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NUTRITION AND CANCER, 59(1), 46–53 C 2007, Lawrence Erlbaum Associates, Inc. Copyright 

Plasma Carotenoids and Prostate Cancer: A Population-Based Case-Control Study in Arkansas Jianjun Zhang, Ishwori Dhakal, Angie Stone, Baitang Ning, Graham Greene, Nicholas P. Lang, and Fred F. Kadlubar

Abstract: Carotenoids possess antioxidant properties and thus may protect against prostate cancer. Epidemiological studies of dietary carotenoids and this malignancy were inconsistent, partially due to dietary assessment error. In this study, we aimed to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in a population-based case-control study in Arkansas. Cases (n = 193) were men with prostate cancer diagnosed in 3 major hospitals, and controls (n = 197) were matched to cases by age, race, and county of residence. After adjustment for confounders, plasma levels of lycopene, lutein/zeaxanthin, and β-cryptoxanthin were inversely associated with prostate cancer risk. Subjects in the highest quartile of plasma lycopene (513.7 µg/l) had a 55% lower risk of prostate cancer than those in the lowest quartile (140.5 µg/l; P trend = 0.042). No apparent association was observed for plasma α-carotene and β-carotene. Further adjustment for the other 4 carotenoids did not materially alter the risk estimates for plasma lycopene, lutein/zeaxanthin, and β-cryptoxanthin but appeared to result in an elevated risk with high levels of plasma α-carotene and β-carotene. The results of all analyses did not vary substantially by age, race, and smoking status. This study added to the emerging evidence that high circulating levels of lycopene, lutein/zeaxanthin, and β-cryptoxanthin are associated with a low risk of prostate cancer.

Introduction Prostate cancer is the most common cancer and third leading cause of cancer death in men in the United States (1). Large international variation inincidence (2), rapidly el-

evated risk among Asian immigrants to North America (3,4), and marked changes in incidence among some populations within a relatively short period of time (5,6) suggest that environmental, especially dietary, factors play a vital role in the etiology of prostate cancer (7–9). However, the effects of specific nutrients and foods on the occurrence of this malignancy are not well understood, although some epidemiological studies have shown that high intakes of fat (particularly saturated fat); meats cooked at high temperature; and milk and low intakes of selenium, vegetables, and fruits were associated with an increased risk of prostate cancer (7–11). Carotenoids are a family of over 600 compounds, and these natural pigments are synthesized by plants and bacteria (12). Yellow, orange, and red vegetables and fruits are rich sources of carotenoids (12). Because many carotenoids are capable of functioning as antioxidants to quench singlet oxygen, they have been hypothesized to protect against conditions related to oxidative stress such as cancer, cardiovascular diseases, and osteoporosis (8,9,13,14). Most studies examining the relation between dietary carotenoids and prostate cancer have been confined to lycopene and β-carotene, and the results obtained were inconsistent (15–21). Food frequency questionnaires are a dietary assessment instrument that is most commonly used in epidemiological studies (22). The discrepant results are, at least in part, attributable to the measurement errors resulting from recall bias occurred during the administration of food frequency questionnaires. Plasma carotenoids are objective biomarkers of dietary intake of carotenoids (22). To date, however, few studies have measured plasma or serum carotenoids and evaluated their associations with prostate cancer. Therefore, the primary purpose of this study was to investigate the relation between plasma concentrations of carotenoids and the risk of prostate cancer in African-American and White men in Arkansas.

J. Zhang, I. Dhakal, and F. F. Kadlubar are affiliated with the Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR. J. Zhang, G. Greene, N. P. Lang, and F. F. Kadlubar are affiliated with the Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR. A. Stone and N. P. Lang are affiliated with the Central Arkansas Veterans Healthcare System, Little Rock, AR. A. Stone and B. Ning are affiliated with the Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AR. G. Greene and N. P. Lang are also affiliated with the Department of Surgery, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR.

Materials and Methods Study Population A population-based case-control study of prostate cancer was conducted from 1998 to 2003 in Arkansas. Because of budgetary constraints, this study includes a total of 193 cases (103 Whites, 90 African Americans) and 197 controls (95 Whites, 102 African Americans), which was a random subset of 618 cases (439 Whites, 179 African Americans) and 403 controls (257 Whites, 146 African Americans) recruited in the main study. African Americans were oversampled to explore whether the relation between plasma carotenoids and prostate cancer risk differed by race. The design and methodology of the main study have been described in detail elsewhere (23,24). Briefly, men, aged 40 to 80 yr who were diagnosed with primary, incident, histologically confirmed prostate cancer were recruited within 3 mo of diagnosis. Cases were ascertained from 3 major hospitals in central Arkansas: the University Hospital of the University of Arkansas for Medical Sciences, the Central Arkansas Veterans Health Care System (CAVHCS) in Little Rock, and the Jefferson Regional Medical Center in Pine Bluff, Arkansas. Controls were randomly selected from the source population that gave rise to cases. Specifically,controls were recruited from 3 sources: the Arkansas State Drivers’ License records, Centers for Medicare and Medicaid records, and a mass-mailing database. This database contained contact information for approximately 89% of Arkansas residents, and 68% of the controls recruited were selected from this source. Controls were frequency matched to cases by age (±5 yr), race, and county of residence. The response rate was 69% for cases and 56% for controls. Subjects with the following diseases or conditions were excluded from the study: a history of cancer (other than nonmelanoma skin cancer), uncontrolled cardiovascular diseases, hepatic dysfunction (defined as serum bilirubin >1.5 mg/dl, aspartate aminotransferase >40 units/l, and alkaline phosphtase >140 units/l), and renal dysfunction (defined as blood urea nitrogen >20 mg/dl and serum creatinine >1.8 mg/dl). The study protocol was approved by the appropriate institutional review boards. After informed consent from participants was obtained, an in-person, structured interview was conducted at the home of participants or any other place of their preference. Questions were asked regarding demographics, family history of cancer, occupational history, physical activity, use of tobacco and alcohol, and usual dietary habits. Diet was assessed by the Block 1987 Food Frequency Questionnaire that covered 66 items of food or food groups.

cessed within 2 h of collection. Separated plasma specimens were aliquoted into 0.5 ml straws of a sealed capillary tube straw system (Cryo BioSystems, Paris, France) and stored in liquid nitrogen tanks at –196◦ C until analysis. Concentrations of α-carotene, β-carotene, βcryptoxanthin, lycopene, and lutein/zeaxanthin in plasma samples were measured by a method described by El-Sohemy et al. (25) at the Biomarker Analysis and Lipoprotein Research Laboratories in the Department of Nutrition, Harvard School of Public Health. Plasma samples (250 µl) were mixed with 250 µl ethanol containing 10 µg/ml rac-Tocopherol (Tocol) as an internal standard, extracted with 4 ml hexane, evaporated to dryness under nitrogen, and reconstituted in 100 µl ethanol-dioxane (1:1 vol/vol) and 150 µl acetonitrile. Samples were quantitated by high-performance liquid chromatography on a Restek Ultra C18 150 mm X 4.6 mm column, 3 µm particle size encased in a water bath to prevent temperature fluctuations and equipped with a trident guard cartridge system (Restek, Corp., Bellefonte, PA). A mixture of acetonitrile, tetrahydrofuran, methanol, and a 1% ammonium acetate solution (68:22:7:3) was used as mobile phase at a flow rate of 1.1 ml/min, with a Hitachi L-7100 pump in isocratic mode, an L-4250 UV/Vis (445 nm) detector, and a programmable AS-4000 autosampler with water-chilled tray interfaced with a D-6000 interface module. The system manager software (D-7000, version 3.0) was used for peak integration and data acquisition (Hitachi, San Jose, CA). The minimum detection limits in plasma (µg/l) were 7.74 for α-carotene, 7.31 for β-carotene, 5.51 for β-cryptoxanthin, 8.49 for lycopene, and 6.31 for lutein/zeaxanthin. Because lutein and zeaxanthin co-elute on the chromatogram, the 2 were grouped and provided as lutein/zeaxanthin. The between-run coefficients of variation (CV) for α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin were under approximately 5% in plasma. The within-run CVs for these 5 carotenoids were 2.1% or lower. Internal quality control was monitored with 4 control samples analyzed within each run. These samples consisted of 2 identical high-level plasmas and 2 identical low-level plasmas. Comparison of data from these samples allowed withinrun and between-run variation estimates. In addition, external quality control was monitored by participation in the standardization program for carotenoid analysis from the U.S. National Institute of Standards and Technology. During the entire course of measurements, laboratory technicians were blinded to case-control status of plasma specimens.

Statistical Analysis

Measurement of Plasma Carotenoids At the end of the interview, a 30-ml blood sample was drawn in tubes containing citric acid. Blood samples were packed on ice and delivered to the CAVHCS hospital and proVol. 59, No. 1

Differences in plasma concentrations of carotenoids between cases and controls were evaluated by Student’s t-test. Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer in relation to plasma carotenoids were estimated by unconditional logistic regression analysis. Plasma levels of each of the carotenoids examined were divided 47

Table 1. Characteristics of Cases and Controls in a Population-Based Case-Control Study of Prostate Cancer in Arkansas, 1998–2003a Characteristic Age (yr) Mean (SD) Race (%) White African American BMI (kg/m2 ) Mean (SD) Education (%) Some high school or lower High school graduate or some college College graduate or higher Smoking (%) Never smokers Ever smokers

Cases (n = 193)

Controls (n = 197)

64.4 (9.0)

59.4 (10.5)

53.4 46.6 28.1 (4.6)

48.2 51.8 29.0 (5.7)

33.7 48.7

18.8 55.3

17.6

25.9

31.6 68.4

35.0 65.0

a: Abbreviation is as follows: BMI, body mass index.

into quartiles. The risk of prostate cancer for subjects in 3 upper quartiles of a carotenoid was compared with the risk of those in the lowest quartile. In the initial regression models, the following confounders were included: age, race, body mass index [weight (kg)/height (m2 )], education, and smoking (never and ever). Also included were interactions terms between age, race, and smoking status and each of plasma carotenoids (classified in quartiles). The statistical significance of each of the interaction terms constructed was evaluated by the likelihood ratio test. Because none of the interaction terms examined was statistically significant, they were removed from the multivariate models. To assess the independent effect of each of the 5 carotenoids considered on prostate cancer risk, the models fitted for each single carotenoid were further adjusted for the other 4 carotenoids. Stratified analysis by Gleason score ( 0.05). As it is not feasible and practical to determine prostatic concentrations of carotenoids in large epidemiological studies, this comparison study suggests that it is more etiologically relevant to link plasma levels of carotenoids, rather than their dietary intake, to prostate cancer risk. Although circulating concentrations of carotenoids have this methodological advantage over dietary intake of these natural antioxidants, only 3 case-control studies (29–31) and 6 cohort or nested case-control studies (26,32–36) have investigated the effect of plasma/serum levels of carotenoids on the risk of prostate cancer (Table 4). All of these studies were conducted in the United States except 1 study measuring 50

plasma total carotene only in Basel, Switzerland (33). The populations examined in these studies were predominantly of European origin and thus even scarcer data were available for African Americans, a population with the highest incidence rate of prostate cancer in the world. The inverse relation between plasma levels of β-cryptoxanthin and lycopene and prostate cancer risk were observed in 4 (26,29,30,35) of the 8 studies (26,29–32,34–36), which was consistent with the results of this study. The influence of plasma concentrations of lutein/zeaxanthin, α-carotene, and β-carotene on prostate cancer were mixed in these studies (26,29–32,34–36). As in this study, plasma carotene, especially β-carotene, appeared to increase the risk of prostate cancer in studies carried out in 3 U.S. states (30), Hawaii (32), and Maryland (34). This study has several strengths in comparison with studies summarized in Table 4. Plasma specimens in our study were stored in aliquots of 0.5 ml at –196◦ C, which eliminated the potential adverse influence of repeated freezing and thawing of plasma samples on the accuracy of the measurements of plasma carotenoids. Approximately equal numbers of the Whites and African Americans selected made it possible for us to explore whether the association between plasma carotenoids and prostate cancer differed by race. No appreciable difference in risk estimates was noted between Whites and African Americans in this study. Of all studies using serum or plasma data (26,29–36), the risk of prostate cancer in relation to plasma or serum carotenoids was compared between Whites and African Americans only in a casecontrol study conducted in Atlanta, Detroit, and 10 counties in New Jersey (30). In the multicenter study (30), high serum β-carotene significantly increased prostate cancer risk among African Americans, but this detrimental effect was not evident among Whites. More studies are warranted to investigate whether differences in circulating concentrations of various carotenoids among ethnic groups may partially account for the excessive risk of prostate cancer in African Americans. Data are scarce on whether the relation between plasma carotenoids and prostate cancer risk is modified by the Gleason score. Our study revealed that the effects of plasma lycopene, lutein/zeaxanthin, α-carotene, and β-carotene on the risk of prostate cancer were more pronounced for highgrade (more aggressive) tumors. Several lines of experimental evidence suggest that oxidative stress is implicated in prostate carcinogenesis. It has been found that expression of 3 major antioxidant enzymes— manganese superoxide dismutase, catalase, and glutathione peroxidase—were reduced in prostatic adenocarcinoma as compared with normal prostatic tissue or benign prostatic hyperplasia (37–39). It was also reported that prostate cancer cell lines were defective in repairing oxidative DNA base lesions (40). In addition to antioxidant properties, carotenoids may be involved in the regulation of cellular signaling, differentiation, proliferation, and apoptosis (34). A recent study showed that lycopene inhibited the growth of human prostate cancer cells in vitro and in nude mice (41). Collectively, these experimental data have established biological plausibility for our observation that plasma levels of lutein/zeaxanthin, Nutrition and Cancer 2007

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450/450

CLUE I: 182/364 CLUE II: 142/284 205/483

1.26 (0.70–2.26) 0.68 (0.35–1.32) 0.86 (0.48–1.52)c 0.78 (0.43–1.41) 0.86 (0.48–1.53)

1.10 (0.73–1.65)

Lutein: 1.0 (0.5–2.0) Zeaxanthin: 1.5 (0.7–2.9) –

0.32 (0.15–0.69)

Lutein: 0.30 (0.09–1.03) Zeaxanthin: 0.22 (0.06–0.83) 1.51 (P > 0.05)

Lutein/zeaxanthin

0.68 (0.38–1.20)

1.25 (0.65–2.38) 0.90 (0.48–1.70) 0.81 (0.46–1.43)

0.80 (0.57–1.11)

0.48 (0.26–0.89)

0.83 (0.46–1.48) 0.79 (0.41–1.54) 1.04 (0.61–1.77)

0.75 (0.54–1.06)



1.1 (0.5–2.2)

1.8 (0.9–3.9)



1.30 (0.63–2.71)

0.65 (P > 0.05)

0.17 (0.04–0.78)

Lycopene

0.48 (0.23–1.02)

0.98 (P > 0.05)

0.31 (0.08–1.24)

β-cryptoxanthin

OR/RRb (95% CI)

1.6 (0.8–3.5)

0.46 (0.21–0.98)

1.64 (P > 0.05)

0.43 (0.13–1.49)

β-carotene

0.63 (0.36–1.12)

0.93 (0.49–1.78) 1.11 (0.52–2.36) 1.18 (0.68–2.05)

0.77 (0.54–1.10)

0.77 (0.43–1.36)

0.94 (0.50–1.77) 1.47 (0.74–2.92) 0.85 (0.49–1.49)



Total carotene: 0.81 (0.34–1.94)

1.2 (0.5–2.5)

0.33 (0.16–0.72)

1.24 (P > 0.05)

0.26 (0.07–1.05)

α-carotene

a: Abbreviations are as follows: OR, odds ratio; RR, relative risk; CI, confidence interval; MSKCC, Memorial Sloan-Kettering Cancer Center; CLUE, Give us a CLUE to cancer; CARET, β-Carotene and Retinol Efficacy Trial. b: OR/RRs shown were for the highest versus lowest category. Confounders adjusted differed among the studies shown and no confounders were adjusted in the study reported by Nomura et al. (32). c: Data shown at the high and low rows were for lutein and zeaxanthin, respectively.

Wu et al. 2004 (35)

Goodman et al. 2003 (36)

Huang et al. 2003 (34)

Physicians’ health study Washington County, Maryland CARET, 6 centers in United States Health professionals follow up study

Gann et al. 1999 (26)

290/2,974 men followed 578/1,294

142/6,860 men followed

Japanese Americans in Hawaii

Basel, Switzerland

118/52

Eichholzer et al. 1999 (33)

Chang et al. 2005 (31) Cohort or nested case-control studies Nomura et al. 1997 (32)

209/228

65/132

Cases/Controls or Cohort Size

Atlanta, Detroit, 10 NJ counties Houston, Texas

MSKCC, New York

Case-control studies Lu et al. 2001 (29)

Vogt et al. 2002 (30)

Population

Author, Year (Reference No.)

Table 4. Summary of Studies of the Relation Between Circulating Levels of Carotenoids and Risk of Prostate Cancera

β-cryptoxanthin, and lycopene were inversely associated with prostate cancer risk. The elevated risk of prostate cancer with high plasma levels of α-carotene and β-carotene in this study have also been found in some other studies (30,32). Similarly, β-carotene supplement use increased lung cancer risk among smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study in Finland (42) and the Beta-Carotene and Retinol Efficacy Trial in the United States (43). Therefore, biological mechanisms for the effect of carotenes on carcinogenesis may be complex and merit further investigation. Several limitations in this study are worthy of consideration. The nature of case-control approach precluded us from making causal inferences on the relation between carotenoids and prostate cancer. It is likely that changes in diet among some subjects after diagnosis of prostate cancer might have somewhat influenced their plasma carotenoid levels and, in turn, the results of our study. Like other case-control studies in this area, our study had a relatively small sample size, which gave us limited statistical power to detect any modest associations. Approximately 50% of the cases and controls included in this study were African Americans due to the oversampling of this ethnic group from the main study. Therefore, caution should be exercised when the results of this study are extrapolated to the general population. Plasma concentrations of carotenoids were determined 3 to 8 yr after plasma samples were collected and stored at –196◦ C. However, a study conducted in Washington County, Maryland (44) revealed that serum levels of β-carotene, α-tocopherol, and retinol were stable for at least 15 yr of storage at— 70◦ C. Carotenoids are transported in the blood exclusively by lipoproteins, and thus plasma concentrations of lipoproteins may influence the bioavailability of carotenoids (45). Because plasma specimens were obtained from a larger study, finite availability of plasma samples did not allow us to measure plasma lipids in this study. It is possible that failure to adjust for plasma levels of lipids might have confounded our results to some extent. Adjustment for plasma cholesterol in some studies (26,30), however, has not resulted in any appreciable changes in risk estimates. The calculations of dietary intake of carotenoids are ongoing, and the availability of such data will permit a more comprehensive evaluation of the relation between carotenoids and prostate cancer. In summary, plasma lycopene was significantly associated with a reduced risk of prostate cancer among AfricanAmerican and White men in Arkansas. This protective effect was also apparent for plasma lutein/zeaxanthin and β-cryptoxanthin, whereas an adverse effect was detected for plasma α-carotene and β-carotene. However, it should be pointed out that the associations of lutein/zeaxanthin, βcryptoxanthin, α-carotene, and β-carotene with prostate cancer risk were not statistically significant. In view of sparse data on plasma carotenoids and prostate cancer, more studies need to be conducted among populations with different dietary habits and genetic susceptibility to further investigate the role of dietary intake and circulating levels of carotenoids in the etiology and prevention of this malignancy. Future 52

epidemiological studies are encouraged to collect data on both dietary carotenoids and their biochemical indicators and to evaluate whether carotenoids interact with molecular variants in genes related to oxidative stress and oxidative defense to modulate the risk of prostate cancer. Acknowledgments and Notes This study is supported by grants from the Centers for Disease Control and Prevention through the Arkansas Comprehensive Cancer Control Program (Dr. Zhang, Principle Investigator) and from the National Institute on Aging, National Institute of Health (1R01AG15722, Dr. Lang, Principle Investigator). We thank Michele Whitworth for her technical assistance during the implementation of this study. Address correspondence to Jianjun Zhang, M.D., Ph.D., Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 820, Little Rock, AR 72205. Phone: 501–526–6687. FAX: 501–686–5845. E-mail: [email protected]. Submitted 21 November 2006; accepted in final form 30 March 2007.

References 1. American Cancer Society. Cancer Facts & Figures. Atlanta, GA: American Cancer Society, 2006. 2. Parkins DM, Whelan SL, Ferlay J, Teppo L, and Thomas DB. Cancer Incidence in Five Continents: IARC Scientific Publications No. 155. Lyon, France: International Agency for Research on Cancer, 2002. 3. Zhang J, Suzuki S, and Sasaki R: Cancer incidence among native Chinese and Chinese residing in Hong Kong, Singapore and the United States. J Aichi Med Univ Assoc 23, 427–436, 1995. 4. Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, et al.: Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 63, 963–966, 1991. 5. Hsing AW, Devesa SS, Jin F, and Gao YT: Rising incidence of prostate cancer in Shanghai, China. Cancer Epidemiol Biomarkers Prev 7, 83– 84, 1998. 6. Park SK, Sakoda LC, Kang D, Chokkalingam AP, Lee E, et al.: Rising prostate cancer rates in South Korea. Prostate 66, 1285–1291, 2006. 7. Dagnelie PC, Schuurman AG, Goldbohm RA, and Van den Brandt PA: Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies. BJU Int 93, 1139–1150, 2004. 8. Chan JM, Gann PH, and Giovannucci EL: Role of diet in prostate cancer development and progression. J Clin Oncol 23, 8152–8160, 2005. 9. Sonn GA, Aronson W, and Litwin MS: Impact of diet on prostate cancer: a review. Prostate Cancer Prostatic Dis 8, 304–310, 2005. 10. Zhang J and Kesteloot H: Milk consumption in relation to incidence of prostate, breast, colon, and rectal cancers: is there an independent effect? Nutr Cancer 53, 65–72, 2005. 11. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, and Willett WC: A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev 12, 1403–1409, 2003. 12. Brody T: Nutritional Biochemistry. San Diego, CA: Academic Press, 1999. 13. Sesso HD: Carotenoids and cardiovascular disease: what research gaps remain? Curr Opin Lipidol 17, 11–16, 2006. 14. Zhang J, Munger RG, West NA, Cutler DR, Wengreen HJ, et al.: Antioxidant intake and risk of osteoporotic hip fracture in Utah: an effect modified by smoking status. Am J Epidemiol 163, 9–17, 2006. 15. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, and Willett WC: A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 94, 391–398, 2002. 16. Kirsh VA, Mayne ST, Peters U, Chatterjee N, Leitzmann MF, et al.: A prospective study of lycopene and tomato product intake and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 15, 92–98, 2006.

Nutrition and Cancer 2007

17. Etminan M, Takkouche B, and Caamano-Isorna F: The role of tomato products and lycopene in the prevention of prostate cancer: a metaanalysis of observational studies. Cancer Epidemiol Biomarkers Prev 13, 340–345, 2004. 18. Ohno Y, Yoshida O, Oishi K, Okada K, Yamabe H, et al.: Dietary beta-carotene and cancer of the prostate: a case-control study in Kyoto, Japan. Cancer Res 48, 1331–1336, 1988. 19. Daviglus ML, Dyer AR, Persky V, Chavez N, Drum M, et al.: Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study. Epidemiology 7, 472–477, 1996. 20. Norrish AE, Jackson RT, Sharpe SJ, and Skeaff CM: Prostate cancer and dietary carotenoids. Am J Epidemiol 151, 119–123, 2000. 21. Schuurman AG, Goldbohm RA, Brants HA, and van den Brandt PA: A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 13, 573–582, 2002. 22. Willett WC: Nutritional Epidemiology. New York: Oxford University Press, 1998. 23. Stone A, Ratnasinghe LD, Emerson GL, Modali R, Lehman T, et al.: CYP3A43 Pro(340)Ala polymorphism and prostate cancer risk in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 14, 1257–1261, 2005. 24. Nowell S, Ratnasinghe DL, Ambrosone CB, Williams S, TeagueRoss T, et al.: Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 13, 270–276, 2004. 25. El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, et al.: Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. Am J Clin Nutr 76, 172–179, 2002. 26. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, et al.: Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 59, 1225–1230, 1999. 27. Clinton SK, Emenhiser C, Schwartz SJ, Bostwick DG, Williams AW, et al.: Cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev 5, 823–833, 1996. 28. Freeman VL, Meydani M, Yong S, Pyle J, Wan Y, et al.: Prostatic levels of tocopherols, carotenoids, and retinol in relation to plasma levels and self-reported usual dietary intake. Am J Epidemiol 151, 109–118, 2000. 29. Lu QY, Hung JC, Heber D, Go VL, Reuter VE, et al.: F. Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Cancer Epidemiol Biomarkers Prev 10, 749–756, 2001. 30. Vogt, T M, Mayne ST, Graubard BI, Swanson CA, Sowell AL, et al.: Serum lycopene, other serum carotenoids, and risk of prostate cancer in U.S. Blacks and Whites. Am J Epidemiol 155, 1023–1032, 2002. 31. Chang S, Erdman JW Jr., Clinton SK, Vadiveloo M, Strom SS, et al.: Relationship between plasma carotenoids and prostate cancer. Nutr Cancer 53, 127–134, 2005. 32. Nomura AM, Stemmermann GN, Lee J, and Craft NE: Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev 6, 487–491, 1997.

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33. Eichholzer M, Stahelin HB, Ludin E, and Bernasconi F: Smoking, plasma vitamins C, E, retinol, and carotene, and fatal prostate cancer: seventeen-year follow-up of the prospective basel study. Prostate 38, 189–198, 1999. 34. Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, et al.: Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. Am J Epidemiol 157, 335–344, 2003. 35. Wu K, Erdman JW Jr, Schwartz SJ, Platz EA, Leitzmann M, et al.: Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 13, 260–269, 2004. 36. Goodman GE, Schaffer S, Omenn GS, Chen C, and King I: The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 12, 518–526, 2003. 37. Bostwick DG, Alexander EE, Singh R, Shan A, Qian J, et al.: Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer 89, 123–134, 2000. 38. Baker AM, Oberley LW, and Cohen MB: Expression of antioxidant enzymes in human prostatic adenocarcinoma. Prostate 32, 229–233, 1997. 39. Zachara BA, Szewczyk-Golec K, Tyloch J, Wolski Z, Szylberg T, et al.: Blood and tissue selenium concentrations and glutathione peroxidase activities in patients with prostate cancer and benign prostate hyperplasia. Neoplasma 52, 248–254, 2005. 40. Trzeciak AR, Nyaga SG, Jaruga P, Lohani A, Dizdaroglu M, et al.: Cellular repair of oxidatively induced DNA base lesions is defective in prostate cancer cell lines, PC-3 and DU-145. Carcinogenesis 25, 1359–1370, 2004. 41. Tang L, Jin T, Zeng X, and Wang JS: Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. J Nutr 135, 287–290, 2005. 42. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group: The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers: The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 330, 1029–1035, 1994. 43. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, et al.: The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 96, 1743–1750, 2004. 44. Comstock GW, Alberg AJ, and Helzlsouer KJ: Reported effects of long-term freezer storage on concentrations of retinol, beta-carotene, and alpha-tocopherol in serum or plasma summarized. Clin Chem 39, 1075–1078, 1993. 45. Parker RS: Absorption, metabolism, and transport of carotenoids. FASEB J 10, 542–551, 1996.

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