Serum Lycopene, Other Serum Carotenoids, and Risk of Prostate Cancer in US Blacks and Whites

T. M. Vogt1,2, S. T. Mayne1, B. I. Graubard2, C. A. Swanson2, A. L. Sowell3, J. B. Schoenberg4, G. M. Swanson5, R. S. Greenberg6, R. N. Hoover2, R. B. Hayes2 and R. G. Ziegler2

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
National Center for Environmental Health, Centers for Disease Control and Prevention, Chamblee, GA.
Cancer Epidemiology Services, New Jersey Department of Health and Senior Services, Trenton, NJ.
College of Human Medicine, Michigan State University, East Lansing, MI.
Medical University of South Carolina, Charleston, SC.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986–1989) that included comparable numbers of Black men and White men aged 40–79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites.

Blacks; carotenoids; case-control studies; nutrition; prostatic neoplasms

Abbreviations: CI, confidence interval; NHANES III, Third Health and Nutrition Examination Survey; OR, odds ratio


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality among men living in the United States (1Go). African-American men bear a disproportionately heavy burden from this disease, with incidence rates over 50 percent higher than those for US Whites (1Go). The etiology of prostate cancer and an explanation for the racial disparity in incidence remain elusive. However, migrant studies and temporal shifts in incidence within countries suggest that modifiable factors such as diet could be involved (2GoGo–4Go).

Carotenoids are natural pigments synthesized in plants and bacteria that aid in photosynthesis and photoprotection (5Go). Humans are exposed to these compounds mainly through intake of fruits and vegetables. Although their functional importance is not entirely understood, it is known that some carotenoids are converted to vitamin A in vivo. The cancer-preventive potential of carotenoids has been hypothesized to lie in their ability to quench singlet oxygen and perform antioxidant functions, although other mechanisms have also been suggested (6Go). Although there is evidence that carotenoid-rich foods decrease the risk of many cancers, the literature supporting a protective role for prostate cancer has been inconsistent (7Go). However, several studies have suggested that increased exposure to lycopene, a carotenoid found primarily in tomatoes, may reduce the risk of prostate cancer (8Go).

To explore reasons for the racial disparity in prostate cancer incidence in the United States, the National Cancer Institute conducted a multicenter, population-based case-control study of prostate cancer that included comparable numbers of Black men and White men between the ages of 40 and 79 years. By purposely oversampling Blacks, a population often underrepresented in epidemiologic studies, this design provided a unique opportunity to examine risk patterns among Blacks separately and in comparison with those of Whites. Blood was collected and potential risk factors were assessed in detail by structured at-home interviews. The present analysis investigates the risk of prostate cancer associated with serum concentrations of lycopene and other individual carotenoids, including {alpha}-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Study design
Subjects comprised a subset from a multicenter, population-based case-control study of four cancers, including multiple myeloma and cancers of the prostate, esophagus, and pancreas, that occur excessively in Blacks. Eligible cases were between 40 and 79 years of age with histologically confirmed, incident prostate cancer diagnosed between August 1986 and April 1989. They were identified from records of hospitals covered by the population-based cancer registries for Atlanta, Georgia; Detroit, Michigan; and New Jersey (10 counties). For each study center, cases were selected by a race- and age-stratified sampling scheme that oversampled Blacks and younger men in order to ensure approximately equal numbers of men from each race and across a broad age range. Population-based controls were identified with either random digit dialing (9Go) (under age 65 years) or Health Care Financing Administration records (age 65 years or older) and were frequency matched to the anticipated case distribution by study center, race, and 5-year age group.

After informed consent from participants was obtained, in-person structured interviews were conducted, usually in the subjects' homes. Questions were asked regarding demographics, family history of cancer, medical and sexual history, alcohol and tobacco use, dietary intake, and occupational history. Diet was ascertained via a 60-item food frequency questionnaire in which subjects were asked to recall their usual frequency of consumption of specific foods consumed by US Blacks and Whites (10Go) over their adult lives, excluding the past 5 years.

Study participation
Of the 981 prostate cancer cases and 1,315 controls who were successfully interviewed, a subset was selected to donate blood for further analyses. Cases were considered ineligible if they had undergone orchiectomy or had or were presently undergoing hormone treatment, chemotherapy, or radiation therapy. A total of 483 (234 Black, 249 White) cases were eligible and invited to participate. Of these, blood was successfully obtained from 127 Black cases (54 percent) and 147 White cases (59 percent). Eligible controls were selected to be frequency matched to cases on study center, race, and age. A total of 467 (213 Black, 254 White) controls were invited to participate. Blood was successfully collected from 137 Black controls (64 percent) and 158 White controls (62 percent). For both the interview and blood collection, overall participation rates for eligible subjects were as follows: Black cases, 42 percent; Black controls, 45 percent; White cases, 44 percent; White controls, 42 percent.

Because of budgetary constraints, individual carotenoids were measured in blood from a subset of cases and controls that was balanced by age and race for each study center. These 437 study participants included 209 cases (99 Blacks, 110 Whites) and 228 controls (108 Blacks, 120 Whites).

Biochemical analysis
A phlebotomist visited each participating subject in his home and drew approximately 50 ml of blood. The median interval between prostate cancer diagnosis and blood draw was 3.7 months (ranging from 27 days to 2.3 years). For nutrient analyses, blood was collected in serum separator tubes, previously covered in aluminum foil to limit exposure to natural light. After at least 30 minutes for clot formation, samples were refrigerated. Within 6 hours of blood collection, serum was separated by centrifugation, and 0.5-ml aliquots were stored at -70°C.

In 1991, individual carotenoids (all-trans {alpha}-carotene, all-trans ß-carotene, all-trans ß-cryptoxanthin, lutein/zeaxanthin, all-trans lycopene) were measured in the sera by the Centers for Disease Control and Prevention using isocratic reverse-phase high-performance liquid chromatography with multiwavelength ultraviolet/visible light detection at 450 nm (11Go). After the addition of nonapreno ß-carotene, the internal standard, all samples were extracted into hexane and then redissolved in ethanol, and an equal volume of acetonitrile was added. A filtrate was then injected onto a 15-cm C18 reverse-phase column and eluted with 50 percent ethanol:50 percent acetonitrile containing 100 µl/liter of diethylamine. The chromatograms were quantified by comparing the peak height of each carotenoid with that of the same carotenoid in a standard solution and adjusting for the peak height of the internal standard.

To evaluate quality control, we inserted blinded samples with high and low levels of the individual carotenoids prior to shipment to the Centers for Disease Control and Prevention for analysis. For each of the five carotenoids, the variation in these blinded samples met all of the quality control requirements of Westgard et al. (12Go). Coefficients of variation were between 4 and 8 percent, except the low {alpha}-carotene samples that had a coefficient of variation of 12 percent.

Statistical analysis
Cases and controls were compared in terms of various demographic and other factors using chi-square tests. Among controls, Pearson's correlation coefficients and partial correlation coefficients (adjusted for serum cholesterol) were calculated for serum carotenoids, fruit and vegetable intake, and intake of lycopene-rich foods. The median serum carotenoid concentrations in cases and controls and in Black and White controls were compared using Wilcoxon's rank sum tests.

For both stratified and unstratified analyses, serum carotenoid concentrations were categorized into quartiles based on the total population of controls. Unconditional logistic regression (13Go) was used to generate adjusted odds ratios and 95 percent confidence intervals for prostate cancer risk, with the lowest quartile serving as the referent. To test for linear trend, a variable with values equal to the median among controls for each quartile was treated as continuous and tested in the model. When cases were stratified according to disease aggressiveness, each case group was compared with the controls using polychotomous logistic regression (14Go).

To evaluate confounding, we screened suspected prostate cancer risk factors, as well as other potential confounders identified in the literature. These factors included family history of prostate cancer, personal history of benign prostatic hyperplasia, personal history of vasectomy, daily alcohol consumption, current smoking status, number of cigarettes smoked per day, Quetelet's index, daily energy intake, intake of foods high in animal fat, education, income, ever versus never married, month of blood draw, and serum cholesterol. For each carotenoid, potentially confounding variables were added one at a time to models adjusted only for study design factors. The variable was considered a confounder if, upon addition to the model, all carotenoid odds ratios shifted in a consistent direction and the proportional change for at least one level of exposure exceeded 10 percent. Confounding was further evaluated by using forward and backward modeling in which potentially confounding variables were added/subtracted sequentially. The month of blood draw was the only confounder identified. Therefore, all models were adjusted for the study design factors (age stratified into 10-year categories, race, study center) and month of blood draw stratified into 2-month categories. Interaction was assessed by both examining odds ratios across serum carotenoid levels and statistical significance testing of multiplicative interaction terms.

All statistical tests were two tailed with {alpha} = 0.05. The SAS system (15Go) was used for all analyses except the polychotomous logistic regression modeling for which SUDAAN software (16Go) was used to perform maximum likelihood inference.

Third National Health and Nutrition Examination Survey analyses
To explore differences between US Blacks and Whites, we examined serum lycopene concentrations for 990 Black men and 2,826 White men aged 40–79 years who were participating in the Third Health and Nutrition Examination Survey (NHANES III) (17Go). Individual carotenoids in serum had been analyzed at the Centers for Disease Control and Prevention by high-performance liquid chromatography methods comparable with those used in the present study. Age-specific medians were calculated for men of both races. In addition, a statistical test for racial differences in the mean serum lycopene concentration was performed using analysis of covariance. Age was included as a covariate, and this survey's complex sampling and weighting scheme was taken into account (18Go).


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Of interviewed subjects asked to donate blood, participation was nearly equal by race (59 percent for Blacks and 61 percent for Whites). Subjects were more likely to participate if they were younger, lived in Atlanta versus Detroit or New Jersey, had a positive family history of prostate cancer, earned a higher income, or were more educated, while patterns were not observed for the intake of fruit and vegetables or lycopene-rich foods. Participation by cases versus controls did not vary across categories of these factors in consistent ways (table 1).


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TABLE 1. Participation rates by selected characteristics for interviewed cases and controls asked to donate blood from a US multicenter case-control study, 1986–1989

 
Among the subjects who gave blood, cases were similar to controls by race and, within each race, by study center, month of blood draw, and educational achievement (table 2). However, cases were slightly older than controls, especially among Blacks (p = 0.05).


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TABLE 2. Description by selected characteristics of Black cases and controls and White cases and controls from a US multicenter case-control study, 1986–1989

 
All serum carotenoids were positively and statistically significantly correlated with one another (table 3). Fruit and vegetable intake was positively, but weakly, correlated with each serum carotenoid (all correlation coefficients ~ 0.10) except lycopene (correlation coefficient (r) = -0.02). There was a weak positive correlation between the intake of lycopene-rich foods and serum lycopene (r = 0.12). Adjustment for serum cholesterol altered the correlations very little.


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TABLE 3. Pearson's correlation coefficients (and partial correlation coefficients adjusted for serum cholesterol) for serum carotenoids, fruit and vegetable intake, and intake of lycopene-rich foods among controls from a US multicenter case-control study, 1986–1989

 
The median serum lycopene concentration was lower among cases than controls for both races. In contrast, the concentrations for all other carotenoids were higher among cases compared with controls for both races (table 4). Only the case-control difference among Blacks for lutein/zeaxanthin was statistically significant (p = 0.04).


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TABLE 4. Median serum carotenoid concentrations (10th–90th percentile) for Black cases and controls and White cases and controls from a US multicenter case-control study, 1986–1989

 
Odds ratios by serum carotenoid quartile, as well as test for trend p values, are presented in table 5 for all cases combined and for cases stratified by disease aggressiveness. When all cases were combined, every carotenoid was positively, but nonsignificantly, associated with prostate cancer risk except lycopene, which was inversely associated (test for trend, p = 0.09). Among the carotenoids with positive associations, the strongest effects were observed for ß-carotene and lutein/zeaxanthin. The inverse association with lycopene was particularly apparent among those with aggressive disease (comparing the highest with lowest quartiles, odds ratio (OR) = 0.37, 95 percent confidence interval (CI): 0.15, 0.94; test for trend, p = 0.04). Otherwise, striking differences between nonaggressive and aggressive disease were not observed. Associations were not substantially altered when fully adjusted for all potential confounders; for example, for all cases, the odds ratios by increasing quartile for ß-carotene = 1.00, 1.59, 1.49, and 2.09; the odds ratios by increasing quartile for lycopene = 1.00, 0.90, 0.73, and 0.59. However, adjusting for total carotenoids (excluding lycopene) strengthened the inverse association with lycopene for all cases combined (odds ratios by increasing quartile = 1.00, 0.86, 0.62, and 0.48; test for trend, p = 0.01).


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TABLE 5. Prostate cancer odds ratios for all cases and for nonaggressive and aggressive cases from a US multicenter case-control study, 1986–1989

 
Race-specific models revealed that the association between serum lycopene and the risk of prostate cancer was similar for Blacks and Whites with apparent, although not statistically significant, inverse trends seen for each race (table 6). The positive associations with ß-carotene and lutein/zeaxanthin, though unstable, appeared stronger in Blacks. For other carotenoids, individual odds ratios fluctuated widely, and it was difficult to evaluate differences by race. None of the tests for interaction between race and individual serum carotenoids was statistically significant (data not shown).


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TABLE 6. Prostate cancer odds ratios for Blacks and Whites from a US multicenter case-control study, 1986–1989

 
In a previously published analysis using the full study population of 981 cases and 1,315 controls, the intake of foods high in animal fat was identified as the dietary factor most predictive of prostate cancer risk (20Go). Thus, we decided a posteriori to examine the joint effects on prostate cancer risk of serum lycopene and animal fat intake in the subgroup analyzed for serum carotenoids (table 7). Compared with those with low serum lycopene concentrations and high intake of foods high in animal fat (cutpoints were based on the medians among controls), the odds ratios were statistically significantly decreased for men with high serum lycopene concentrations and low animal fat intake (OR = 0.40, 95 percent CI: 0.22, 0.74). The interaction between these two variables was not statistically significant (p = 0.54), indicating independence of the association of each factor with prostate cancer risk.


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TABLE 7. Joint effects of serum lycopene and intake of foods high in animal fat from a US multicenter case-control study, 1986–1989

 
Effect modification was also evaluated for age (<70 or >=70 years), smoking status (never/past vs. current), and alcohol intake (nondrinkers, 1–20 drinks per week, 21 or more drinks per week) for each individual carotenoid. The associations between exposure and disease did not vary in consistent ways for any of the potential effect modifiers, and none of the interaction terms achieved statistical significance (data not shown).

Because in our study Black controls had a lower median serum lycopene concentration than did White controls (table 4), we sought corroboration in a larger, nationally representative data set. Therefore, the median serum lycopene concentrations for each race were calculated using data from NHANES III (figure 1). In every age group, concentrations for Blacks were lower than those for Whites, with the age-adjusted difference in means achieving statistical significance (p < 0.001).



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FIGURE 1. Median serum lycopene concentrations by age and race among males from the Third National Health and Nutrition Examination Survey, 1988–1994.

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In agreement with a growing body of literature (8Go), our results suggest an inverse association between lycopene and the risk of prostate cancer, a relation which is especially apparent for aggressive disease. Similar findings have been reported in prospective and retrospective studies. In addition, comparable effects have been noted whether lycopene exposure was measured via dietary intake or blood samples. More than 10 years ago, two prospective studies, one assessing tomato intake among California Seventh-day Adventists (21Go) and the other evaluating serum lycopene levels in a cohort of Washington County, Maryland, residents (22Go), noted that higher lycopene concentrations were associated with decreased risk of prostate cancer. Relative risks comparing the highest with lowest quantiles were 0.60 (95 percent CI: 0.37, 0.97) and 0.50 (95 percent CI: 0.20, 1.29), respectively. In 1995, Giovannucci et al. (23Go) reported that the risk of prostate cancer in a cohort of male health professionals was significantly reduced by 35 percent among men with the highest, relative to lowest, intake of tomatoes and tomato-based products. This inverse association was particularly strong among those with more aggressive disease, for whom risk was reduced by over 50 percent. More recently, data from a cohort developed from the Physicians' Health Study demonstrated an inverse relation with baseline levels of serum lycopene, which was also especially strong and statistically significant for cases with aggressive disease (44 percent decrease in risk comparing the highest with lowest quintiles) (19Go). Conversely, a prospective study conducted among Japanese-American men living in Hawaii did not provide evidence for an inverse association with serum lycopene (24Go) nor did a Dutch cohort study assessing tomato intake (25Go). It should be noted, however, that exposure to lycopene in these two study populations was substantially lower than in other studies reporting an inverse association. Several case-control studies also examined this relation with one reporting a statistically significant inverse association with plasma lycopene (26Go). Among case-control studies using dietary estimates of lycopene exposure, some suggested an inverse association with risk (27GoGoGo–30Go), while others found no evidence for an association in either direction (20Go, 31GoGoGoGo–35Go).

Our study included comparable numbers of Black men and White men, thus permitting race-specific analyses and leading to the new finding that higher serum lycopene concentrations are similarly associated with reduced risk of prostate cancer for men of both races. In the analysis of dietary data from our study, there was no evidence of an inverse association between lycopene and the risk of prostate cancer in Black men or White men (20Go). However, commonly consumed sources of lycopene, such as pizza and lasagna, were not included in the questionnaire, and the correlation between intake of lycopene-rich foods and serum lycopene was only 0.12. The only other study to address this association in Blacks and Whites separately was a recent multiethnic case-control study that reported an inverse association between the dietary intake of cooked tomatoes and the risk of prostate cancer in Blacks but not Whites (32Go).

Although our data did not suggest that risk patterns varied by race, the median serum lycopene concentrations were approximately 18 percent lower among Black controls compared with White controls. Similarly, median values for Black men from NHANES III were 12 percent lower than those for White men within the same age range as our controls (19.9 vs. 22.6 µg/dl, respectively). Lycopene intake was also statistically significantly lower among US Blacks compared with Whites in an analysis of the 1987 National Health Interview Survey data (36Go). Given lycopene's potentially protective role, Blacks appear to be at a disadvantage, raising the possibility that differences in lycopene concentrations could contribute to a portion of the racial disparity in prostate cancer incidence. These observations warrant further investigation.

In contrast to our lycopene results, increasing serum concentrations of {alpha}-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin were either unassociated or positively associated with increased risk of prostate cancer. Although not statistically significant, these positive associations were particularly strong for ß-carotene and lutein/zeaxanthin. Similar nonsignificant positive associations have been suggested in other observational studies using serologic data (19Go, 22Go, 24Go).

There is increasing evidence that foods high in fat, especially fat from animal sources, may increase the risk of prostate cancer (20Go, 37Go). The results of the present analysis additionally suggest that the effects of animal fat and lycopene are independent and that the greatest benefit may occur when both animal fat intake is reduced and lycopene intake is increased. It is reassuring that these results are consistent with US Department of Agriculture recommendations suggesting plentiful and varied consumption of fruits and vegetables and reduced intake of high fat meat and dairy products (38Go).

In addition to the inclusion of comparable numbers of Black participants and White participants, our study had several strengths. We estimated carotenoid exposure by measuring blood carotenoid concentrations. In a recent report by Freeman et al. (39Go), individual carotenoids measured in the blood, but not in the diet, were strongly and statistically significantly correlated with prostate tissue levels (for lycopene, r = 0.56 and -0.06 for blood and diet, respectively). Our laboratory reproducibility was excellent with coefficients of variation generally 8 percent or less for blinded quality control materials. The potential for degradation during sample collection and storage seemed minimal because the mean concentrations of serum lycopene, the most labile of the individual carotenoids, were similar in our controls and those in NHANES III (21.18 mg/dl and 22.85 mg/dl, respectively), using race-specific age standardization. In an effort to determine whether the cases included in this analysis were representative of incident prostate cancer across the United States, we compared the distribution of disease characteristics with national cancer statistics collected by the Surveillance, Epidemiology, and End Results Program. For each race, the case distribution by stage was similar to that of the national data. However, a slightly higher proportion of both Black cases and White cases had disease that was well differentiated compared with Surveillance, Epidemiology, and End Results data (data not shown) (40Go, 41Go).

Our results suggest that low concentrations of serum lycopene may be more strongly associated with aggressive prostate cancer. This finding implies that disease progression may be especially susceptible to the protective effects of lycopene. It is also possible that aggressive prostate cancer itself reduced serum lycopene levels. To investigate this possibility, we examined the mean serum lycopene concentrations among cases by disease aggressiveness. Lycopene levels decreased with increasingly aggressive grade and stage (19.6, 16.8, and 15.1 µg/dl for well-differentiated, moderately differentiated, and poorly/undifferentiated disease, respectively, test for trend, p = 0.04; 17.9, 17.0, and 13.7 µg/dl for localized, regional, and distant disease, respectively, test for trend, p = 0.03). However, because this pattern was not observed for any other carotenoid, and because stronger lycopene associations have been observed for aggressive disease in prospective studies (19Go, 23Go), a bias due to disease seems unlikely to explain our findings.

We also considered whether differential participation by cases and controls in the blood collection phase of the study could have distorted our results. Analyses indicated that participation was comparable for cases and controls in terms of race, age, study center, family history of prostate cancer, income, education, intake of fruit and vegetables, and intake of lycopene-rich foods. Thus, we found no evidence that participation bias could account for the findings. Additionally, we considered the possibility that cases could have altered their diet as a result of disease, potentially impacting serum carotenoid levels. In fact, comparable numbers of cases (22 percent) and controls (19 percent) reported major dietary changes in the 6 months prior to blood draw. Excluding these subjects served to modestly strengthen the positive association with ß-carotene, for example (ORs by increasing quartile = 1.00, 1.62, 1.66, and 1.76), but did not substantially alter the results for lycopene (ORs by increasing quartile = 1.00, 0.80, 0.76, and 0.64).

Lycopene is unique among the common carotenoids in that overall fruit and vegetable intake is not a reliable predictor of blood lycopene concentration (42Go). Indeed, in our study the correlation coefficient between serum lycopene and total fruit and vegetable intake was -0.02. Lycopene enters the US diet in the form of tomato-based products (43Go). Absorption and, thus, serum concentrations are enhanced by heat processing and concurrent fat intake (44Go). Items such as spaghetti, lasagna, and pizza, as opposed to fresh tomatoes, may be the dominant sources of lycopene in the United States (45Go). Therefore, we believe that the inverse association between serum lycopene and prostate cancer risk cannot easily be attributed to the increased fruit and vegetable intake typical of "healthy" diets. Furthermore, in a recent validation study, scores from an index of healthy eating were significantly correlated with all plasma carotenoid concentrations with the exception of lycopene (46Go).

A protective role for lycopene in prostate cancer etiology is biologically plausible. Relative to other carotenoids, lycopene has exceptionally high singlet oxygen-quenching ability (47Go). In this way, lipids, nucleic acids, and proteins may be protected from oxidative damage that could otherwise lead to cancer. It is also possible that lycopene, independent of its singlet oxygen-quenching abilities, enhances cellular differentiation, inhibits cell proliferation, maintains intercellular communication, interacts with growth factors, or influences carcinogenesis through other mechanisms (8Go, 48Go, 49Go).

In summary, our findings provide support for the protective role of lycopene in prostate carcinogenesis. Because we included large numbers of US Blacks, these results can now be extended to include this racial subgroup. Although we did not find evidence that the association varied for Black men and White men, it is provocative that racial differences in serum lycopene concentrations were observed, both among our controls and in NHANES III. Thus, differences in lycopene intake or metabolism may contribute to the racial disparity in prostate cancer incidence. We also found that the inverse relation with lycopene was particularly pronounced for aggressive disease. Hypotheses that other individual carotenoids are associated with a reduced risk of prostate cancer were not supported. Our lycopene findings are encouraging because the etiology of prostate cancer, the second leading cause of cancer mortality in US men, remains elusive, with few modifiable strategies.


    ACKNOWLEDGMENTS
 
This study was funded, in part, through National Cancer Institute contracts to the Michigan Cancer Foundation (NO1-CP-5109 and NO1-CN-05225), the New Jersey State Department of Health (NO1-CP-51089 and NO1-CN-31022), the Georgia Center for Cancer Statistics (NO1-CP-51092 and NO1-CN-05227), and Westat, Inc. (NO1-CP-51087).

The authors thank Dr. Joseph L. Gastwirth for his helpful suggestions.


    NOTES
 
Reprint requests to Dr. Tara M. Vogt, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Suite 320, Bethesda, MD 20892 (e-mail: vogtt{at}exchange.nih.gov).


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication May 29, 2001. Accepted for publication September 13, 2001.