Drinking a glass of red wine a day may cut a man's risk of prostate cancer in half, and the protective effect appears to be strongest against the most aggressive forms of the disease, according to a new study led by investigators at Fred Hutchinson Cancer Research Center.

The findings, by Janet L. Stanford, Ph.D., and colleagues in Fred Hutchinson's Public Health Sciences Division, appear online in The International Journal of Cancer.

"We found that men who consumed four or more glasses of red wine per week reduced their risk of prostate cancer by 50%," Stanford said. "Among men who consumed four or more 4-ounce glasses of red wine per week, we saw about a 60% lower incidence of the more aggressive types of prostate cancer," said Stanford, senior author of the study. "The more clinically aggressive prostate cancer is where the strongest reduction in risk was observed."

Stanford and colleagues found no significant effects -- positive nor negative -- associated with the consumption of beer or hard liquor and no consistent risk reduction with white wine, which suggests that there must be a beneficial compound in red wine that other types of alcohol lack. That compound, Stanford and colleagues believe, may be an antioxidant called resveratrol, which is abundant in the skins of red grapes but much less so in the skins of white grapes. The compound is also found in peanuts and raspberries and is available as a dietary supplement, which has been suggested to protect against cardiovascular disease.

Laboratory studies indicate that resveratrol influences a variety of biological pathways that are important in cancer development. For example:

* As an antioxidant, it helps sweep dangerous, cancer-causing free radicals from the body.
* As a potent anti-inflammatory agent, it blocks certain enzymes that promote tumor development.
* The compound also reduces cell proliferation, curtailing the number of cell divisions that could lead to cancer or the continued growth of cancer cells.
* It also enhances apoptosis, or programmed cell death, which helps rid the body of cancerous cells.
* It may act as an estrogen, reducing levels of circulating male hormones such as testosterone that fuel the growth of prostate cancer.

While the researchers found that the risk of prostate cancer decreased 6% for every glass of red wine consumed per week, Stanford is quick to point out that research shows the law of diminishing returns comes into play when consumption increases beyond moderation.

"From a public-health standpoint, it's difficult to recommend any alcohol consumption given the risks associated with heavy consumption, from increased overall cancer risk to accidental injury and social problems. But for men who already are consuming alcohol, I think the results of this study suggest that modest consumption of red wine -- four to eight 4-ounce drinks per week -- is the level at which you might receive benefit. Clearly, other studies show that more than that may have adverse effects on health."

For the study, the researchers interviewed 753 newly diagnosed Seattle-area prostate-cancer patients as well as 703 healthy controls who served as a comparison group. Detailed information about tumor aggressiveness (such as tumor grade and disease stage) was obtained through the National Cancer Institute's Seattle-Puget Sound Surveillance, Epidemiology and End Results cancer registry.

"Even though this study is based on relatively small numbers, the results are very intriguing and suggest that the potential beneficial effect of red wine and resveratrol -- if indeed resveratrol is the active chemopreventive agent involved -- would be very important, because it's the more aggressive forms of prostate cancer than are most important to prevent," she said.

A particular strength of the study, Stanford said, is that the participants were relatively young, ranging in age from 40 to 64, and the majority were under 60.

"By focusing on men under age 65, whose incidence of prostate cancer is much lower than that of older men, we can tease out the effect of a particular environmental exposure on cancer risk, such as wine consumption, more easily than if we were looking at men across the entire age range," she said. This is particularly true when studying complex diseases such as prostate cancer in which numerous genetic and environmental factors are thought to play a role over an individual's lifetime.

Another strength of the study is that in addition to being surveyed about lifetime alcohol consumption, participants were asked about a variety of other risk factors for prostate cancer, such as diet, family history of cancer, screening for prostate cancer and tobacco use, all of which were taken into account and adjusted for when analyzing the data.

While the majority of studies to date have assessed the effects of overall alcohol use on prostate-cancer risk, fewer studies have attempted to compare the effects of wine versus beer versus hard liquor, and only one previous study has compared the impact of red versus white wine on prostate-cancer risk, said Stanford, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine.

The previous study, the Netherlands Cohort Study, evaluated prostate-cancer risk in relation to white and red wine consumption. Increased risks were found in men who consumed "white and fortified wines," but not red wine, as compared to nondrinkers, although there was not a consistent trend in risks with levels of intake. Interestingly, among men who consumed 15g or more of red wine per day (about one and a half glasses per day), there was an overall 18% reduction in risk and a 16% lower risk of advanced-stage prostate cancers. The Netherlands Cohort Study was initiated in 1986 and collected information by self-administered mailed questionnaires that asked about alcohol consumption during the prior year only. Thus, the Netherlands Cohort Study results only reflect associations with recent wine consumption, as investigators were unable to examine lifetime intake as was done in the current Fred Hutchinson study.

"One of the reasons we wanted to do this study is because overall, most of the scientific literature -- around 17 studies to date -- haven't shown a consistent relationship between alcohol consumption and prostate cancer," Stanford said. "Some have shown an increase, some a decrease, and most no association whatsoever. Part of the problem, we believe, is that few of the studies have attempted to sort out the effects of different types of alcohol intake over a man's lifetime."

Stanford and colleagues plan to seek funding to conduct a larger study to see if their results hold up. In collaboration with Norm Greenberg, Ph.D., of Fred Hutchinson's Clinical Research Division, they also plan to test the effects of resveratrol on mouse models of prostate cancer to see if giving mice this chemical compound will reduce the onset of prostate cancer and/or decrease the aggressiveness of the disease.

The first author of the study, W. Marieke Schoonen, M.S., formerly a graduate student in Stanford's group, is now a doctoral student at the London School of Hygiene and Tropical Medicine. The National Cancer Institute, National Institutes of Health and U.S. Department of Health and Human Services funded the research.