Cancer and Metastasis Reviews 22: 83–86, 2003.# 2003 Kluwer Academic Publishers. Manufactured in The Netherlands.

Prostate cancer in black and white Americans

Sreekanth Reddy1*, Marc Shapiro1, Ronald Morton, Jr.2 and Otis W. Brawley11Winship Cancer Institute, Emory University, Atlanta, Georgia; 2Department of Urology, Baylor School ofMedicine, Houston, Texas

Key words: prostate cancer, race, genetics, outcomes, hormones

Summary

The prostate cancer incidence and mortality of black Americans is among the highest in the world. Thereasons have not been adequately explained. Similar disparities have been noted for men of sub-Saharanorigin living in Brazil and the Caribbean. Avenues of investigation have assessed racial and ethnicdifferences in diet as well as possible differences in the prevalence of genetics (both polymorphisms andmutations). There are studies to suggest that there are no racial differences in outcome when there is equaltreatment. Several studies show that there are racial differences in patterns of care in the US and it has beenhypothesized that this contributes to some of the racial disparity in survival after diagnosis.

The incidence and morality rates of black andwhite Americans from prostate cancer from 1973to 1998 are shown in Figure 1. It has been notedfor some time that American blacks have thehighest incidence and mortality rates from pros-tate cancer in the world. The reasons why areunclear. Some of the high incidence rates in thelate 1980s and beyond may be due to theavailability of screening in the US. Recently,studies in Jamaica and Brazil have demonstratedincreased incidence among residents of sub-Saharan African origin [1,2]. What is race is thesubject of a number of anthropologic papers. Mostagree that race is not a biologic categorization andit might be more scientific to use the term ‘area ofgeographic origin.’ This is not the subject of thispaper. It is appropriate to say that where gooddata exists people of sub-Saharan African origintend to have higher incidence and higher mortalityfor prostate cancer. Unfortunately, there are nogood registries in sub-Saharan Africa.Some studies have suggested the increased risk

of prostate cancer is due to an environmental

influence. In epidemiologic studies, diets high insaturated fat have been correlated with increasedrisk of prostate cancer and there are studies toshow blacks have higher fat consumption com-pared to whites [3,4]. Circulating hormone levelsare related to dietary fat intake. Studies havesuggested that higher circulating androgen levels,particularly dihydrotestosterone, in some popula-tions may account for those populations havinghigher prostate cancer risk [5,6].There is evidence that some populations have

disparate prostate cancer risk due to differences inandrogenic stimulation. The gene SRD5A2 codesfor 5-alpha-reductase. 5-alpha-reductase catalyzesthe conversion of testosterone to the more potentandrogen dihydrotestosterone. Some polymorph-isms of SRD5A2 are related to higher risk forprostate cancer [7] and poorer prognosis [8]. Theuse of the 5-alpha-reductase inhibitor, finasteride,is the subject of a major prostate cancer preventiontrial.Other studies have suggested a part of the

disparity could be attributed to population differ-

* Corresponding author.

E-mail: kanthi_reddy@hotmail.com

ences in genetic polymorphisms. Racial variationin length of the androgen receptor gene CAGrepeat may contribute a small part of the excessrisk of prostate cancer among African Americanmen. In cohort studies, the cohort black men havea shorter average CAG repeat length 20.1+ 3.5 vs.22.1+ 3.1 for whites ðP ¼ 0.009Þ [9]. A shorterCAG repeat in the gene coding for the androgenreceptor is said to code for a receptor moresensitive to androgenic stimulation.The human prostate cancer 1 or HPC 1 gene has

been localized to chromosome 1 by linkageanalysis. Subsequently a second potential geneHPC 2 was found on the X chromosome. Cloningof HPC 1 and 2 remains a vexing problem as thegene has yet to be cloned and the protein producthas not been identified. To date, there is littleevidence to suggest that HPC 1 or 2 accounts forthe racial difference in prostate cancer incidence ormortality.Deletions of chromosome sequences mapping to

the short arm of chromosome 8 have beenobserved frequently in a variety of human cancers.It has been suggested that the terminal portion ofthe short arm of chromosome 8, 8pter-p23, may bedeleted independently of other portions of 8p inhuman tumors, and that deletion of the 8pter-p23region may be correlated with poor prognosis. Onestudy suggests that the independent deletion of8pter-p23 is differentially associated with diseaserecurrence and poor outcome in American Cau-casian but not African American prostate cancerpatients [10].Caveolin-1 is a structural component of caveo-

lae essential to cholesterol transport and signaltransduction. It suppresses c-myc mediated apop-tosis and is transcriptionally regulated by c-myc. Ithas been found to be overexpressed in mouse andhuman prostate cancer. In a clinical study ofprostate cancer patients, 17% of whites and 39% ofblacks had over expression of caveolin-1 byimmunohistochemistry. This suggests that alteredregulation of apoptosis may be associated withracial differences in prostate cancer susceptibitility[11,12].Genetic differences, particularly polymorhism

and certain mutations have been found to have ahigher prevalence in certain populations due togenetic segregation. Specific BRCA-1 mutationshave been found in Askenawshi Jews, for example,

and traced several hundred years to a small groupof individuals [13]. Similar mutations or poly-morphisms may explain the tendency of men ofAfrican origin to have higher risk of prostatecancer.Soy products, Vitamin D, Vitamin E, and

Selenium have all been suggested as preventativesof prostate cancer. If any of these compounds trulyprevent prostate cancer, differences in intake ofthe compound because of culture (diet) orgeographic availability in food stocks may influ-ence prostate cancer incidence and mortality [14–16].Compared with American whites, the propor-

tion of black Americans presenting with regionaland advanced disease is higher [17]. Higher stagehas been correlated and attributed to lowerliteracy and a larger proportion of black Amer-icans have lower literacy [18]. Within stage, it hasbeen noted that blacks tend to present with higherGleason grade disease [19]. Populations studies dodemonstrate that blacks have a higher mortalityand shorter survival within stage [17].There is, however, controversy when comparing

black outcomes within controlled clinical trialsand within health care systems. Several studieshave demonstrated that black Americans withprostate cancer are less likely to get aggressivetherapy. Rates of radiation therapy and radicalprostatectomy are lower among blacks whencompared to whites even when matched for ageand comorbid disease [20–22]. There are studies toshow that when treatment is similar among racialgroups, outcomes are very similar within stage.Optenberg and colleagues [23] studying benefici-aries of US military hospitals showed survivalamong blacks is similar to that among whites andmay surpass it for high-stage disease. Importantlythis is an equal-access medical care system inwhich there were no stage-specific differences intreatment between black and white prostate cancerpatients. The black and white participants in thisstudy also have high literacy. Young and collea-gues [24] did a retrospective analysis of 607patients treated with definitive radiation therapybetween 1987 and 1995. The patient populationanalyzed included African American, Caucasian,and Asian men with AJCC T1-T3 disease. Race,Gleason score, pretreatment prostate-specific anti-gen levels, stage, and treatment delivery were all

84 Reddy et al.

evaluated. The percent free from PSA failure at 48months for African American, Caucasian, andAsian men were 53%, 59%, and 53%, respectively.There was no difference among the three races orfor any of the pairwise comparisons. Gleasonscore and stage of disease were each independentpredictors of outcome, but race was not associatedwith remaining free from PSA failure.There is the suggestion that blacks with meta-

static disease do not benefit from therapy as well aswhites with metastatic disease in the generalpopulation. In a well-designed assessment ofoutcomes in a Southwest Oncology Group Trialof orchiectomy and flutamide vs. orchiectomyalone in men with metastatic prostate cancer,Thompson and colleagues [25] found that race/ethnicity is a prognostic factor for poor outcome.African American men with metastatic prostatecancer had a statistically significantly worseprognosis than white men that cannot be explainedby the prognostic variables explored in their study.Do identically staged black and white men with

identical treatment have differing prognosis is stillan open question. Roach and colleagues [26] usedunivariate and multivariate analyzes to assess thepossible independent significance of race and otherprognostic factors using Gleason score, serum acidphosphates, and nodal status. For men with localand regional disease, race was not of prognosticsignificance for disease free or overall survival.Eastham and colleagues [27] had similar findingsin a study of radical prostatectomy in T1-T2disease. In the Roach study, for men with moreadvanced disease, T2N1-2 and T3-T4Nx, race wasa prognostic factor by both univariate and multivariate analysis. blacks had shorter survival andtime to distant failure was shorter. A higherproportion of blacks in the advanced diseaseanalysis had higher serum acid phosphates levelscompared to white. These populations likely werenot identically staged at the beginning of the studymeaning even with T stage blacks likely hadgreater burden of disease.In population studies black Americans men tend

to have more comorbid disease when compared towhite American men. The effect of increasedprevalence of diabetes, hypertension and cardio-vascular disease on prostate cancer mortality hasyet to be adequately explored [28]. A number ofscientists in reviewing the literature have suggested

that prostate cancer is a more virulent disease inblacks. While blacks present with more advanceddisease and within stage often have higher gradedisease, there is evidence that equal treatmentyields equal outcome among equal patients withthe same burden of disease. Unfortunately, there isevidence of some over-diagnosis with prostatecancer screening, that is diagnosis leading totreatment and even cure of some men who donot need treatment [29]. In a review of allpublished trials in cancer treatment bearing racialinformation Bach and colleagues showed that aonly a modest cancer-specific survival difference isevident, if at all, between blacks and whites treatedcomparably for similar-stage prostate cancer.Therefore, differences in cancer biology betweenracial groups are unlikely to be responsible for asubstantial portion of the survival discrepancy.Differences in treatment, stage at presentation,and mortality from other diseases should representthe primary targets of research and interventionsdesigned to reduce disparities in prostate canceroutcomes.The take home message for the clinician and

patient is there is likely some benefit of treatmentfor most men, black, white or other, with prostatecancer. Differences in access to care, the quality ofcare received, and the impact of co-morbidconditions explain some of the lower survivalreported for black Americans with prostate cancer.The increased incidence and increased mortality ofblack men compared to white men has not beenadequately explained.

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