Oily fish and cancer

Omega-3 acids in fish appear to be protective against prostate cancer

29 mar 2009--“Oily fish can stop cancer,” reported the Daily Express. It said that a study has found that a three-ounce portion of oily fish just once a week could help men to survive prostate cancer. The newspaper added that prostate cancer can be reduced by almost 60% with a higher intake of omega-3, the fatty acids found in oily fish. The researchers claimed that omega-3 reverses the effects of an inherited gene that can lead to the development of an aggressive form of the disease.

The study looked at fish and fatty acids in the diets of men with and without aggressive prostate cancer. It found that healthy men had a higher intake of omega-3 fatty acids, and interpreted this to mean that omega-3 has a protective effect against cancer. It also found that men with a particular gene variation that codes for the COX-2 enzyme had increased risk of prostate cancer, and this risk fell with higher omega-3 consumption.

This research cannot prove that oily fish protects men from prostate cancer because diet was assessed when cancer was already established. However, it does further our understanding of possible interactions between dietary factors and genetics in the development of cancer.

Where did the story come from?

The risk factors for prostate cancer are not definite but are thought to include:

• increased age
• family history
• weight
• ethnicity (Afro-Caribbeans being at higher risk)
• diet is also possibly involved

The research was carried out by Vincent Fradet and colleagues from the departments of Urology, Epidemiology and Biostatistics and the Institute for Human Genetics, University of California, San Francisco, and the Department of Preventive Medicine, University of Southern California. The study was funded by grants from the National Institute of Health and a Laval University McLaughlin dean’s grant. The study was published in the peer-reviewed medical journal Clinical Cancer Research.

What kind of scientific study was this?

This case-control study investigated whether omega-3 (LC n-3) polyunsaturated fatty acids (PUFA) can reduce the risk of prostate cancer. The researchers aimed to test the theory that any potential effect of omega-3 fatty acids is modified by a genetic variation in cyclooxygenase-2 (COX-2), an enzyme that is involved in the breakdown of fatty acids, and which also has a role in inflammatory processes in the body.

The researchers recruited 466 men with aggressive prostate cancer from major hospitals in Ohio. The tumours were confirmed as aggressive through several tests, including stage, Gleason score (based on histological findings) and prostate-specific antigen (PSA) levels. All men with prostate cancer (cases) were recruited within a short time of diagnosis, typically 4.7 months. A control group was identified from men undergoing standard annual check-ups at the same hospitals. These 478 men had no cancer diagnosis and were matched to the cases in terms of age and ethnicity.

All the men were given a validated food frequency questionnaire. The researchers also examined the men’s DNA, and looked at variations in the genetic sequence coding for the COX-2 enzyme.

Analysis involved determining the link between dietary intake of fish, omega-3 and omega-6 PUFAs and aggressive forms of prostate cancer.

Types of fish included:

• Boiled or baked dark fish, e.g. salmon, mackerel and bluefish.
• Boiled or baked white fish, e.g. sole, halibut, snapper and cod.
• Unfried shellfish, e.g. shrimp, lobster and oysters.
• Tuna (canned).
• Fried fish and shellfish.

Fish intakes were classed as ‘never’, ‘one to three times per month’, or ‘one or more times per week’. In their statistical analyses, the researchers looked at associations between the genetic codes for COX-2 and aggressive prostate cancer. They also took into account the possible confounding effects of smoking, weight, family history of prostate cancer, and prior history of PSA screening.

What were the results of the study?

The average age of both cases and controls was 65 years, and 83% were of Caucasian origin. The average PSA at the time of cancer diagnosis was 13.4 ng/mL, and the majority of cases had a Gleason score of seven or greater. The cases had a more frequent family history of prostate cancer and previous history of PSA testing compared to the controls.

The cases had higher total calorie intake and higher average intake of fat, and a type of omega-6 fatty acid (linoleic acid). The controls had a significantly higher average intake of dark fish, shellfish and the omega-3 fatty acids.

The risk of prostate cancer with the highest quartile of omega-3 intake was significantly reduced compared to the lowest quartile of intake (odds ratio 0.37, 95% confidence interval 0.25 to 0.54). A particular sequence variation in the gene coding for COX-2 (SNP rs4648310) significantly affected the association between prostate cancer and omega-3 intake. Men who had this particular genetic sequence along with a low omega-3 intake had a 5.5 times increased risk of disease. Increased intake of omega-3 fatty acids reversed this risk in these men.

What interpretations did the researchers draw from these results?

The researchers conclude that long-chain omega-3 polyunsaturated fatty acids in the diet appear to be protective against aggressive prostate cancer, and this effect is modified by the genetic variation COX-2 SNP rs4648310. They say that their findings support the theory that omega-3 may have an impact on prostate inflammation and cancer development through interaction with the COX-2 enzyme.

What does the NHS Knowledge Service make of this study?

This is valuable research, which furthers understanding of the possible interaction between dietary factors and the influence of genetics in the development of cancer. However, it does have some limitations. The main one is that despite the demonstrated link, it cannot prove causation because diet was assessed when cancer was already established. Diet at that time may not reflect life-long patterns, and although a validated questionnaire was used, there is always the possibility that the participants had recall bias, and gave inaccurate estimates of the frequency and quantity of the foods they ate.

Additionally, the study findings apply to a specific group: all the cases were men with aggressive prostate cancer detected through PSA screening. Attendance for screening, as the researchers say, may reflect more health-conscious behaviour that could also have an effect on other risk factors. Different findings might be found from other stages of prostate cancer and wider population groups.

Using the results of this study, no assumptions should be made about the effects of omega-3 fatty acids on other cancers, or on the prognosis or development of prostate cancer (this study did not look at cancer treatment, response or survival).