Can Dietary Choices Prevent Prostate Cancer?
Can Dietary Choices Prevent Prostate Cancer?
January 2001; Volume 4; 1-5
By E-P. Barrette, MD, FACP
Most physicians and patients have some knowledge of the dietary factors influencing diabetes, hypertension, hypercholesterolemia, and coronary artery disease. Low-salt, low-saturated fat, and high-fiber diets often are recommended in their treatment. Similarly, many cancer patients have sought diet and lifestyle recommendations and are trying to follow them.
But for a man whose father recently has been diagnosed with prostate cancer, and whose grandfather died of the disease, how much reliable information could we provide? What can we say?
History
Prostate cancer is the most common cancer in American men. The lifetime risk of being diagnosed with prostate cancer is 13%, while the lifetime risk of dying from prostate cancer is approximately 4%.1
Autopsy studies of men over 50 years of age who have died of causes unrelated to prostate cancer have found histological evidence of prostate cancer in more than 30% of men. The rate of prostate cancer is six times greater in the United States compared with Japan. When men immigrate from Japan and China to the United States, the incidence of prostate cancer rises in just one generation.2
Diet
Animal studies have shown that lower fat diets will slow the growth of prostate cancer. Compelling epidemiologic evidence suggests increased dietary fat or specific fatty foods are associated with higher rates of prostate cancer. This was seen in 11 of 14 case- control studies, with an odds ratio (OR) = 1.3-3.4, and four of five cohort studies, with a relative risk (RR) = 1.8-2.4.1 A consistent trend of increased prostate cancer death rates is seen with higher dietary fat intake.3
The best evidence suggests the type of dietary fat is important. In a large prospective cohort, red meat fat—not vegetable fat—was associated with an increased risk of prostate cancer (RR = 2.64, 95% confidence interval [CI] 1.21-5.77, P = 0.02).4
Several case-control studies showed a significantly lower risk of prostate cancer with higher intake of vegetables,5 particularly cruciferous vegetables.6
Alcohol intake appears to increase the risk of prostate cancer (> 96 g/wk alcohol, approximately 10 drinks, RR = 3.1, 95% CI 1.5-6.3).7
Vitamin E
No published prospective trials have been designed to study the effect of vitamin E and prostate cancer. However, the alpha-tocopherol, beta-carotene cancer (ATBC) prevention study did report a lower incidence of prostate cancer with vitamin E supplements.8
In ATBC, a double-blind, placebo-controlled trial, 29,133 male Finnish smokers ages 50-69 were randomized to alpha-tocopherol (50 mg/50 IU vitamin E per day) alone, beta-carotene (20 mg/d) alone, both alpha-tocopherol and beta-carotene, or placebo. After five to eight years of follow-up, lung cancer rates were unexpectedly higher with beta-carotene and unchanged with alpha-tocopherol. Surprisingly, fewer cases of prostate cancer were seen with alpha-tocopherol (99 vs. 151 cases, 11.7 vs. 17.8 incidence per 10,000 person-years). A 40% decrease in the incidence of clinical tumors (stages II-IV) was noted. No change in the number of latent tumors was seen. Prostate cancer mortality was 41% lower with alpha-tocopherol.9
In the Physicians’ Health Study, a cohort of 47,780 men, prostate cancer cases were prospectively identified and vitamin E supplement use was measured by biennial surveys over 10 years.10 The study included 1,896 non-stage A1 prostate cancer cases. For the entire cohort, vitamin E supplementation did not provide any protection (RR = 1.14, 95% CI 0.82-1.59). In the subgroup of smokers, at least 100 IU or more of vitamin E decreased the risk of metastatic or fatal prostate cancer (RR = 0.44, 95% CI 0.18-1.07). Although this result suggested a protective benefit, it did not reach statistical significance.
Selenium
Selenium is a trace element. Selenium levels in foods vary with the soil content. The RDI is 70 mcg.
Selenium is antitumorigenic in animal models. Lower cancer mortality rates have been noted in counties with higher selenium soil levels. Most case-control and cohort studies also have suggested lower rates of cancers with higher prediagnostic selenium serum levels.
Based on these data, investigators conducted a prospective double-blind, placebo-controlled trial, and randomized 1,312 subjects with a history of basal cell or squamous cell skin cancer to either 200 mcg/d selenium or placebo.11 After a mean follow-up of 4.5 years, no reduction was seen in the primary endpoint: new basal and squamous cell skin cancers. After an interim analysis noted fewer total cancers in the treatment arm, researchers added secondary endpoints: total mortality, cancer mortality, and incidence of prostate, lung, and colon cancer.
| Table 1-Selenium intake and cancer incidence | |||||
| Cancer Site |
Selenium Cases |
Placebo Cases |
RR (95% CI) |
P value |
|
| Prostate | 13 | 35 | 0.37 (0.18-0.71) | 0.002 | |
| Lung | 17 | 31 | 0.54 (0.30-0.98) | 0.04 | |
| Colorectal | 8 | 19 | 0.42 (0.18-0.95) | 0.03 | |
| Total cancer | 77 | 119 | 0.63 (0.47-0.85) | 0.001 | |
| Adapted from: Clark LC, et al. Effects of selenium supplementa- tion for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 1996;276:1957. |
|||||
Significantly fewer cases of prostate, lung, colorectal, and total cancers were noted with selenium. (See Table 1.) The decrease in prostate cancers was the most pronounced. In addition, a significant reduction in total cancer mortality was seen with selenium supplements (29 deaths with treatment vs. 57 deaths in control arm, RR = 0.50, 95% CI 0.31-0.80, P = 0.002).
When cases were stratified by baseline plasma selenium levels, only those in the lowest and middle tertile had a significant benefit. (See Table 2.) The benefit appeared greater in men with baseline PSAs of 4 or less (four cases with treatment vs. 16 in controls, RR = 0.26, P = 0.009).12
| Table 2-Baseline selenium levels and prostate cancer cases |
||||
| Selenium (mcg/ml) |
Selenium Cases |
Placebo Cases |
Relative Risk |
P value |
| < 106.4 | 1 | 13 | 0.08 | 0.002 |
| 106.4-121.2 | 4 | 13 | 0.30 | 0.03 |
| > 121.2 | 8 | 9 | 0.85 | 0.75 |
| Total | 13 | 35 | 0.37 | 0.002 |
| Adapted from: Clark LC, et al. Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br J Urol 1998;81:730. |
||||
In the Health Professionals Follow-up Study, a prospective cohort study of men 40-75 years of age followed for eight years, 33,737 subjects provided toenail clippings for selenium analysis.13 These clippings provided prediagnostic selenium levels, which are believed to reflect long-term intake of 26-52 weeks. One hundred eighty-one new cases of advanced prostate cancer (stages C or D) were matched with controls. When cases and controls were analyzed comparing highest to lowest quintiles of selenium levels in toenail clippings, higher levels were associated with lower rates of cancer (adjusted OR = 0.35, 95% CI 0.16-0.78, P for trend 0.03). The baseline concentration of selenium ranged from 0.66 ppm (comparable to Boston soil) to 1.14 ppm (comparable to South Dakota soil). This reflected an estimated daily selenium intake from 86 mcg in the lowest quintile to 159 mcg in the highest.
Lycopene
Lycopene is the most potent antioxidant among the carotenoids, and in most Americans is the major circulating carotenoid (the others are alpha-carotene, lutein, cryptoxanthin, and beta-carotene). Unlike beta-carotene, lycopene cannot be converted to vitamin A. With no known deficiency syndrome, no RDI exists. Lower serum concentrations of beta-carotene have been associated with an unhealthy lifestyle (i.e., increased body mass index, smoking, and alcohol use), while lower levels of lycopene intake have not. This suggests that lycopene may not be a marker for healthy behaviors.
The dietary sources of lycopene are red tomatoes, and to a lesser extent watermelon, apricots, guava, and pink grapefruit. Processed tomato products appear to have increased lycopene bioavailability, either by the process of heating or by the addition of fat, or both, as lycopene is fat-soluble. Important sources of lycopene are pizza, tomato sauce, salsa, and ketchup.
No published trials of lycopene supplements were found. However, increasing evidence appears to link dietary lycopene intake inversely to a lower risk of prostate cancer. The Health Professionals Follow-Up Study measured the intake of beta-carotene, alpha-carotene, lutein, beta-cryptoxanthin, and lycopene through a food-frequency questionnaire.14 Seven hundred seventy-three non-stage A1 prostate cancer cases were identified. Lycopene intake was associated with a lower risk of prostate cancer (adjusted RR = 0.79, 95% CI 0.64-0.99, for high vs. low quintile, P for trend = 0.04). No association with prostate cancer risk was noted with the other four carotenoids. Overall intake of tomatoes, tomato sauce, tomato juice, and pizza was associated with fewer cases of advanced prostate cancer (stages C and D). The RR was 0.65 (95% CI 0.44-0.95) for consumption of greater than 10 vs. less than 1.5 servings per week (P = 0.01).
In the Physicians’ Health Study, 578 cases of prostate cancer were matched with 1,294 controls.15 Plasma samples were tested for five carotenoids, alpha- and gamma-tocopherol, and retinol. Only lycopene was found at lower plasma levels in cases compared to controls (P = 0.04). An inverse association between cases of aggressive prostate cancer (stage C and D) and lycopene levels was seen (OR = 0.56, 95% CI 0.34-0.91, P for trend = 0.05).
In a comprehensive review of all epidemiologic studies relating cancer risks and lycopene, using either serum levels or intake of tomatoes or tomato-based foods, 72 studies were analyzed.16 Fifty-seven studies reported an inverse association between cancer rates and tomato intake or lycopene levels. Thirty-five of these results were statistically significant. Overall, the evidence was strongest for prostate, lung, and stomach cancers.
Adverse Effects
In the ATBC study more episodes of hemorrhagic stroke were seen with those taking alpha-tocopherol than in those not taking alpha-tocopherol. Vitamin E has been reported to have antiplatelet and anticoagulant effects. In a detailed follow-up analysis of strokes in the ATBC study, the incidence and mortality of subarachnoid hemorrhage were higher in the alpha-tocopherol subjects. However, the absolute rates were very low, e.g., 28 subarachnoid hemorrhage deaths in 14,238 taking alpha-tocopherol vs. 10 in 14,281 controls. Alpha-tocopherol also decreased the overall risk of the much more common cerebral infarction by 14% (95% CI -25% to -1%, P = 0.03) and did not affect rates of intracerebral hemorrhage.17 In the Health Professionals Follow-up Study, vitamin E intake and supplementation did not significantly affect hemorrhagic, ischemic, or total stroke rate.18
Selenium toxicity has been reported with intakes of 1,000 mcg and a maximum safe dietary intake of 800 mcg/d has been suggested. Typical symptoms of toxicity include brittle hair, nail changes, and garlic breath. In the Clark study there were slightly more dropouts in the selenium arm (21 vs. 14). Gastrointestinal complaints were the most common.
Conclusion
A diet low in animal fat appears to decrease the risk of prostate cancer. The benefit with vitamin E may be limited to smokers. Vitamin E may increase the risk of subarachnoid hemorrhage. A benefit of selenium was seen in a large RCT, particularly in men with lower serum selenium values at baseline. A large cohort study has seen a similar benefit. Increased lycopene intake and higher serum levels have been associated with lower rates of prostate cancers.
Physicians’ Health Study II currently is studying vitamin E, vitamin C, beta-carotene, and multivitamins for prevention of prostate cancer.19 The results will not be available for years. The NCI is funding a phase I trial of lycopene supplements.
Recommendation
Until further trials with selenium and lycopene are completed, it is reasonable to recommend a vitamin E supplement (100 IU or more), a selenium supplement (200 mcg), and a diet low in red meat and high in lycopene to men at increased risk of prostate cancer. Depending on one’s appetite, two meals per week of pasta with tomato sauce or pizza, adding tomatoes to a daily salad, and snacking once on chips or veggies with salsa likely would provide the 10 servings per week of lycopene.
References
1. Fair WR, et al. Cancer of prostate: A nutritional disease? Urology 1997;50:840-848.
2. Shimizu H, et al. Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County. Br J Cancer 1991;63:963-966.
3. Carroll KK, Khor HT. Dietary fat in relation to tumorigenesis. Prog Biochem Pharmacol 1975;10:308-353.
4. Giovannucci E, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 1993; 85:1571-1579.
5. Jain MG, et al. Plant foods, antioxidants, and prostate cancer risk: Findings from case-control studies in Canada. Nutr Cancer 1999;34:173-184.
6. Cohen JH, et al. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000;92:61-68.
7. Putnam SD, et al. Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men. Ann Epidemiol 2000;10:361-369.
8. 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 1994;330: 1029-1035.
9. Heinonen OP, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst 1998;90:440-446.
10. Chan JM, et al. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 1999;8:893-899.
11. Clark LC, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 1996;276: 1957-1963.
12. Clark LC, et al. Decreased incidence of prostate cancer with selenium supplementation: Results of a double-blind cancer prevention trial. Br J Urol 1998;81: 730-734.
13. Yoshizawa K, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 1998;90:1219-1224.
14. Giovannucci E, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 1995;87:1767-1776.
15. Gann PH, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: Results of a prospective analysis. Cancer Res 1999;59:1225-1230.
16. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: Review of the epidemiologic literature. J Natl Cancer Inst 1999;91:317-331.
17. Leppala JM, et al. Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol 2000;20:230-235.
18. Ascherio A, et al. Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med 1999;130: 963-970.
19. Christen WG, et al. Design of Physicians’ Health Study II—A randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 2000;10:125-34.
January 2001; Volume 4; 1-5
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