Evidence Mounting That Diet Plays a Role in Prostate Cancer

PHILADELPHIA—Evidence for the role of diet in the etiology of prostate cancer is mounting and with it, the possibility that nutritional factors can help prevent the disease, Demetrius Albanes, MD, said at the annual meeting of the Society of Nutritional Oncology Adjuvant Therapy. Dr. Albanes is a senior investigator with the Cancer Prevention Studies Branch of the National Cancer Institute.

Dr. Albanes said he begins with the proposition that environmental factors in general are known to play a causative role in prostate and other cancers. In the case of prostate cancer, mortality varies tremendously across populations.

“The one piece of information that we’ve noticed is that migrating populations moving from one host country to another will take up the prostate cancer rates of the new environment, even though their genetic make-up certainly will not have changed,” he said.

The nonnutritional environmental factors clearly related to prostate cancer are age, race (in the US, blacks are at increased risk), and family history (having first-degree relatives with prostate cancer raises the risk twofold). Cigarette smoking and sexually transmitted disease may also be contributory factors.

When the analysis turns to dietary factors, the key one that appears to be positively related to prostate cancer is dietary fat. Dr. Albanes explained that 15 of 22 case-controlled, prospective cohort studies have shown that higher total dietary fat intake is related to higher prostate cancer risk. Those studies that classified the type of fat consumed found that the highest prostate cancer incidence was related to animal fat.

In one study, men with the highest meat intake had a 40% higher risk of developing prostate cancer than men who ate the least meat, he said. Several studies have shown a connection between height and prostate cancer, with taller men at greater risk, a correlation that may reflect an early exposure to energy or fat.

“These studies suggest that energy balance throughout life may very well be associated with prostate carcinogenesis,” he said. The specific mechanisms might involve increased exposure to androgens or growth factors.

Carotenoids have long been viewed as a possible cancer preventive agent, but in prostate cancer, in particular, the findings are ambiguous.

In 12 of 28 studies, higher carotenoid or vegetable intake or biochemical status was associated with lower prostate cancer risk. But in 11 of the 28 studies, there was a direct association for total retinol or beta-carotene that was opposite of expectations: Individuals with higher beta-carotene or total retinol intake or blood levels were at somewhat increased risk.

Five of the 28 studies showed no relation between carotenoid or vitamin A intake and prostate cancer.

Several recent studies have focused on lycopene, which Dr. Albanes called a “free-radical quenching carotenoid found in tomato-based food.” Several studies have suggested that this strongly antioxidant, non-vitamin A carotenoid and tomato-based foods may be beneficial for prostate cancer.

“Actually, in a Harvard study, pizza turned out to be one of the most beneficial foods for preventing prostate carcinogenesis,” Dr. Albanes said.

Age may play a role in the effect of carotenoids, he added, but the exact effect still needs to be parsed out.

Vitamin E

The benefit of vitamin E supplementation in the reduction of prostate cancer has been demonstrated in a study whose main focus was lung cancer. The NCI’s Alpha Tocopherol, Beta-Carotene Cancer Prevention Trial was begun in the 1980s and included 29,000 men. Its primary focus was to explore whether beta-carotene and vitamin E reduced lung cancer risk, but the study looked at their effect on other cancers as well.

Dr. Albanes said that the reason for using these two agents was strong epidemiologic evidence for cancer protective associations, particularly for carotenoids and beta-carotene at that time and, to a lesser degree, for tocopherol. There was also laboratory research showing tumor inhibition.

The study found that vitamin E supplementation, 50 mg daily over 5 to 8 years, correlated with an approximately one-third reduction in the incidence of prostate cancer and a 40% reduction in prostate cancer mortality. The study also demonstrated a 20% risk elevation among those who took beta-carotene, though it was not statistically significant.

Selenium Studies

Selenium has also received much attention in human studies and in the lab. A 1998 study of the preventive effects of selenium, as measured in the toenails, showed the greatest association between increased selenium biochemical status and reduced prostate cancer risk. Those in the highest quintile of selenium status enjoyed approximately two-thirds reduction in prostate cancer risk, with a significant dose-response trend, such that those with the highest level had the lowest risk of prostate cancer, Dr. Albanes said.

These data mirrored those found in a 1996 study in which development of skin cancer was the primary endpoint. In this trial, selenium did not prevent skin cancer, but there was a 46% reduction in lung cancer and a nearly two-thirds reduction in prostate cancer.

The National Cancer Institute is now recruiting for a randomized study testing both alpha tocopherol, 400 mg daily, and 200 µg of elemental selenium. The subjects may receive either agent, both agents, or neither.

32,000 Participants

The primary endpoint of this trial will be prostate cancer, with several other secondary endpoints, including colorectal cancer and cardiovascular disease. The study will attempt to recruit 32,000 volunteers with no clinical evidence of disease at baseline.

“Hopefully, we will be able to confirm the very exciting and dramatic effects on prostate cancer that we’ve shown in some of our previous trials,” Dr. Albanes said.