© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Zinc Supplement Use and Risk of Prostate Cancer
Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD (MFL); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (EG)
Correspondence to: Michael F. Leitzmann, MD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Blvd., EPS-MSC 7232, Bethesda, MD 20892 (e-mail: leitzmann{at}mail.nih.gov)
We read with interest the letter by Chang et al. reporting no association between zinc supplement use and the risk of prostate cancer in a Swedish case-control study. By comparison, our results (1) suggest that high intake of supplemental zinc is associated with an increased risk of advanced prostate cancer. There are several possible explanations for these discrepant findings. The proportion of subjects in our study with zinc supplement exposure was greater than that in the Swedish study. For example, only 2.5% of the base population in the Swedish study reported using zinc supplements, whereas 25% of the subjects in our study reported using zinc supplements. In addition, it is likely that the doses of zinc consumed by subjects in the Swedish study were largely compatible with the recommended dietary allowance of 11 mg/day of zinc for men, an intake level that is not associated with an increase in prostate cancer risk (1). By comparison, our study included 4374 men whose zinc intake exceeded the current recommended dietary allowance by at least twofold. Furthermore, it is possible that the duration of zinc supplement use is critical for an increase in prostate cancer risk. In our study, 6177 men reported consistent use of zinc supplements for 10 years or longer. Finally, the apparent adverse effect of zinc supplement use that we observed was restricted to cases of advanced prostate cancer.
To further address the relationship between high doses and long duration of zinc supplement use and the risk of advanced prostate cancer, we present data on intake and duration of supplemental zinc use in combination (Table 1). The risk of advanced prostate cancer was higher among men with the highest intake and the longest duration of zinc supplement use than among nonusers. By comparison, zinc supplement use for fewer than 10 years was not statistically significantly related to the risk of advanced prostate cancer, even at doses exceeding the recommended dietary allowance. These data suggest that the use of high doses of zinc supplements for a long time (consistent with long-term zinc toxicity) may be required to increase the risk of advanced prostate cancer.
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The findings reported by Chang et al. showing a lack of association between supplemental zinc use and risk of prostate cancer do not rule out the possibility of an association between advanced prostate cancer and excessive intakes of supplemental zinc for at least a decade. Zinc effects are likely to vary by dose, as suggested by circumstantial evidence showing that both insufficient and surplus amounts of zinc are associated with undesirable metabolic effects potentially related to prostate cancer. For example, it is recognized that zinc deficiency causes a decline in immunologic competence (2), whereas high intakes of supplemental zinc are also associated with an impaired immune response (3). Future studies designed to address the effects of both long-term zinc deficiency and long-term zinc oversupply should clarify the association between zinc intake and prostate carcinogenesis.
REFERENCES
1 Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 2003;95:1004–7.
2 Frost P, Chen JC, Rabbani I, Smith J, Prasad AS. The effect of zinc deficiency on the immune response. Prog Clin Biol Res 1977;14:143–53.[Medline]
3 Chandra RK. Excessive intake of zinc impairs immune responses. JAMA 1984;252:1443–6.
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J Natl Cancer Inst 2004 96: 1108.
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