PHILADELPHIAEvidence 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 weve 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
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.
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 NCIs 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
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.
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 weve shown in some of
our previous trials, Dr. Albanes said.