A fat-laden diet and high calcium consumption are both well-known suspected risk factors for prostate cancer. However, new findings from the Fred Hutchinson Cancer Research Center suggest that fat and calcium themselves may not cause prostate cancer, as previously thought, but instead may fuel its progression from localized to advanced disease.

While high intake of dietary fat and calcium is associated with an increased risk of clinically significant, advanced prostate cancer, it has no apparent impact on risk of early-stage disease, according to findings by Alan Kristal, Dr.P.H., and colleagues in Fred Hutchinson's Public Health Sciences Division.

Results of this population-based, case-control study appear today in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research. The National Cancer Institute and Fred Hutchinson funded the research.

"Our findings clearly show decreased risk for late-stage disease in men with diets that are low in fat and moderate in calcium, perhaps because these diets slow progression of prostate cancer into more aggressive disease. For men diagnosed with early-stage prostate cancer, this finding could be important because it suggests that moderating fat and calcium consumption may reduce the risk of cancer recurrence following treatment," said Kristal, a member of Fred Hutchinson's Cancer Prevention Research Program.

This study looked at the associations of total calorie, fat, calcium and vitamin D intake on prostate-cancer risk among 1,200 Seattle-area men ages 40 to 64; more than 60 percent of the participants were under age 60. Half of the men had been recently diagnosed with prostate cancer and the other half were healthy, randomly selected Puget Sound-area residents who served as a comparison group. The men were interviewed about their dietary habits three to five years prior to diagnosis (or an equivalent time frame among the control group). They also completed a detailed dietary questionnaire that asked how much and how often they consumed certain foods and dietary supplements.

While previous studies have examined similar dietary factors on overall prostate-cancer risk, few studies have looked specifically at risk comparing early with advanced disease.

While there is no effective treatment for advanced prostate cancer, localized disease can be treated with either prostatectomy or radiation therapy. While almost all men diagnosed with early-stage prostate cancer survive for more than five years, only 34 percent of men diagnosed after the disease has spread to distant organs are alive after five years, according to the American Cancer Society.

"As more and more men are diagnosed with early stage disease due to the widespread use of the PSA (prostate-specific antigen) screening test, it becomes increasingly important to consider how dietary or lifestyle changes could decrease their risk of cancer recurrence," said Kristal, also an associate professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

Kristal and colleagues found that men who ate lower-fat diets, with fat accounting for no more than 30 percent of their daily calorie intake, had half the risk of late-stage cancer than men who consumed more fat. However, there were no associations of fat intake with early-stage disease.

Saturated fats (found in meat and dairy fat) and monounsaturated fats (found in certain oils, such as olive and peanut) were associated with an increased risk of advanced prostate cancer. Polyunsaturated fats (found in certain oils, such as safflower and canola) were not. Consumption of omega-3 fatty acids (found in fatty fish such as salmon and mackerel) also did not have an impact on overall prostate-cancer risk, contrary to experimental studies in cell cultures that have suggested there may be a protective effect.

The U.S. Department of Agriculture's Dietary Guidelines for Americans recommends no more than 30 percent of total daily calories from fat. For example, a person who needs 2,000 calories a day based on their height, weight and activity level would want to aim for no more than 600 calories from fat, or 65 grams (1 gram of fat has 9 calories, compared to only 4 calories in a gram of carbohydrate or protein).

One reason that low-fat diets could reduce the risk of prostate cancer is because they reduce blood levels of circulating male hormones such as testosterone. Growth of the prostate, and perhaps growth of prostate cancer, is fueled by male hormones.

The researchers also found the risk of advanced prostate cancer was 112 percent higher - more than double - among men who consumed the most calcium (more than 1,200 mg per day, equivalent to four or more glasses of milk) as compared to those who got the least (fewer than 500 mg). It didn't matter whether the calcium came from food or supplements. "For regional/distant disease, there were consistent trends for increased, independent risks from both dietary and supplemental calcium," the researchers wrote.

The mechanism underlying the effect of calcium on prostate-cancer risk isn't clear, although there are relatively consistent findings from previous studies suggesting that dairy products or calcium-supplement intake are associated with risk. Some scientists hypothesize that a high intake of calcium may suppress blood levels of the active form of vitamin D, a hormone that may protect against prostate cancer by preventing the development of cancerous cells.

The only dietary risk factor that appeared to carry equal weight among men with both early and advanced prostate cancer was the amount of total calories consumed, regardless of fat. "Total energy intake was significantly associated with risk for both localized and advanced disease," Kristal said. Men who ingested the most calories each day more than doubled their risk of localized prostate cancer (a 115 percent increased risk) and nearly doubled their risk of advanced prostate cancer (a 96 percent increased risk) compared to men who ate the fewest.

"Our interpretation of these results is that high energy intake increases prostate cancer risk overall, while high dietary fat and calcium intakes increase the risk of more clinically significant, advanced stages of the disease," the researchers wrote. "These results are consistent with general dietary guidelines to moderate consumption of total energy and fat, and they motivate further research to consider the potential benefits and risks of high calcium intake."

One important implication of this research, Kristal said, is that men who have been diagnosed with early-stage prostate cancer may benefit from a diet low in fat and calories. "While there is an increasingly popular message that fat intake is not important for health," he said, "there is no doubt that high-fat diets are associated with high calorie intake and obesity. A low-fat diet may well be important for the thousands of men who are diagnosed each year with early-stage prostate cancer."

Specific recommendations for calcium consumption are more complex, because calcium also helps prevent osteoporosis and colon cancer.

The U.S. Recommended Daily Intake of calcium for men over age 50 is 1,200 mg. While the most well-known dietary sources of calcium include milk, dairy products, salmon and dark, leafy greens, men - particularly those taking calcium supplements - also should be aware of the additional calcium content in fortified foods, from cereals to juices. A small bowl of fortified cereal, for example, can contain up to 1,000 mg of calcium.

"Men diagnosed with early-stage prostate cancer may wish to moderate their calcium intake, though the optimal level is simply not known," Kristal said. "Much more research is needed on factors that may prevent cancer recurrence in men treated for early-stage disease."

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The Fred Hutchinson Cancer Research Center, home of two Nobel Prize laureates, is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Fred Hutchinson receives more funding from the National Institutes of Health than any other independent U.S. research center. Recognized internationally for its pioneering work in bone-marrow transplantation, the center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. Fred Hutchinson is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest and is one of 41 nationwide. For more information, visit the center's Web site at http://www.fhcrc.org/.

Advancing Knowledge, Saving Lives

Contact: Kristen Lidke Woodward, kwoodwar@fhcrc.org, 206-667-5095, Fred Hutchinson Cancer Research Center

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