PHILADELPHIA—Eating a concentrated extract of freeze-dried broccoli sprouts might inhibit bladder cancer by delivering a protective factor right where the bladder is most at risk. Eating three helpings a month of raw (but not cooked) cruciferous vegetables might reduce bladder cancer risk, researchers reported at the AACR's 6th Annual International Conference on Frontiers in Cancer Prevention Research.
A research team led by Rex Munday, PHD, from Ruakura Agricultural Research Center, Hamilton, New Zealand, induced bladder cancer in rats and had them eat a freeze-dried aqueous extract of broccoli sprouts. They found that the incidence, multiplicity, size, and progression of bladder cancer were all inhibited by the extract, which caused no histological changes in the bladder (abstract B149).
"This extract cut cancer incidence by 2.6-fold, inhibited cancer progression, and caused no adverse effects in the bladder," senior author Yuesheng Zhang, MD, PHD, professor in the Department of Cancer Prevention and Control, Ros-well Park Cancer Institute, said at an AACR press briefing. Dr. Zhang said that broccoli sprouts have 30 times more isothiocyanates (ITCs) than mature broccoli, and the freeze-dried extract had 600 times more ITCs by weight than fresh whole broccoli.
More than 70% of the ingested ITCs were excreted in the urine within 12 hours after a single oral dose. Urinary ITC levels were two to three orders of magnitude higher than plasma concentrations in the treated rats, and bladder tissue ITC levels were also higher than hepatic ITC levels, indicating that ITCs from the extract are selectively delivered to the bladder epithelium through urinary excretion.
Raw better than cooked
A related study, also from Roswell Park researchers, suggests that the way cruciferous vegetables are prepared may have major effects on their anticancer properties (abstract B47).
Li Tang, MD, PHD, and her colleagues conducted a case-control study of 275 patients with incident primary bladder cancer and 825 cancer-free controls to determine whether the inconsistent results of previous studies of cruciferous vegetable intake and bladder cancer risk were due to differences in how the vegetables were prepared. Patients completed a comprehensive questionnaire that included prediagnosis diet, occupational exposure, and other bladder cancer risk factors such as smoking history.
"Cooking can substantially reduce or destroy ITCs, and could account for study inconsistencies," said Dr. Tang, a postdoctoral fellow in the Department of Cancer Prevention and Control.
Bladder cancer risk was significantly reduced by intake of raw cruciferous vegetables (adjusted odds ratio [OR] for highest vs lowest category, 0.57). This did not apply to cooked cruciferous vegetables. There appeared to be a dose-response trend (P = .004). Total fruit, total vegetable, and total cruciferous vegetable intakes had no significant effect on bladder cancer risk.
Nonsmokers who ate three or more servings monthly of raw cruciferous vegetables had the greatest risk reduction (adjusted OR, 0.27), compared to smokers with lower cruciferous vegetable intake.
"Raw cruciferous vegetables such as broccoli, cabbage, and cauliflower are better than their cooked counterparts in terms of bladder cancer prevention. Intake of three or more helpings of such vegetables per month may reduce the risk of bladder cancer by 37%. Smokers, even heavy smokers, may benefit from the intake of raw cruciferous vegetables. Risk reduction for smokers was 40% to 54%," Dr. Tang said at the press briefing.
Ernest T. Hawk, MD, MPH, head of the Division of Cancer Prevention and Population Sciences, M.D. Anderson Cancer Center, put the two vegetable studies into perspective for ONI.
"ITCs are well known to inhibit cancer development in vitro by modifying the metabolism of carcinogens," he said. "The Zhang study addresses a key preliminary question before contemplating large-scale trials in humans. It shows that the active substance in broccoli sprouts, ITCs, becomes concentrated in the urine, which suggests that it may be particularly effective at inhibiting bladder cancer.
The study of cooked vs raw cruciferous vegetable intake is useful for hypothesis generation, but should not be the basis for recommendations to the public because it is a retrospective observational study, he said. Dr. Hawk also wondered how many other variables had been included in the analysis and how many times the data had been sliced. "The more things you look at, the more likely you are to find something statistically significant purely by chance, which is one of the reasons that we typically do not make recommendations to the public based on observational studies alone," he said. A major potential confounder that should be explored in future studies is whether consumption of raw cruciferous vegetables is just a marker for a generally more healthy lifestyle.
The most intriguing aspect of this study is that it might help explain the conflicting conclusions about cruciferous vegetables and cancer protection reported by other studies: "Maybe the key factor is whether they are cooked vs raw," he said.