Erratum: Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment.

Androgen Receptor (AR) signaling is critically important during the development and progression of prostate cancer (PCa). The AR signaling is also important in the development of castrate resistant prostate cancer (CRPC) where AR is functional even after androgen deprivation therapy (ADT); however, little is known regarding the transcriptional and functional regulation of AR in PCa. Moreover, treatment options for primary PCa for preventing the occurrence of CRPC is limited; therefore, novel strategy for direct inactivation of AR is urgently needed. In this study, we found loss of miR-34a, which targets AR, in PCa tissue specimens, especially in patients with higher Gleason grade tumors, consistent with increased expression of AR. Forced over-expression of miR-34a in PCa cell lines led to decreased expression of AR and prostate specific antigen (PSA) as well as the expression of Notch-1, another important target of miR-34a. Most importantly, BR-DIM intervention in PCa patients prior to radical prostatectomy showed reexpression of miR-34a, which was consistent with decreased expression of AR, PSA and Notch-1 in PCa tissue specimens. Moreover, BR-DIM intervention led to nuclear exclusion both in PCa cell lines and in tumor tissues. PCa cells treated with BR-DIM and 5-aza-dC resulted in the demethylation of miR-34a promoter concomitant with inhibition of AR and PSA expression in LNCaP and C4-2B cells. These results suggest, for the first time, epigenetic silencing of miR-34a in PCa, which could be reversed by BR-DIM treatment and, thus BR-DIM could be useful for the inactivation of AR in the treatment of PCa.[This corrects the article on p. 14 in vol. 4.].

Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men.

OBJECTIVE: To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group. DESIGN: Blood aliquots were pooled for each decile of intake of two carotenoids and alpha tocopherol as measured by FFQ. These pooled samples were analyzed for nutrient content, and the resultant blood levels were plotted against the median for each decile of intake. In addition, adipose tissue samples taken from each man were analyzed for content of specific fatty acids. We calculated the Spearman correlations comparing intakes of specific fatty acids as percent of total fat intake, adjusted for energy intake, as measured by FFQ, with the percentage of the corresponding fatty acid in adipose tissue. SUBJECTS AND SETTINGS: African-American men (N=104) with prostate cancer were recruited from a Detroit physician's practice and completed a detailed FFQ. RESULTS: Comparing decile 10 with decile 1 intake of nutrients as measured by FFQ, there was a 32% higher blood level of lycopene, a 288% higher blood level of beta carotene and a 100% higher blood level of alpha tocopherol. The Spearman correlation coefficients between intakes of linoleic acid, alpha linolenic acid, long-chain n-3 fatty acids and trans fatty acid measured by FFQ and the corresponding adipose tissue levels were between 0.10 and 0.47. CONCLUSION: The FFQ was able to distinguish meaningful differences in biochemical measurements of selected nutrients and presumably corresponding differences in the extremes of intake in African-American men with prostate cancer who were likely to be motivated to report accurately. However, the results found are similar to those found in other populations.

Discrimination of dairy industry isolates of the Lactobacillus casei group.

Lactobacilli are a major part of the microflora of the gut and of many fermented dairy products, and are found in a variety of environments. Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, and Lactobacillus zeae form a closely related taxonomic group within the facultatively heterofermentative lactobacilli. The classification and nomenclature of these bacteria are controversial. In this study, relationships between these species were investigated using type strains and dairy industry isolates examined with DNA-based techniques and conventional carbohydrate use tests. Carbohydrate use patterns gave poor discrimination of some species, but DNA PCR using specific primers targeted to sequences of the 16S rRNA gene discriminated 4 types consistent with the currently recognized species. Pulsed-field agarose gel electrophoresis of chromosomal NotI restriction fragments identified 18 different band patterns from 21 independent Lactobacillus isolates and confirmed the identity of L. casei strains from 2 culture collections (CSCC 5203 and ASCC 290), both representing the type strain of L. casei. Some isolates were reclassified as L. rhamnosus, suggesting that the prevalence of L. rhamnosus as a natural component of the microflora of dairy foods and dairy environments has previously been underestimated. These methods can provide a practical basis for discrimination of the species and identification of individual industrial strains.

A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history.

BACKGROUND: The EphB2 gene was recently implicated as a prostate cancer (PC) tumour suppressor gene, with somatic inactivating mutations occurring in approximately 10% of sporadic tumours. We evaluated the contribution of EphB2 to inherited PC susceptibility in African Americans (AA) by screening the gene for germline polymorphisms. METHODS: Direct sequencing of the coding region of EphB2 was performed on 72 probands from the African American Hereditary Prostate Cancer Study (AAHPC). A case-control association analysis was then carried out using the AAHPC probands and an additional 183 cases of sporadic PC compared with 329 healthy AA male controls. In addition, we performed an ancestry adjusted association study where we adjusted for individual ancestry among all subjects, in order to rule out a spurious association due to population stratification. RESULTS: Ten coding sequence variants were identified, including the K1019X (3055A-->T) nonsense mutation which was present in 15.3% of the AAHPC probands but only 1.7% of 231 European American (EA) control samples. We observed that the 3055A-->T mutation significantly increased risk for prostate cancer over twofold (Fisher's two sided test, p = 0.003). The T allele was significantly more common among AAHPC probands (15.3%) than among healthy AA male controls (5.2%) (odds ratio 3.31; 95% confidence interval 1.5 to 7.4; p = 0.008). The ancestry adjusted analyses confirmed the association. CONCLUSIONS: Our data show that the K1019X mutation in the EphB2 gene differs in frequency between AA and EA, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA.

Reduction of QM protein expression correlates with tumor grade in prostatic adenocarcinoma.

The QM protein is a transcription cofactor inhibiting the activity of AP-1 transcription factors and is also a ribosomal protein participating in protein synthesis. While protein synthesis is known to be increased in many cancers, inhibition of AP-1 activity presumably suppresses development and growth of sex-hormone-regulated tumor cells. The present study is the first report on immunohistochemical data of QM in human prostatic tissues. Paraffin sections of human prostate cancer samples were immunohistochemically stained for QM. The staining scores were analyzed with the clinicopathologic data of the patients. QM protein expression was found in all normal prostate glands adjacent to prostate cancer and in various intraepithelial neoplasia (PIN). In prostate cancer, the staining intensity and stained areas were decreased, compared to the normal glands and PIN lesions; in high-grade tumors only some patches of tumor cells showed positivity. Intense (3+) staining was mostly observed in the Gleason grade three areas (48%) compared to grade 4 and 5 areas (22%), although both low and high-grade tumors showed similar percentages of weakly stained areas. Moreover, staining in prostatic adenocarcinoma was often topographically patchy and varied from negative or weak (1+) to intense (3+). There was an inverse correlation from normal to low-grade tumors and then to high-grade tumors. However, in high-grade tumors, the positive areas were mostly confined to peripheral aspects of tumors and were particularly strong in foci of perineural invasion. This preliminary study suggests that decreased QM expression may be associated with early development of prostate cancer, but later a high level of QM may facilitate progression of the tumors to a more aggressive phenotype.

Clinical characteristics of African-American men with hereditary prostate cancer: the AAHPC Study.

INTRODUCTION: The African-American Hereditary Prostate Cancer (AAHPC) Study was designed to recruit African-American families fulfilling very stringent criteria of four or more members diagnosed with prostate cancer at a combined age at diagnosis of 65 years or less. This report describes the clinical characteristics of a sample of affected AAHPC family members. METHODS: In all, 92 African-American families were recruited into the study between 1998 and 2002. Complete clinical data including age and PSA at diagnosis, number of affected per family, stage, grade, and primary treatment were available on 154 affected males. Nonparametric Wilcoxon two-sample tests and Fisher's exact test (two-tailed), were performed to compare families with 4-6 and >6 affected males with respect to clinical characteristics. RESULTS: The mean number of affected men per family was 5.5, with a mean age at diagnosis of 61.0 (+/-8.4) years. Age at diagnosis, PSA and Gleason score did not show significant differences between the two groups of families. Based on the Gleason score, 77.2% of affected males had favorable histology. Significantly, there were marked differences between the two groups in the frequency of node-positive disease (P=0.01) and distant metastases (P=0.0001). Radical prostatectomy was the preferred primary therapy for 66.2% of all affected men followed by 20.8% who chose radiation therapy. CONCLUSIONS: Our findings suggest that affected males who carry the highest load of genetic factors are at the highest risk for early dissemination of disease, thus efforts at early diagnosis and aggressive therapeutic approaches may be warranted in these families. Since the primary therapy choices in our study favored definitive treatment (87.0%) when compared to the 1983 and 1995 SEER data in which 28 and 64% received definitive treatment, respectively, it appears that affected African-American men in multiplex families may be demonstrating the reported psycho-social impact of family history on screening practices and treatment decisions for prostate cancer.

High-grade intra-epithelial neoplasia and prostate cancer in Dibombari, Cameroon.

High-grade prostatic intra-epithelial neoplasia (HGPIN) occurs a decade earlier in men of African descent in the US and Brazil, compared to white men. Prostate cancer incidence and mortality is worse in the African-American than in US white men. Sub-Saharan Africa was thought to be a low incidence area. This disparity has been attributed to lifestyle factors such as diet. We report the results of prostatic biopsies, from an ongoing national prostate cancer survey. One hundred and eleven men aged 40 y and over were recruited for medical interview (AUA symptom score), prostate specific antigen (PSA) assay and digital rectal examination (DRE). Between six and 10 cores of random digitally guided needle biopsies were performed on 24 subjects that had either suspicious prostates on digital rectal examination +/ or PSA > or =4 ng/ml. All lesions of the prostate were described on routine histopathology. The Gleason score and proportion of tissue involved with cancer, was determined. Eight men had benign prostatic hyperplasia (BPH), six had cancer, another six had low grade intra-epithelial neoplasia, two had HGPIN, there was one case of BPH and chronic prostatitis and one case of chronic prostatitis only. The cancer patients were aged 58-75 y (mean 66.93 y). Gleason scores ranged from 5 to 9, there was one score of 3. Cancer made up 20-80% tissue samples. HGPIN was found in two cases (mean age 58 y). Significant prostate cancer and the pre-cancerous lesion HGPIN exist in Dibombari, Cameroon. The purported low incidence of prostate cancer may reflect cultural and economic barriers to health care.

Integrated polymerase chain reaction-based procedures for the detection and identification of species and subspecies of the Gram-positive bacterial genus Lactococcus.

AIMS: Five species of the Gram-positive bacterial genus Lactococcus (Lactococcus lactis, L. garvieae, L. plantarum, L. piscium and L. raffinolactis) are currently recognized. The aim of this work was to develop a simple approach for the identification of these species, as well as to differentiate the industrially important dairy subspecies L. lactis subsp. lactis and L. lactis subsp. cremoris. METHODS AND RESULTS: Methods were devised based on specific polymerase chain reaction (PCR) amplifications that exploit differences in the sequences of the 16S ribosomal RNA genes of each species, followed by restriction enzyme cleavage of the PCR products. The techniques developed were used to characterize industrial cheese starter strains of L. lactis and the results were compared with biochemical phenotype and DNA sequence data. CONCLUSIONS: The PCR primers designed can be used simultaneously, providing a simple scheme for screening unknown isolates. Strains of L. lactis show heterogeneity in the 16S ribosomal RNA gene sequence. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides an integrated set of methods for differentiation and identification of lactococcal species associated with agricultural, veterinary, medical and processed food industries.

Trends in falls, poisoning, drowning, and burns Wisconsin: 1986-1996.

Falls, poisoning, drowning, and burns comprise the four most common causes of unintentional injury death not related to motor vehicles. We examine mortality trends for these causes of injury in Wisconsin over a 10-year period (1986-1996). While national age-adjusted rates for fall mortality have remained relatively stable, Wisconsin has experienced a sharp 38% increase. The greatest increase in fall mortality was seen in the aged. Nationally, poisoning mortality rose by approximately 50% during this same period while Wisconsin saw almost no increase in mortality (3%) from poisoning. Wisconsin did experience an increase in deaths from poisoning in middle-aged adults. Mortality from drowning decreased by about 28% both in Wisconsin and in the United States, with much of the progress occurring in children and young adults. Burn mortality also declined nationally and within Wisconsin by 30% to 35%. The Wisconsin Public Health Department's "Healthier People in Wisconsin" objectives for the year 2000 will likely be met for drowning and burns, but not for falls. Overall, unintentional injury mortality in Wisconsin is decreasing. However, specific subpopulations are not reaping the benefits of this decline, suggesting a possible focus for future efforts aimed at lowering unintentional injury mortality.

African American men and hereditary/familial prostate cancer: Intermediate-risk populations for chemoprevention trials.

The risk of prostate cancer diagnosis among African Americans is 66% greater than among European American men. For African Americans with a family history of hereditary prostate cancer the increased risk of diagnosis is even greater. Thus, this population should be a prime target for chemoprevention strategies. In addition to the higher incidence of prostate cancer among African Americans compared with other populations, the mortality of prostate cancer among this high-risk population is significantly greater than 100% compared with other populations, thus further demonstrating the need for chemoprevention in this target population. Autopsy studies and clinical findings support the argument that prostate cancer exhibits more aggressive biological behavior and perhaps more rapid growth among African Americans compared with European Americans. It is hypothesized that genetic and epigenetic factors may be responsible for a more rapid growth rate among African Americans compared with other populations. Accumulating evidence indicates that a diet high in fat content is closely associated with prostate cancer progression. Investigators have reported that fat intake and percentage of energy from fat were highest in African Americans, followed by European Americans, Japanese Americans, and Chinese Americans. In conclusion, African Americans are an important target population to include in chemoprevention trials that include dietary factors as preventive agents.

Biochemical recurrence after radical prostatectomy in black and white American men with a positive or negative family history of prostate cancer.

PURPOSE: We investigated the impact of a family history of prostate cancer on predicting biochemical recurrence in black and white American men. MATERIAL AND METHODS: Between January 1991 and December 1996, 910 men underwent radical retropubic prostatectomy for clinically localized prostate cancer, of whom 676 had data available on prostate cancer family history. Statistical analysis was performed to identify any correlation among the known predictors of biochemical outcome and family history in each race. RESULTS: Median followup was 34 months (range 2 to 103). We identified 355 (52%) and 321 (48%) white and black American men, respectively, for whom data were available on prostate cancer family history, including 177 (26%) with a positive and 499 (74%) with a negative history. Family history was positive in 94 black (29%) and 83 white (23%) men. No significant difference was noted in the incidence of familial prostate cancer in the 2 races (p = 0.10). In black men the biochemical failure rate was 32% and 26% in those with a positive and negative history (log rank test p = 0.51), while in white men the rate was 17% and 18%, respectively (log rank test p = 0.79). A family history positive for prostate cancer was not associated with biochemical failure in either race. CONCLUSIONS: Biochemical recurrence was not significantly worse in patients with a family history of prostate cancer than in those with nonfamilial disease in either race.

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome 1q (HPC1). An even greater proportion of African-American families have shown linkage to HPC1. Therefore, investigators at the National Human Genome Research Institute (NHGRI) in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome Iq (HPC11. An even greater proportion of African-American families have shown linkage to HPC 1. Therefore, investigators at the National Human Genome Research Institute [NHGRI] in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival.

OBJECTIVES: Gleason score 7, in different proportions of grades 3 and 4, is the score most frequently assigned to prostate cancer in our radical prostatectomy specimens (RPSs). We correlated the major grade component of score 7 tumors with clinicopathologic parameters and disease-free survival. METHODS: All Gleason score 7 RPSs were classified as having a major grade of 3 or 4 carcinoma. The two groups were compared according to patient age, race, serum prostate-specific antigen (PSA) level, clinical and pathologic stage, tumor volume, and biochemical recurrence. RESULTS: Of the 534 patients analyzed, 356 and 178 had major grade 3 or 4 tumors, respectively. Compared with patients with 3+4 tumors, those with 4+3 had significantly more advanced clinical and pathologic stages, larger tumor volume, higher preoperative PSA levels, and older age and a higher proportion were African American (P <0.05 for all above parameters). With a mean follow-up of 34.6 months, patients with 3+4 tumors experienced lower rates of PSA recurrence than did those with 4+3 tumors (P = 0.0021). Furthermore, for the subset of patients with organ-confined disease, multivariable analysis that included race, age, clinical stage, preoperative PSA level, tumor volume, and major grade component found only the latter to be a significant predictor of recurrence, with patients who had major grade 4 component tumors experiencing a higher incidence of PSA recurrence than those with major grade 3 tumors (P = 0.012). CONCLUSIONS: The major grade 4 component in Gleason score 7 carcinoma indicates a higher likelihood of biochemical recurrence, particularly for the increasing proportion of patients with organ-confined disease after radical prostatectomy.

Impact of location and multifocality of positive surgical margins on disease-free survival following radical prostatectomy: a comparison between African-American and white men.

OBJECTIVES: Although the rate of positive surgical margins is higher in African-American men (AAM) than in white men (WM), the impact of this difference on survival is not clear. Furthermore, it is unknown whether there are racial differences in the distribution of the positive surgical margins after radical retropubic prostatectomy (RRP). We investigated the differences between AAM and WM in terms of the site and multifocality of the positive surgical margins and their effect on disease-free survival (DFS) following RRP. METHODS: Between January 1991 and December 1995, 493 patients (288 WM and 205 AAM) were treated with RRP as monotherapy. Positive surgical margins were observed in 179 patients (86 WM and 93 AAM). Patients were divided in two groups: group 1 = WM and group 2 = AAM. The incidence and location of the positive surgical margins and their correlation with DFS were determined and compared. RESULTS: Overall, AAM had a higher rate of positive surgical margins than WM (48% versus 33%, respectively, P = 0.001). There was no significant difference in the frequency of multifocality of the positive margins (P = 0.4). Positive surgical margins were located significantly more often at the base in AAM (P = 0.015); however, the location of the positive surgical margins did not impact on DFS between groups. In those with multifocal positive surgical margins, AAM had a worse DFS compared with WM (P = 0.03). CONCLUSIONS: Race is an independent prognostic factor for DFS in patients with positive surgical margins. There were no differences in DFS between WM and AAM based on the margin location. In WM, prognostic factors for DFS in those with positive surgical margins were preoperative serum prostate-specific antigen, Gleason score, and pathologic stage. Conversely, in AAM none of these parameters were significant predictors of failure.

Prostate cancer biochemical recurrence stage for stage is more frequent among African-American than white men with locally advanced but not organ-confined disease.

OBJECTIVES: To determine whether outcome differences between African-American men (AAM) and white men with prostate cancer (PCa) will still be present if we control for stage in a large cohort of men. It is well established that AAM have a worse outcome from PCa than white men. METHODS: We examined 848 consecutive patients who underwent radical prostatectomy at Wayne State University, Karmanos Cancer Institute, between 1991 and 1995. The mean follow-up was 34 months (range 1.5 to 75). We included men with Gleason score 7 (4 + 3) with those men with Gleason score 8 to 10 for racial/ethnic comparisons. RESULTS: AAM and white men diagnosed with organ-confined PCa demonstrated similar prostate-specific antigen (PSA) levels, Gleason grade, and biochemical recurrence. However, AAM diagnosed with non-organ-confined disease demonstrated higher PSA levels and a higher incidence of recurrence than did white men with non-organ-confined disease. There was a trend toward AAM having a greater proportion of high-grade lesions than white men when PCa was not organ confined. The evidence suggests that the difference in recurrence among AAM versus white men is based on pretreatment PSA, grade, extracapsular extension, and positive surgical margins. Seminal vesicle invasion predicted a worse prognosis equally for both AAM and white men. CONCLUSIONS: A difference in biochemical recurrence was not detected between AAM and white men with organ-confined PCa after radical prostatectomy. PSA was higher in AAM than in white men with pathologically locally advanced PCa, and the biochemical recurrence was greater. AAM had a greater percentage of high Gleason grade lesions compared with white men, and this difference approached statistical significance. We hypothesize that AAM have a more rapid growth rate of PCa, which may be responsible for these clinical findings. Further investigations of the biology of PCa are needed to understand these findings.

8pter-p23 deletion is associated with racial differences in prostate cancer outcome.

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798. When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter-p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter-p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter-p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.

Recruitment experience in the first phase of the African American Hereditary Prostate Cancer (AAHPC) study.

The African American Hereditary Prostate Cancer (AAHPC) Study is an ongoing multicenter genetic linkage study organized by Howard University and the National Human Genome Research Institute (NHGRI), with support from the Office for Research on Minority Health and the National Cancer Institute. The goals of the study are to: (i) look for evidence of involvement of chromosome 1q24-25 (HPC1) in African American men with hereditary prostate cancer (HPC) and (ii) conduct a genome-wide search for other loci associated with HPC in African American men. To accomplish these goals, a network has been established including Howard University, the NHGRI, and six Collaborative Recruitment Centers (CRCs). The CRCs are responsible for the identification and enrollment of 100 African American families. To date, 43 families have been enrolled. Recruitment strategies have included mass media campaigns, physician referrals, community health-fairs/prostate cancer screenings, support groups, tumor registries, as well as visits to churches, barber shops, and universities. By far, the most productive recruitment mechanisms have been physician referrals and tumor registries, yielding a total of 35 (81%) families. Approximately 41% (n = 3400) of probands initially contacted by phone or mail expressed interest in participating; the families of 2% of these met the eligibility criteria, and 75% of those families have been enrolled in the study, indicating a 0.5% recruitment yield (ratio of participants to contacts). As the first large-scale genetic linkage study of African Americans, on a common disease, the challenges and successes of the recruitment process for the AAHPC Study should serve to inform future efforts to involve this population in similar studies.

Should the age specific prostate specific antigen cutoff for prostate biopsy be higher for black than for white men older than 50 years?

PURPOSE: Investigators who have examined age specific reference ranges recommend a higher prostate specific antigen (PSA) cutoff for biopsy for black than for white men older than 50 years. We controlled for PSA to determine whether age specific reference range cutoffs for diagnosis defined by the Walter Reed Army Medical Center group (Walter Reed group) would improve the disproportionate prostate cancer prognosis between black and white men. MATERIALS AND METHODS: We studied 651 consecutive patients who underwent radical prostatectomy at Wayne State University between 1991 and 1995 with a mean followup of 34 months (range 1.5 to 75). Log rank tests were used to determine the homogeneity of survival functions between black and white men with similar PSA ranges, and between groups defined by age specific PSA reference ranges for each race. RESULTS: Disease stage and grade were similar or worse in black men for any PSA range, and biochemical disease-free survival was similar or worse within each range. Black men had a higher percentage of high grade prostate cancer than white men 60 to 69 years old who would not have undergone biopsy using the Walter Reed group proposed PSA cutoff. CONCLUSIONS: Black men have similar or worse prostate cancer severity and outcome than white men with similar PSA ranges. Using age specific reference ranges for the PSA test defined by the Walter Reed group, black men have worse outcome than white men after radical prostatectomy. Therefore, we recommend that the PSA cutoff for biopsy should not be higher for black men at any age range.