Micronutrient Benefit For Prostate Cancer Ruled Out

OXFORD, England, Sept. 7 -- None of 10 micronutrients -- such as carotenoids, retinol, and tocopherols -- appears to help prevent prostate cancer, found investigators here.

The European Prospective Investigation into Cancer and Nutrition study found that none of the 10 micronutrients analyzed prevented prostate cancer, according to Timothy Key, D.Phil., of Oxford University and colleagues.

But men with high plasma levels of lycopene or all of the carotenoids taken together had a lower risk of being diagnosed with advanced cancer, Timothy Key, D.Phil., of Oxford University, and colleagues, reported in the September issue of the American Journal of Clinical Nutrition.

The bottom line, concluded Dr. Key and colleagues in the European Prospective Investigation into Cancer and Nutrition, is that none of the studies to date -- including several randomized controlled trials -- have demonstrated that micronutrients "have any clear effect on prostate cancer risk."

The study enrolled 137,001 men in eight European countries, whose blood was taken at baseline. After an average follow-up of six years, 966 new cases of prostate cancer were diagnosed among the study participants.

The researchers identified 1,064 matched controls who had not developed cancer, and compared plasma levels of the 10 micronutrients -- a-carotene, b-carotene, lycopene, lutein, zeaxanthin, b-cryptoxanthin, canthaxanthin, retinol, a-tocopherol, and b-tocopherol.

But a conditional logistic regression analysis, adjusted for smoking, alcohol intake, body mass index, marital status, physical activity, and education level, failed to find significant associations between any of the nutrients and prostate cancer risk, the researchers said.

On the other hand, for lycopene and the sum of the carotenoids taken together there was "evidence of heterogeneity" between the associations with risk of either localized or advanced disease.

Neither was associated with the risk of localized disease but both were inversely associated with the risk of advanced disease, the researchers found. Specifically:

• For men in the highest fifth of plasma concentrations of lycopene, compared with those in the lowest fifth, the risk of advanced disease was 0.40, with a 95% confidence interval from 0.19 to 0.88. The trend was significant at P=0.05.
• For men in the highest fifth of plasma concentrations of the sum of all of the carotenoids, compared to those in the lowest fifth, the risk of advanced disease was 0.35, with a 95% confidence interval from 0.17 to 0.78. The trend was significant at P=0.04.

Because lycopene is a carotenoid, the association between disease and the sum of the carotenoids is likely driven by lycopene, the researchers said.

But the finding is not clear evidence of a health benefit, the researchers said. The association could be based on "a protective effect, an association of dietary choice with delayed detection of prostate cancer, reverse causality, or other factors," they said.

By "reverse causality," Dr. Key and colleagues said, they mean that the advanced cancer might have been present -- but subclinical -- at the time blood was collected and might have influenced plasma concentrations of the nutrients in some way.

Council of the U.K., the Stroke Association of the U.K., the British Heart Foundation; the U.K. Department of Health, the U.K. Food Standards Agency, the Wellcome Trust, the Greek Ministry of Health; the Greek Ministry of Education, the Italian Association for Research on Cancer, the Italian National Research Council, the Dutch Ministry of Public Health, Welfare and Sports, the Dutch Ministry of Health, the Dutch Prevention Funds, the LK Research Funds, the Dutch ZON, the Swedish Cancer Society, and the Swedish Scientific Council.

None of the authors reported a conflict of interest.