Prostate Cancer and African-American Men
Prostate Cancer and African-American Men
Dr. Powell has written a comprehensive review of factors believed to contribute to the racial differences observed for prostate cancer incidence and mortality. Prostate cancer has a greater negative impact on African-Americans than on any other racial or ethnic group. However, the etiology of the striking racial variation in prostate cancer incidence and mortality remains enigmatic.
Although it is now accepted that cancer is the result of a series of genetic alterations, prostate carcinogenesis appears to be heavily influenced by environmental factors as well. Moreover, socioeconomic factors contribute significantly to the prostate cancer survival disadvantage experienced by African-American men. Racial differences in prostate cancer incidence and mortality are likely to be due to a complex interplay of genetic and environmental factors. Consequently, defining the etiology of these racial differences will be an imposing task.
Two Important, Unresolved Questions
With regard to race and prostate cancer, two important but separate questions need to be resolved. The incidence of clinically manifest prostate cancer is higher in African-American men than in any other ethnic or racial group. However, the prevalence of candidate prostate cancer precursor lesions (prostatic intraepithelial neoplasia and incidental prostate cancer) is very similar when African-American men are compared to other ethnic and racial groups. This suggests that cancer-initiating events occur with uniform frequency regardless of race, while cancer-promoting events occur more frequently in African-American men.
Alternatively, African-American men may be subjected to peculiar environmental, genetic, or epigenetic events that carry a greater risk for prostate cancer progression. Factors that may explain the observed prostate cancer racial differences include dietary fat content and racial differences in androgen metabolism. In addition, there may be unidentified molecular genetic factors that differentiate prostate cancer in African-Americans from that seen in other racial groups.
Dietary Fat and Prostate Cancer
Numerous studies have examined the relationship between dietary fat intake and prostate cancer. Several animal and in vitro studies have linked dietary fat intake with prostate carcinogenesis.[3-5] Whereas case-control studies commonly demonstrate a link between dietary fat intake and prostate cancer risk,[6,7] cohort studies, which are thought to provide a more direct indication of disease risk, do not consistently establish such a link.[8-11]
There is no clear mechanism linking dietary fat to prostate carcinogenesis. However, as pointed out by Dr. Powell, the large body of evidence implicating dietary fat as an etiologic factor in this disease argues for further study in this area. Moreover, studies showing that dietary fat intake is higher for African-Americans than for other racial groups imply that dietary fat intake may contribute to racial differences in prostate carcinogenesis.
Role of Circulating Androgens
Similar to dietary fat intake, the role that circulating androgens play in prostate carcinogenesis has not been fully elucidated. Nevertheless, a considerable body of evidence points to androgens as possible risk factors for prostate cancer. Prostate cancer is essentially nonexistent in men castrated before puberty. Prolonged androgen stimulation of Noble rats results in the development of tumors in the dorsal lobe of the prostate.[13,14]
Based on this evidence, it has been hypothesized that elevated circulating androgen levels contribute to the development of prostate cancer. Moreover, circulating androgen levels, as well as 5-alpha-reductase levels, are higher in African-American men than in Caucasian and Asian men, suggesting that androgen levels may contribute to the racial differences that have been observed for prostate cancer incidence and progression.[15,16]
Thus, while precise roles have not been determined, both dietary fat intake and hormonal factors should be evaluated further to determine whether or not they can shed light on the racial differences in prostate cancer incidence.
Socioeconomic Factors and Survival
Whether or not striking racial differences exist for prostate cancer survival, stage for stage, is a point of controversy. A number of studies have shown that, stage for stage, African-Americans are at a survival disadvantage.[17,18] However, considerable recent and historical evidence suggests that this is not the case.[19-22] These data support the hypothesis that socioeconomic factors account for the striking racial differences in prostate cancer survival.
Dr. Powell discusses the impact that barriers to health care can have on stage at presentation and subsequent prostate cancer survival. Numerous obstacles, including lack of prostate cancer education, avoidance behaviors, fear and incertitude about major medical centers, and limited medical resources, must be overcome to eliminate the effect of socioeconomic factors on racial differences in prostate cancer survival.
The impact that prostate cancer has on the African-American community is unrivaled in any other racial or ethnic group. Several areas of research must be pursued in order to reduce prostate cancer mortality in the African-American community. The role of diet and hormones in prostate carcinogenesis must be elucidated. Also, the clinical and molecular characteristics that distinguish prostate cancer in African-American men require further investigation.[23-28] The multidisciplinary approach to these problems proposed by Dr. Powell seems to be a prudent, rational road to follow if we are to relieve the burden that prostate cancer represents for the African-American community.
1. Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61:759-767, 1990.
2. Sakr WA, Haas GP, Cassin BF, et al: The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 150:379-385, 1993.
3. Pandalai PK, Pilat MJ, Yamazaki K, et al: Polyunsaturated fatty acid, essential fatty acids, prostate neoplasm, omega-3 fatty acids, omega-6 fatty acids, linoleic acid, linolenic, acid, and eicosapentaenoic acid: The effects of omega-3 and omega-6 fatty acids on in vitro prostate cancer growth. Anticancer Res 16:815-820, 1996.
4. Wang Y, Corr JG, Thaler HT, et al: Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet [see comments]. J Natl Cancer Inst 87:1456-1462, 1995.
5. Kondo Y, Homma Y, Aso Y, et al: Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats. Cancer Res 54:6129-6132, 1994.
6. Whittemore AS, Kolonel LN, Wu AH, et al: Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and asians in the United States and Canada. J Natl Cancer Inst 87:652-661, 1995.
7. West DW, Slattery ML, Robison LM, et al: Adult dietary intake and prostate cancer risk in Utah: A case-control study with special emphasis on aggressive tumors. Cancer Causes Control 2:85-94, 1991.
8. Le Marchand L, Kolonel LN, Wilkens LR, et al: Animal fat consumption and prostate cancer: A prospective study in Hawaii. Epidemiology 5:276-282, 1994.
9. Giovannucci E, Rimm EB, Colditz GA, et al: A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer Inst 85:1571-1579, 1993.
10. Hsing AW, McLaughlin JK, Schuman LM, et al: Diet, tobacco use, and fatal prostate cancer: Results from the Lutheran Brotherhood Cohort Study. Cancer Res 50:6836-6840, 1990.
11. Severson RK, Nomura AM, Grove JS, et al: A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. Cancer Res 49:1857-1860, 1989.
12. Pienta KJ, Esper PS: Risk factors for prostate cancer. Ann Intern Med 118:793-803, 1993.
13. Noble RL: Development of androgen-stimulated transplants of Nb rat carcinoma of the dorsal prostate and their response to sex hormones and tamoxifen. Cancer Res 40:3551-3554, 1980.
14. Noble RL: The development of prostatic adenocarcinoma in Nb rats following prolonged sex hormone administration. Cancer Res 37:1929-1933, 1977.
15. Ross R, Bernstein L, Judd H, et al: Serum testosterone levels in healthy young black and white men. J Natl Cancer Inst 76:45-48, 1986.
16. Ross RK, Bernstein L, Lobo RA, et al: 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 339:887-889, 1992.
17. Moul JW, Douglas TH, McCarthy WF, et al: Black race is an adverse prognostic factor for prostate cancer recurrence following radical prostatectomy in an equal access health care setting. J Urol 155:1667-1673, 1996.
18. Pienta KJ, Demers R, Hoff M, et al: Effect of age and race on the survival of men with prostate cancer in the Metropolitan Detroit tricounty area, 1973 to 1987. Urology 45:93-101, 1995.
19. Brawn PN, Johnson EH, Kuhl DL, et al: Stage at presentation and survival of white and black patients with prostate carcinoma. Cancer 71:2569-2573, 1993.
20. Levine RL, Wilchinsky M: Adenocarcinoma of the prostate: A comparison of the disease in blacks versus whites. J Urol 121:761-762, 1979.
21. Ragland KE, Selvin S, Merrill DW: Black-white differences in stage-specific cancer survival: Analysis of seven selected sites. Am J Epidemiol 133:672-682, 1991.
22. Optenberg SA, Thompson IM, Friedrichs P, et al: Race, treatment, and long-term survival from prostate cancer in an equal-access medical care delivery system. JAMA 274:1599-1605, 1995.
23. Moul JW, Sesterhenn IA, Connelly RR, et al: Prostate-specific antigen values at the time of prostate cancer diagnosis in African-American men. JAMA 274:1277-1281, 1995.
24. Reichardt JK, Makridakis N, Henderson BE, et al: Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk. Cancer Res 55:3973-3975, 1995.
25. Corder EH, Guess HA, Hulka BS, et al: Vitamin D and prostate cancer: A prediagnostic study with stored sera. Cancer Epidemiol Biomarker Prev 2:467-472, 1993.
26. Schwartz GG, Hulka BS: Is vitamin D deficiency a risk factor for prostate cancer? (hypothesis). Anticancer Res 10:1307-1311, 1990.
27. Isaacs WB, Bova GS, Morton RA, et al: Molecular genetics and chromosomal alterations in prostate cancer. Cancer 75:2004-2012, 1995.
28. Morton RA: Racial differences in adenocarcinoma of the prostate in North American men. Urology 44:637-645, 1994.