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Epidemiology and Prevention |
Division of Preventive Medicine [C. H. H.] and Channing Laboratory [J. M., E. G., M. J. S.], Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115; Departments of Epidemiology [C. H. H., M. J. S.] and Nutrition [E. G., W. W., F. M. S., M. J. S.], Harvard School of Public Health, Boston, Massachusetts 02115; and Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois 60611 [P. H. G.]
ABSTRACT
Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer.
We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and ß-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (
- and ß-carotene, ß-cryptoxanthin, lutein, and lycopene) plus - and 
-tocopherol and retinol using high-performance liquid chromatography. Results for plasma ß-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (CIs), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active ß-carotene or placebo in the trial.
Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54–1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34–0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to ß-carotene supplements. However, in the ß-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher -tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level.
These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming ß-carotene supplements. For men with low lycopene, ß-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.
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C. H. van Gils, R. M. Bostick, M. C. Stern, and J. A. Taylor Differences in Base Excision Repair Capacity May Modulate the Effect of Dietary Antioxidant Intake on Prostate Cancer Risk: An Example of Polymorphisms in the XRCC1 Gene Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1279 - 1284. [Abstract] [Full Text] [PDF]
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E. Giovannucci A Review of Epidemiologic Studies of Tomatoes, Lycopene, and Prostate Cancer Experimental Biology and Medicine, November 1, 2002; 227(10): 852 - 859. [Abstract] [Full Text] [PDF]
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E. Giovannucci, E. B. Rimm, Y. Liu, M. J. Stampfer, and W. C. Willett A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk J Natl Cancer Inst, March 6, 2002; 94(5): 391 - 398. [Abstract] [Full Text] [PDF]
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L. Chen, M. Stacewicz-Sapuntzakis, C. Duncan, R. Sharifi, L. Ghosh, R. v. Breemen, D. Ashton, and P. E. Bowen Oxidative DNA Damage in Prostate Cancer Patients Consuming Tomato Sauce-Based Entrees as a Whole-Food Intervention J Natl Cancer Inst, December 19, 2001; 93(24): 1872 - 1879. [Abstract] [Full Text] [PDF]
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E. Kotake-Nara, M. Kushiro, H. Zhang, T. Sugawara, K. Miyashita, and A. Nagao Carotenoids Affect Proliferation of Human Prostate Cancer Cells J. Nutr., December 1, 2001; 131(12): 3303 - 3306. [Abstract] [Full Text] [PDF]
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D. Heber and S. Bowerman Applying Science to Changing Dietary Patterns J. Nutr., November 1, 2001; 131(11): 3078S - 3081. [Abstract] [Full Text] [PDF]
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O. Kucuk, F. H. Sarkar, W. Sakr, Z. Djuric, M. N. Pollak, F. Khachik, Y.-W. Li, M. Banerjee, D. Grignon, J. S. Bertram, et al. Phase II Randomized Clinical Trial of Lycopene Supplementation before Radical Prostatectomy Cancer Epidemiol. Biomarkers Prev., August 1, 2001; 10(8): 861 - 868. [Abstract] [Full Text] [PDF]
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Q.-Y. Lu, J.-C. Hung, D. Heber, V. L. W. Go, V. E. Reuter, C. Cordon-Cardo, H. I. Scher, J. R. Marshall, and Z.-F. Zhang Inverse Associations between Plasma Lycopene and Other Carotenoids and Prostate Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2001; 10(7): 749 - 756. [Abstract] [Full Text] [PDF]
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T. W.-M. Boileau, S. K. Clinton, S. Zaripheh, M. H. Monaco, S. M. Donovan, and J. W. Erdman Jr. Testosterone and Food Restriction Modulate Hepatic Lycopene Isomer Concentrations in Male F344 Rats J. Nutr., June 1, 2001; 131(6): 1746 - 1752. [Abstract] [Full Text]
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 J. Brown, T. Byers, K. Thompson, B. Eldridge, C. Doyle, A. M. Williams, and American Cancer Society Workgroup on Nutrition and Nutrition During and After Cancer Treatment: A Guide for Informed Choices by Cancer Survivors CA Cancer J Clin, May 1, 2001; 51(3): 153 - 181. [Abstract] [Full Text] [PDF]
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K. Imaida, S. Tamano, K. Kato, Y. Ikeda, M. Asamoto, S. Takahashi, Z. Nir, M. Murakoshi, H. Nishino, and T. Shirai Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis Carcinogenesis, March 1, 2001; 22(3): 467 - 472. [Abstract] [Full Text] [PDF]
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E. Giovannucci {{gamma}}-Tocopherol: a New Player in Prostate Cancer Prevention? J Natl Cancer Inst, December 20, 2000; 92(24): 1966 - 1967. [Full Text] [PDF]
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K. J. Helzlsouer, H.-Y. Huang, A. J. Alberg, S. Hoffman, A. Burke, E. P. Norkus, J. S. Morris, and G. W. Comstock Association Between {{alpha}}-Tocopherol, {{gamma}}-Tocopherol, Selenium, and Subsequent Prostate Cancer J Natl Cancer Inst, December 20, 2000; 92(24): 2018 - 2023. [Abstract] [Full Text] [PDF]
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A. V. Rao and S. Agarwal Role of Antioxidant Lycopene in Cancer and Heart Disease J. Am. Coll. Nutr., October 1, 2000; 19(5): 563 - 569. [Abstract] [Full Text] [PDF]
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 S. Agarwal and A. V. Rao Tomato lycopene and its role in human health and chronic diseases Can. Med. Assoc. J., September 1, 2000; 163(6): 739 - 744. [Abstract] [Full Text] [PDF]
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L. N. Kolonel, J. H. Hankin, A. S. Whittemore, A. H. Wu, R. P. Gallagher, L. R. Wilkens, E. M. John, G. R. Howe, D. M. Dreon, D. W. West, et al. Vegetables, Fruits, Legumes and Prostate Cancer: A Multiethnic Case-Control Study Cancer Epidemiol. Biomarkers Prev., August 1, 2000; 9(8): 795 - 804. [Abstract] [Full Text]
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A. Azzi, I. Breyer, M. Feher, M. Pastori, R. Ricciarelli, S. Spycher, M. Staffieri, A. Stocker, S. Zimmer, and J.-M. Zingg Specific Cellular Responses to {alpha}-Tocopherol J. Nutr., July 1, 2000; 130(7): 1649 - 1652. [Abstract] [Full Text]
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B. Watzl, A. Bub, M. Blockhaus, B. M. Herbert, P. M. Lührmann, M. Neuhäuser-Berthold, and G. Rechkemmer Prolonged Tomato Juice Consumption Has No Effect on Cell-Mediated Immunity of Well-Nourished Elderly Men and Women J. Nutr., July 1, 2000; 130(7): 1719 - 1723. [Abstract] [Full Text]
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T. Narisawa, Y. Fukaura, M. Hasebe, S. Nomura, S. Oshima, and T. Inakuma Prevention of N-Methylnitrosourea-Induced Colon Carcinogenesis in Rats by Oxygenated Carotenoid Capsanthin and Capsanthin-Rich Paprika Juice Experimental Biology and Medicine, June 1, 2000; 224(2): 116 - 122. [Abstract] [Full Text]
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M. J. Wargovich, A. Jimenez, K. McKee, V. E. Steele, M. Velasco, J. Woods, R. Price, K. Gray, and G. J. Kelloff Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression Carcinogenesis, June 1, 2000; 21(6): 1149 - 1155. [Abstract] [Full Text] [PDF]
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T. W. M. Boileau, S. K. Clinton, and J. W. Erdman Jr. Tissue Lycopene Concentrations and Isomer Patterns Are Affected by Androgen Status and Dietary Lycopene Concentration in Male F344 Rats J. Nutr., June 1, 2000; 130(6): 1613 - 1618. [Abstract] [Full Text]
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G. J. Kelloff, J. A. Crowell, V. E. Steele, R. A. Lubet, W. A. Malone, C. W. Boone, L. Kopelovich, E. T. Hawk, R. Lieberman, J. A. Lawrence, et al. Progress in Cancer Chemoprevention: Development of Diet-Derived Chemopreventive Agents J. Nutr., February 1, 2000; 130(2): 467 - 467. [Abstract] [Full Text]
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J. H. Cohen, A. R. Kristal, and J. L. Stanford Fruit and Vegetable Intakes and Prostate Cancer Risk J Natl Cancer Inst, January 5, 2000; 92(1): 61 - 68. [Abstract] [Full Text] [PDF]
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A. R. Kristal, J. L. Stanford, J. H. Cohen, K. Wicklund, and R. E. Patterson Vitamin and Mineral Supplement Use Is Associated with Reduced Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 1999; 8(10): 887 - 892. [Abstract] [Full Text]
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J. M. Chan, M. J. Stampfer, J. Ma, E. B. Rimm, W. C. Willett, and E. L. Giovannucci Supplemental Vitamin E Intake and Prostate Cancer Risk in a Large Cohort of Men in the United States Cancer Epidemiol. Biomarkers Prev., October 1, 1999; 8(10): 893 - 899. [Abstract] [Full Text]
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E. Giovannucci RESPONSE: Re: Tomatoes, Tomato-based Products, Lycopene, and Prostate Cancer: Review of the Epidemiologic Literature J Natl Cancer Inst, August 4, 1999; 91(15): 1331a - 1331a. [Full Text]
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 G. Ronen, L. Carmel-Goren, D. Zamir, and J. Hirschberg An alternative pathway to beta -carotene formation in plant chromoplasts discovered by map-based cloning of Beta and old-gold color mutations in tomato PNAS, September 26, 2000; 97(20): 11102 - 11107. [Abstract] [Full Text] [PDF]
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