Doctoral Thesis. .pdf

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism. Hedelin M, et al, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Int J Cancer. 2007 Jan 15;120(2):398-405.

The importance of the ratio of omega-6/omega-3 essential fatty acids. Simopoulos AP, The Center for Genetics, Nutrition and Health, Washington, DC. Biomed Pharmacother. 2002 Oct;56(8):365-79.

A Prospective Study of Intake of Fish and Marine Fatty Acids and Prostate Cancer Katarina Augustsson . . . and Edward Giovannucci, et al. Harvard School of Public Health ... Karolinska Institet. Cancer Epidemiology Biomarkers & Prevention Vol. 12, 64-67, January 2003

The Prostate Cancer Forum:
Volume 8 Number 6, Omega 3 Fatty Acids, I: Fish or Flax?
Volume 8 Number 7, Omega 3 Fatty Acids, II: Fish or Flax?

Links

How can I get more omega 3 fatty acids in my daily meals? The world's healthiest foods.

Fish, Levels of Mercury and Omega-3 Fatty Acids American Heart Association

Omega-3 and other cancers

Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers Helmut Bartsch et al. German Cancer Research Center (DKFZ), Heidelberg, Germany Carcinogenesis, Vol. 20, No. 12, 2209-2218, December 1999
"a high intake of {omega}-6 PUFAs in cancer of the breast, colon and, possibly, prostate and which indicates that {omega}-3 PUFAs and monounsaturated fatty acids such as oleic acid ({omega}-9) are protective."

COX-2

COX-2 gene promoter haplotypes and prostate cancer risk Ramesh C.K. et al. Carcinogenesis, Vol. 25, No. 6, 961-966, June 2004

3 thoughts on “Salmon, Prostate Cancer and a COX-2 gene variant

  1. staff

    I don''t care much for fish, eccept for tuna. I also like cod, and haddock Is there much omega-3 in this kind of fish? please tell me thank you.

  2. staff

    Salmon contains more omega-3 per serving than tuna and white fish, and tuna may contain more mercury than salmon. If you don't like to eat salmon, perhaps you might consider taking a salmon oil supplement.

  3. osheapj14

    I wouldn't rely on fish for the proper daily intake of omega-3.

    The problem with most salmon (restaurant or supermarket) is that it is farmed & no more healthier than steak. And perhaps less so. You'd be better off with grass-fed beef.

    Avoid almost all farmed fish (tilapia is always farmed, e.g.).

    People think that fish is healthy, but if it is served fried (the only way a lot of people can stomach it), the ratio of omega-6 (from the oil), relative to the omega-3 (from the fish) is so high, that you might as well not bother.

    -Patrick

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