Re: Zinc supplement use and risk of prostate cancer.

Leitzmann et al. (1) recently reported that men who consumed more than 100 mg/day of supplemental zinc or who took supplemental zinc for at least 10 years had an approximately twofold-elevated risk of advanced prostate cancer compared with nonusers. Given these provocative findings, we investigated the relationship between zinc supplement use and the risk of prostate cancer in a recently completed population-based case– control study in Sweden that included 1499 prostate cancer case patients and 1130 control subjects. After granting informed consent, participants completed a questionnaire that assessed possible risk factors for prostate cancer, including supplemental zinc intake. Frequency of intake was recorded as the number of tablets consumed per week and the number of months per year tablets were used; duration of use was recorded as total number of years. This study was approved by the Karolinska Institute and Umeå University Ethics Committees and was funded by the Swedish Cancer Society. Use of supplemental zinc at least 1 year prior to completion of the questionnaire was reported by 3.4% (n 51) of case patients and 2.5% (n 28) of control subjects. After adjusting for age, we observed no statistically significant difference in the prevalence of supplemental zinc use between case patients and control subjects (odds ratio 1.3, 95% confidence interval 0.8 to 2.1). Further multivariate adjustment for possible confounders, including height, body mass index, family history of prostate cancer, smoking status, alcohol intake, and use of other nutritional supplements, did not appreciably affect the results. The association did not vary for risk of localized versus advanced disease (advanced prostate cancer was defined as tumor stage 3, nodal stage 1, metastatic stage 1, differentiation grade 3, Gleason score 8, and/or serum prostate-specific antigen 100; localized prostate cancer was defined as case patients not meeting the preceding criteria) or for risk of sporadic versus familial or hereditary disease (familial prostate cancer was defined as case patients with two firstor second-degree relatives with prostate cancer; hereditary prostate cancer was defined as case patients with 3 firstor second-degree relatives with prostate cancer; sporadic prostate cancer was defined as case patients not meeting the preceding criteria). In addition, we observed no statistically significant difference in prostate cancer risk between supplement users and nonusers when supplemental zinc use was categorized by frequency ( 1 tablet/day versus 1 tablet/day), duration ( 5 years versus 5 years), or cumulative exposure ( 200 total tablets versus 200 total tablets, or total tablets measured on a continuous scale). Overall, our findings differ from those of Leitzmann et al. (1) and Kolonel et al. (2), who reported that greater zinc consumption is associated with an increased risk of prostate cancer. Our results also differ from those of Kristal et al. (3), who reported that supplemental zinc intake is associated with decreased risk of prostate cancer. Rather, the lack of association between zinc supplement use and prostate cancer risk observed in our study is consistent with the null finding reported by Lee et al. (4). Our study had limited power to detect any association with risk of prostate cancer or to analyze a dose–response relationship in detail because of the low prevalence of supplemental zinc use among the case patients and the control subjects. Recent studies have found that use of complementary medicine, including zinc supplements, is common in men with prostate cancer (5,6). Thus, if the case patients in our study were prompted to use zinc supplements because of early disease, any inverse association between predisease zinc intake and risk of prostate cancer would have been obscured. Results of further investigations on zinc consumption in prostate cancer development, especially those from large studies with prospectively collected exposure data, should clarify this relationship. ELLEN T. CHANG MARIA HEDELIN HANS-OLOV ADAMI HENRIK GRÖNBERG KATARINA A. BÄLTER