Lycopene Doesn't Prevent Prostate Cancer, and Beta-Carotene Makes It Worse


SEATTLE -- Prostate cancer risk is unaffected by lycopene, and beta-carotene appears to triple the risk for aggressive forms of the malignancy, a large study showed.

SEATTLE, May 17 -- Lycopene, abundant in tomatoes and popularly thought to be particularly useful in preventing prostate cancer, has no effect on disease risk, a large prospective study showed.

What's more, high serum levels of beta-carotene, in the same family of carotenoid antioxidants as lycopene, appears to be associated with a three-fold increased risk for aggressive prostate cancer, found Ulrike Peters, Ph.D., M.P.H., of the Fred Hutchinson Cancer Research Center here, and colleagues.

Among more than then 28,000 men studied, those who had the highest serum levels of lycopene did not have a lower occurrence of prostate cancer or less aggressive tumors than men in the lowest tier, the investigators reported in the May issue of Cancer Epidemiology, Biomarkers & Prevention.

"It is disappointing, since lycopene might have offered a simple and inexpensive way to lower prostate cancer risk," Dr. Peters said. "Unfortunately, this easy answer just does not work."

The beta-carotene finding was unexpected, but not surprising, the researchers noted, given that beta-carotene is known to increase risk for lung cancer and cardiovascular disease among smokers.

"While it would be counter-productive to advise people against eating carrots and leafy vegetables, I would say to be cautious about taking beta-carotene supplements, particularly at high doses," Dr. Peters said.

The study was one of the largest, but not the only one, to find that lycopene was more hype than hope when it comes to prostate cancer prevention. In 2005, Peter Clark, M.D., of Wake Forest University, and colleagues, reported results of a trial intended to see if 36 men with recurrent prostate cancer could be protected by lycopene, as measured by PSA doubling time.

They found that the mean PSA doubling time at baseline was 3.7 years, and at study end was 4.1 years, a difference that was not statistically significant. In addition, the change in PSA level for a sustained period (PSA slope) was also not significantly different from baseline through one-year follow-up, Dr. Clark reported at the 2005 meeting of the American Urological Association.

But several large cohort studies, including the Health Professionals Follow-up Study, and the Physician's Health Study, reported that lycopene had a protective effect.

In the current study, Dr. Peters and colleagues conducted a nested case-control study involving men enrolled in the longitudinal NIH-funded Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early cancer detection and cancer risk factors.

Their goal was to investigate the association between pre-diagnostic serum carotenoids (including lycopene, ?-carotene, ?-carotene, ?-cryptoxanthin, lutein, and zeaxanthin) and the risk of prostate cancer among 28,243 men from the ages of 55 to 74 who were free of prostate cancer at the time of study enrollment.

The participants were screened at baseline with PSA and digital rectal exam, and were then followed through routine exams and screenings until first occurrence of prostate cancer, death, or the end of the trial in 2001. The men also completed health, food, and lifestyle questionnaires, and provided blood samples at study entry.

The investigators focused on 692 non-Hispanic white men with incident prostate cancer who were diagnosed one to eight years after study entry; there were not enough cases among Hispanic men or non-Hispanic black men for a significant analysis, the authors determined. They also looked at 844 randomly selected, matched controls.

Among the 692 cases, there were 270 aggressive cancers, 90 of which had regional invasion or distant metastasis, and 235 of which had a Gleason score of 7 or greater.

The researchers found no association between serum lycopene and total prostate cancer (odds ratio, 1.14, 95% confidence interval, 0.82-1.58 for the highest versus the lowest quintile, P for trend=0.28). Similarly, serum lycopene was not associated with a lower risk for aggressive cancer (odds ratio 0.99; 95% confidence interval, 0.62-1.57 for the highest versus lowest quintile; P for trend=0.433).

They did find, however, that ?-carotene levels were associated with an increased risk of aggressive prostate cancer (odds ratio, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile, P for trend=0.13).

In addition, ?-carotene was associated with a three-fold risk for regional or distant-stage disease (odds ratio 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile, P for trend=0.02). None of the other carotenoids they examined were associated with prostate cancer risk.

"Consistent with other recent publications," the investigators said, "these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention."

They acknowledged that their study was limited by the use of only a single serum sample, by the relatively short follow-up of eight years, and by the potential for residual confounding factors.

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