A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands) Agnes G. Schuurman Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands R. Alexandra Goldbohm Department of Consumer Research and Epidemiology, TNO Nutrition and Food Research Institute, PO Box 360, 3700 AJ Zeist, the Netherlands Henny A. M. Brants Department of Consumer Research and Epidemiology, TNO Nutrition and Food Research Institute, PO Box 360, 3700 AJ Zeist, the Netherlands Piet A. van den Brandt Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands. Ph.: +31 43 388 23 61; Fax: +31 43 388 41 28; Email: PA.vandenBrandt@epid.unimaas.nl Abstract Objectives: The roles of retinol, vitamins C and E, and carotenoids as risk factors for prostate carcinoma are still questionable. We evaluated these in the Netherlands Cohort Study. Methods: The cohort study consisted of 58,279 men ages 55–69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intakes of retinol, vitamins C and E, and several carotenoids were measured by means of a 150-item semi-quantitative food-frequency questionnaire. Results: In multivariate analyses a positive association with prostate cancer risk was observed for intake of ß-cryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94, 1.01, 1.16, 1.41; p-trend <0.01. For intake of retinol, vitamins C and E and other carotenoids (a-carotene, ß-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for vitamin supplement use were decreased, but not significantly. Among nondrinkers, nonsignificant inverse associations were observed for intake of retinol, a-carotene, and ß-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60, and 0.76, respectively). Among drinkers, ß-cryptoxanthin was positively associated (RR highest vs lowest quintile = 1.40). Conclusions: These data show a positive association between ß-cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol, a-carotene, and ß-carotene among nondrinkers; this suggests an interaction between vitamins and alcohol consumption, which needs confirmation. Lycopene was not associated with prostate cancer. carotenoids,inconsistencies in results from several studies exist (discussed below). If an interaction between vitamin or carotenoid intake and alcohol consumption exists,different proportions of drinkers and nondrinkers in previous studies may explain the inconsistent results observed thus far. In the NLCS a lower intake of several nutrients among drinkers of alcoholic beverages com- pared to nondrinkers could not explain our .ndings (data not shown). We do not,however,have an obvious biological explanation for a potential interaction e .ect between vitamins or carotenoids and alcohol in prostate cancer etiology. Therefore,mechanistic research is warranted in addition to epidemiological studies. In our study we found no association between intake of retinol and overall prostate cancer risk,but among nondrinkers a strong inverse association was observed; protective effects of supplements containing vitamin A were suggestive. In previous prospective studies no association with vitamin A intake [8,25 ]or vitamin A supplements [26 ]was shown. Cohort studies using serum retinol levels found positive [27 –29 ],no [9,30,31 ]or inverse associations [32 –34 ]. Case –control studies on retinol were equally diverse in results (e.g.refs.10,35 –38). Vitamin C is mostly known for its antioxidant capacity [1 ].For prostate cancer,however,mostly no effect of vitamin C intake levels [8,26 ],serum levels [27 ], or vitamin C supplements [26 ]was observed,and also in the NLCS no association was apparent. Only for supplements containing vitamin C was a slight nonsig- nificant decrease in risk observed. One cohort study indicated an increased risk only in the highest quartile of intake;no trend in risk was observed [39 ]. Most case – control studies reported null associations for vitamin C in relation to risk of prostate cancer (e.g.refs.35,37,40, 41);two studies reported a positive association [36,38 ]. The antioxidative property of vitamin E or the enhance- ment of immune functions might be mechanisms by which (prostate)cancer incidence is reduced [3,42 ]. The ATBC trial showed a 32%decreased prostate cancer incidence in subjects receiving a tocopherol [3 ]. In the NLCS,however,no effect of dietary intake of vitamin E was found,but subjects taking supplements containing vitamin E showed nonsignificant decreased risks. No associations were shown in other cohort studies using intake [8,26,42 ]or serum levels [9,31,33,42 –44 ]or vitamin E supplements [26 ]. Case –control studies showed inconsistent results (e.g.refs.37,40,41). b carotene may act as an antioxidant;also,via its conversion to vitamin A or via an enhancement of immunologic function,a protective effect of this carot- enoid may be explained [1 ]. In the NLCS no clear associations emerged for intake of b carotene and overall prostate cancer risk. In one out of the three chemopre- ventive trials an adverse effect of b carotene was ob- served [3 ],in the other two trials b carotene showed no e .ect on prostate cancer risk [4,5 ]. In other cohort studies,intake [8,25,26,39 ]or serum levels [33 ]of b carotene were also not associated with risk of prostate cancer,or were positively associated [9,28 ]. Case – control studies were also inconsistent (e.g.refs.37,40). Few studies have evaluated specific carotenoids besides b carotene in relation to prostate cancer occur- rence.For intake of b cryptoxanthin a positive asso- ciation was observed in our study. Regarding intake, two case –control studies showed a positive association [10,37 ],while one cohort study found no association [8 ]. A positive association with serum b cryptoxanthin levels was also found in one cohort study [9 ],but no association in another [31 ]. Consistent with our obser- vation,we earlier found [19 ]a positive association with intake of citrus fruit (particularly oranges,an important source of b cryptoxanthin). Although we cannot rule out that our finding is a chance finding,further research into this issue and into its biological plausibility seems warranted. A significant inverse trend in risk was observed for intake of lycopene in the health profes- sionals follow-up study [8 ],but in another study no association was observed for serum levels [9 ]. In three nested case –control studies serum lycopene levels were also inversely related to prostate cancer risk [31,33,43 ] but nonsigni .cantly in two [33,43 ]. A role of lycopene in prostate cancer carcinogenesis is not inconceivable because lycopene is an e .cient scavenger of singlet oxygen [8,45 ]. Comparable to our results,in three other studies with prospectively collected exposure data, intake [8 ]and serum levels [9,31 ]of both a carotene and lutein were found not to be related to prostate cancer risk. Inverse associations for users of vitamin supplements were suggestive but statistically nonsignificant in our study. Since it has been shown that vitamin supplement users have cancer-related behaviors that are different from non-users of vitamin supplements [46 ],confound- ing might explain some of our findings regarding vitamin supplement use. For example,in the United States supplement users have been shown to have had a prostate-specific antigen (PSA)test twice as likely as nonusers,to take aspirin regularly,exercise more often, and eat more vegetables and fruit and less fat [46 ]. However,during our follow-up period PSA testing was not a common screening routine in the Netherlands and therefore we should not expect a confounding effect of this factor. Moreover,if supplement users more often had a PSA test an increased risk of overall prostate cancer would be expected,while we observed a decrease in risk. Apart from PSA,supplement users might have more regular check-ups,and this might partly explain why their risk of advanced cancer is lower. Indeed, supplement users had proportionally less advanced cancer than nonusers in our study (42%versus 51%). In summary,we found a positive association between b cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol,a carotene, and b carotene among nondrinkers;this suggests an interaction between vitamins and alcohol consumption, which needs confirmation.Lycopene was not associated with prostate cancer. Acknowledgements We are indebted to the participants of this study and further wish to thank the regional cancer registries (IKA,IKL,IKMN,IKN,IKO,IKR,IKST,IKW, IKZ),and the Dutch national data base of pathology (PALGA);Dr A.Volovics for statistical advice;S.van de Crommert,J.Nelissen,C.de Zwart,M.Moll,W.van Dijk,P.Florax,and A.Pisters for assistance;and H. van Montfort,R.Schmeitz,T.van Montfort,M. Zeegers,and M.de Leeuw for programming and statistical assistance. The Netherlands Cohort Study was supported by the Dutch Cancer Society. Cancer Causes and Control 13 (6): 573-582, August 2002 Copyright © 2002 Kluwer Academic Publishers All rights reserved Ann's NOTE: As we have recently noted, most people in these types of studies DO NOT eat much healthy food. Sometimes these 'subjects' are not getting more than one fruit or vegetable a day. We will try to get more information on this one. 28 citations Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.