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Antioxidant blood levels key to MnSOD gene


Greater levels of selenium, vitamin E and the tomato nutrient lycopene have been shown to reduce prostate cancer in one out of every four Caucasian males -- those who inherit a specific genetic variation that’s particularly sensitive to oxidative stress.

Conversely, if carriers of this genetic variant have low levels of these vitamins and minerals, their risk of aggressive prostate increases substantially, as great as 10-fold, over their cohorts who maintain higher levels of these nutrients.

These results, published in the March 15 issue of the journal Cancer Research, were based on the analysis of 567 men diagnosed with prostate cancer between 1982 and 1995, and 764 cancer-free men from the Physicians Health Study (PHS). "This large prospective study provides further evidence that oxidative stress may be one of the important mechanisms for prostate cancer development and progression, and adequate intake of antioxidants, such as selenium, lycopene and vitamin E, may help prevent prostate cancer," said Haojie Li, M.D., Ph.D., a researcher at the Brigham and Women’s Hospital and Harvard Medical School.

Destructive molecules known as "free radicals" have been shown to team up with oxygen in the human body resulting in oxidative stress and what some scientists believe is an assortment of age-related ailments. As a result, many believe that consumption of antioxidants can slow that process. "Our study, as well as many other epidemiological studies, encourages dietary intake of nutrients such as lycopene from tomato products, or supplements for vitamin E and selenium to reduce risk of prostate cancer," said Li.

The initial goal of the PHS study was to assess the effect of aspirin and beta carotene on men’s health. Since blood samples collected in 1982 were available from many of the study’s participants, the research team decided to review variants for the gene that codes for manganese superoxide dismutatase (MnSOD), an important enzyme that works as an antioxidant in human cells to defend against disease. The MnSOD gene is passed from parents to offspring in one of three forms: VV, VA or AA. "Compared with men with the MnSOD VV or VA genotype, people with the AA genotype seem to be more sensitive to the antioxidant status," said Li. "Men with the AA genotype are more susceptible to prostate cancer if their antioxidant levels are low."

The study’s results found that a quarter of the men in the study carried the MnSOD AA genotype, half carried the VA genotype, and the remaining quarter carried the VV genotype. The results indicated that the VA and VV men were at equivalent risk for developing prostate cancer across all levels of antioxidants in their blood. Compared to MnSOD VV or VA carriers with low selenium – those men in the lowest quartile of the study group – MnSOD AA males had an 89 percent greater risk for developing aggressive prostate cancer if blood levels for selenium were low.

On the other hand, MnSOD AA carriers with high selenium – those men in the highest quartile – had a 65 percent lower risk than the MnSOD VV or VA males who maintained low levels of selenium. "The levels of selenium in the highest quartile of these men are not abnormally high," Li said. "Our range is neither extremely high nor extremely low."

While similar trends were observed for lycopene and vitamin E when tested independently, the contrast in relative risk was most pronounced for the men who had high blood levels for all three antioxidants combined. "Among men with the MnSOD AA genotype, we observed a 10-fold difference in risk for aggressive prostate cancer, when comparing men with high versus low levels of antioxidants combined," said Li. "In contrast, among men with the VV or VA genotype, the prostate cancer risk was only weakly altered by these antioxidant levels."

Similar interactions between dietary antioxidants and the variations in the MnSOD gene have previously been linked to risk for breast cancer.

Russell Vanderboom, Ph.D. | EurekAlert!
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