E D I T O R I A L

Race, Biochemical DiseaseRecurrence, and Prostate–SpecificAntigen Doubling Time in theSEARCH DatabaseIsaac Powell, MD

Department of Urology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.

I would like to congratulate Hamilton et al. on their attempt to

resolve conflicting data regarding prostate cancer and outcomes

in black compared with white men.1 The most interesting findings

include a significantly younger population of black men with higher

prostate–specific antigen (PSA) levels, similar tumor grade, and less

extracapsular extension. Nevertheless, there is still a higher rate of

biochemical disease recurrence noted in black men compared with

white men. Recent genetic studies have reported that variants on

chromosome 8q24 and CYP3A4 on chromosome 7 are associated

with aggressive prostate cancer in young black men.

The CYP3A4 polymorphism is an A to G single nucleotide poly-

morphism. The G allele increases the amount of active testosterone

available for conversion to DHT and is associated with more aggres-

sive prostate cancer.2 The distribution of AA, AG, and GG alleles is

strongly associated with race (P = .00002), with 92% of white men

having the AA allele compared with 17% of black men. The rates of

homozygous GG allele and heterozygous AG allele are reported to be

1% and 7%, respectively, among white men versus 43% and 39%,

respectively, among black men. We found no significant increase in

the frequency of the G variant among black men by age when com-

paring men age 65 years and age >65 years or by decade of age. We

did note that all black men diagnosed between the ages of 40 and 49

years had at least 1 copy of the G allele. There were no significant

associations noted between genotype and clinical variables grouped

into categories. Likewise, treating age and PSA as continuous variables

and testing their association with genotype using the Jonckheere–

Terpstra rank sum test revealed no significant associations (P values

for age .84 for white men and.63 for black men; P values for PSA .40

for white men and .13 for black men). Disease recurrence occurred at

a fairly constant rate for the first 5 to 7 years after prostatectomy,

with some evidence of a plateau being reached after 7 years of fol-

low–up. Including men of all races and with all stages of disease, men

with the AG and GG allele variants had disease that progressed more

rapidly than men with the AA alleles.3 This may partially explain the

disparity noted in the rate of disease recurrence.

A whole–genome admixture scan in 1597 blacks identified a

3.8 megabase (Mb) interval on chromosome 8q24 as being signifi-

cantly associated with susceptibility to prostate cancer (logarithm of

See referenced original article on pages 2202–9,this issue.

Address for reprints: Isaac J. Powell, MD,Department of Urology, Karmanos Cancer Insti-tute, Wayne State University, 4160 John R, Suite1017, Detroit, MI 48201; Fax: (313) 745-0464.E-mail: ipowell@med.wayne.edu

Received August 14, 2007; accepted August 16,2007.

ª 2007 American Cancer SocietyDOI 10.1002/cncr.23045Published online 12 September 2007 in Wiley InterScience (www.interscience.wiley.com).

2153

odds of 7.1). The increased risk because of African

ancestry is greater in men diagnosed before age 72 years

(P< .00032) and may contribute to the epidemiologic ob-

servation that the higher risk of prostate cancer in blacks

is greatest in younger men.4 This may partially explain

why black men with prostate cancer tended to be 2.1 years

younger than white men in the study by Hamilton et al.1

The interesting finding of a greater proportion of

T1C disease among black men compared with white

men in the study by Hamilton et al.1 may not be

inconsistent with a more aggressive prostate cancer

course noted among black men. There are those

who believe that a diffuse T1C tumor has a worse

prognosis than a T2A tumor because it may be less

nodular and therefore more invasive, but this a hy-

pothesis–driven concept. Although the volume of

disease was not measured in the study by Hamilton

et al.,1 it is possible that the average volume of T1C

disease may have been greater than that of T2A

prostate cancer. These factors also may account for a

greater rate of disease recurrence.

Evidence remains strong that when prostate can-

cer is locally advanced or metastatic, stage for stage,

African heritage is predictive of a poorer outcome.5–7

The majority of this tumor population consists of a

subgroup of the entire spectrum of prostate cancer

and is early in the natural history of the disease. Simi-

lar PSA doubling times among black and white men

with aggressive disease who fail initial therapy would

not be unexpected given the early natural history of

disease in this cohort. The time interval of genetic

expression and phenotypic presentation is unknown

but may be responsible for the increasing disparity

noted in patients with later stages of prostate cancer.

The more important question is why did black men in

the study presented herein have greater rates of bio-

chemical disease recurrence? This question will be

answered both biologically and genetically in the

future and evidence is growing, as demonstrated by

the study by Hamilton et al.1 Most importantly, their

report has demonstrated that early detection and

aggressive treatment can reduce racial disparities.

ConclusionsIf the lessons of other chronic diseases with a high

prevalence in the black community (such as hyperten-

sion and diabetes mellitus) are to be heeded, studies

targeting the screening of black men for prostate can-

cer, along with focused educational efforts regarding the

disease and its risks, should be viewed as a priority

healthcare initiative. Scientific study in the U.S. should

be performed with the goal of reducing racial disparities

in prostate cancer outcome as an endpoint. Although

there is some evidence that racial differences in pat-

terns of care are narrowing, particularly when there is

equal access to healthcare resources, black men con-

tinue to have a higher incidence of prostate cancer,

present at a younger age and with more advanced dis-

ease, and have a poorer prognosis than white men.

Whether this is a biologic phenomenon or reflects dif-

ferences in socioeconomic factors or health–seeking be-

haviors, literacy, cultural beliefs, or environmental/

lifestyle factors has been debated, but a body of evidence

indicates that prostate cancer does have a genetic basis.

Improving the outcome for black men with pros-

tate cancer requires an awareness of the disease’s

epidemiologic patterns and a willingness on the part

of physicians to implement targeted study initiatives

with endpoints designed to detect the disease early in

this population and institute appropriate manage-

ment. In addition, there needs to be more education

regarding prostate cancer and its consequences in the

black community along with improved support initia-

tives, both for patients and their families. However, in

doing so, it should be recognized that there may be

significant barriers. In overcoming these barriers, the

importance of tailored educational programs designed

to help patients gain a better understanding of the

benefits and risks of treatment options and increase

their participation in the management decision–mak-

ing process cannot be overemphasized. With this plan

of action, the reduction of the racial/ethnic outcome

disparities in this disease may be accomplished.

REFERENCES1. Hamilton RJ, Aronson WJ, Presti JC Jr, et al. Race, biochemi-

cal disease recurrence, and prostate–specific doubling time

after radical prostatectomy: results from the SEARCH data-

base. Cancer. 2007:110:2202–9.

2. Rebbeck TR, Jaffe JM, Walker AH, Wein AJ, Malkowicz SB.

Modification of clinical presentation of prostate tumors by

a novel genetic variant in CYP3A4. J Natl Cancer Inst.

1998;90:1225–1229.

3. Powell IP, Zhou J, Sun Y, et al. CYP3A4 genetic variant and

disease–free survival among white and black men after

radical prostatectomy. J Urol. 2004;72(5 pt 1):1848–1852.

4. Freedman ML, Haiman CA, Patterson N, et al. Admixture

mapping identifies 8q24 as a prostate cancer risk locus in

African–American men. Proc Natl Acad Sci U S A. 2006;

103:14068–14073.

5. Powell IP, Dey J, Dudley A, et al. Disease–free survival dif-

ference between African Americans and whites after radical

prostatectomy for local prostate cancer: a multivariable

analysis. Urology. 2002;59:907–912.

6. Powell IP, Banerjee M, Bianco FJ, et al. The effect of race/

ethnicity on prostate cancer treatment outcome is condi-

tional: a review of Wayne State University data. J Urol.

2004;171:1508–1512.

7. Thompson I, Tangen C, Tolcher A, Crawford E, Eisenberger

M, Moinpour C. Association of AAM ethnic background

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2154 CANCER November 15, 2007 / Volume 110 / Number 10