African Americans and Prostate Cancer

[odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele.
The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile.
A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively).
When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.

Urol Oncol. 2004 Jan-Feb;22(1):20-4.

Postprostatectomy cancer-free survival of African Americans is similar to non-African Americans after adjustment for baseline cancer severity.

Underwood W 3rd, Wei J, Rubin MA, Montie JE, Resh J, Sanda MG.

Department of Urology, University of Michigan, Ann Arbor, MI, USA.

African American men with localized prostate cancer are less likely than White men to receive a radical prostatectomy. This disparity may exist because African American men have prostate cancers that are more biologically aggressive. We investigated if similar stage cancers of African American men and White men show differences in cancer control after radical prostatectomy. Men with localized prostate cancer who underwent radical prostatectomy during a 6-yr period were stratified by race, and time to prostate-specific antigen recurrence was measured. We used Chi-square and t-tests to compare baseline clinical and pathological factors based on race. Cox proportional hazards model was used to determine effects of race on cancer control while controlling for baseline measures of cancer severity. There were 1,228 cases evaluated. At baseline, African American men were treated at a significantly younger age than White men (P = 0.0027) but showed no significant difference in prostate-specific antigen PSA, Gleason score, pathology stage, maximum tumor dimension, and surgical margin status. Multivariable Cox proportional hazards analysis controlling for cancer severity at prostatectomy revealed that cancer-free survival was not worse among African Americans compared to other subjects (P = 0.16). The responsiveness of prostate cancers among African American men to radical prostatectomy was similar to White men of similar stage and grade. Early detection in African American men may facilitate diagnosis of cancer amenable to prostatectomy. Studies are needed to evaluate the possible interaction of prostate cancer stage and grade shift in African American men and the disease free survival in this population.

Carcinogenesis. 2004 Jan 30

COX-2 gene promoter haplotypes and prostate cancer risk.

Panguluri RC, Long LO, Chen W, Wang S, Coulibaly A, Ukoli F, Jackson A, Weinrich S, Ahaghotu C, Isaacs W, Kittles RA.

National Human Genome Center at Howard University, Washington, DC 20060; National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR.

Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into proinflamatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing.
Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate C/EBPalpha and NF-kb binding sites. A case-control study of the four SNPs in African American (N=288), Bini Nigerian (N=264), and European American (N=184) prostate cancer cases and age matched controls revealed that SNP -297G was associated with decreased risk for prostate cancer (Odds Ratio [OR]=0.49; CI=0.2-0.9; P=0.01). The effect on risk was observed in both African Americans (OR=0.51; CI=0.2-0.9; P=0.01) and European Americans (OR=0.33; CI=0.1-0.9; P=0.02).
In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR=2.72; CI=1.3-5.8; P=0.007 and OR=3.67; CI=1.4-9.9; P=0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations.
Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR=0.4; CI = 0.1-0.9; P=0.02) and European Americans (OR=0.2; CI=0.1-0.9; P=0.03). These data suggests that variation of the COX-2 promoter may influence the risk and development of prostate cancer.

Urology. 2004 Jan;63(1):90-4.

Low AUA symptom score independently predicts positive prostate needle biopsy: results from a racially diverse series of 411 patients.

Porter CR, Kim J.

Section of Urology and Renal Transplantation, Virginia Mason Medical Center, Seattle, Washington 98111, USA.

OBJECTIVES: To evaluate the prebiopsy parameters, including the American Urological Association symptom score (AUASS), that may be predictive of positive biopsy. Transrectal ultrasound (TRUS) biopsy of the prostate represents the reference standard in the diagnosis of prostate cancer. METHODS: A total of 411 consecutive men undergoing TRUS biopsy were prospectively evaluated. The indications for biopsy were abnormal digital rectal examination (DRE) findings and/or an elevated prostate-specific antigen (PSA) level. A single surgeon (C.R.P.) examined all the men. DRE and TRUS were each given a level of suspicion between 1 (low suspicion–smooth DRE, homogeneous TRUS) and 5 (high suspicion–hard DRE, hypoechoic lesion). A level of suspicion of 3 or greater was considered abnormal. The prebiopsy parameters examined included PSA level, age, race, biopsy history, prostate volume, TRUS-detected lesion, and AUASS. RESULTS: Of 411 men, 62% were African American and 38% were white. The mean PSA level was 11.6 ng/mL. The mean patient age was 65.3 years. Overall, 39% of men had abnormal DRE and 32% abnormal TRUS findings. The mean AUASS was 9.3. The positive biopsy rate was 40.8%. Univariate analysis demonstrated that age, PSA level, prostate volume, abnormal DRE findings, TRUS-detected lesion, and AUASS (less than 7, low) were all predictive of a positive biopsy (P <0.05). Race was not statistically significant (P = 0.38). Detailed analysis of the AUASS in the 411 men indicated that 41% had low symptom scores (less than 7), 32% had moderate scores (8 to 19), and 27% had severe scores (20 to 35). In the group of men with low symptom scores (n = 169), univariate analysis demonstrated that age, PSA level, prostate volume, and abnormal TRUS findings were all statistically significant predictors of positive biopsy (P <0.05). Multivariate analysis of the data from the 411 men demonstrated that age, PSA level, prostate volume, abnormal DRE findings, and low AUASS were all independent predictors of positive biopsy (P <0.05). CONCLUSIONS: In this prospective study, the independent predictors of positive TRUS biopsy included age, PSA level, prostate volume, abnormal DRE findings, and low AUASS. A low AUASS may be an important variable to consider when counseling patients before biopsy and when designing patient algorithms for prostate biopsy.

1: Urology. 2004 Jan;63(1):90-4.

Low AUA symptom score independently predicts positive prostate needle biopsy: results from a racially diverse series of 411 patients.

Porter CR, Kim J.

Section of Urology and Renal Transplantation, Virginia Mason Medical Center, Seattle, Washington 98111, USA.

OBJECTIVES: To evaluate the prebiopsy parameters, including the American Urological Association symptom score (AUASS), that may be predictive of positive biopsy. Transrectal ultrasound (TRUS) biopsy of the prostate represents the reference standard in the diagnosis of prostate cancer. METHODS: A total of 411 consecutive men undergoing TRUS biopsy were prospectively evaluated. The indications for biopsy were abnormal digital rectal examination (DRE) findings and/or an elevated prostate-specific antigen (PSA) level. A single surgeon (C.R.P.) examined all the men. DRE and TRUS were each given a level of suspicion between 1 (low suspicion–smooth DRE, homogeneous TRUS) and 5 (high suspicion–hard DRE, hypoechoic lesion). A level of suspicion of 3 or greater was considered abnormal. The prebiopsy parameters examined included PSA level, age, race, biopsy history, prostate volume, TRUS-detected lesion, and AUASS. RESULTS: Of 411 men, 62% were African American and 38% were white. The mean PSA level was 11.6 ng/mL. The mean patient age was 65.3 years. Overall, 39% of men had abnormal DRE and 32% abnormal TRUS findings. The mean AUASS was 9.3. The positive biopsy rate was 40.8%. Univariate analysis demonstrated that age, PSA level, prostate volume, abnormal DRE findings, TRUS-detected lesion, and AUASS (less than 7, low) were all predictive of a positive biopsy (P <0.05). Race was not statistically significant (P = 0.38). Detailed analysis of the AUASS in the 411 men indicated that 41% had low symptom scores (less than 7), 32% had moderate scores (8 to 19), and 27% had severe scores (20 to 35). In the group of men with low symptom scores (n = 169), univariate analysis demonstrated that age, PSA level, prostate volume, and abnormal TRUS findings were all statistically significant predictors of positive biopsy (P <0.05). Multivariate analysis of the data from the 411 men demonstrated that age, PSA level, prostate volume, abnormal DRE findings, and low AUASS were all independent predictors of positive biopsy (P <0.05). CONCLUSIONS: In this prospective study, the independent predictors of positive TRUS biopsy included age, PSA level, prostate volume, abnormal DRE findings, and low AUASS. A low AUASS may be an important variable to consider when counseling patients before biopsy and when designing patient algorithms for prostate biopsy.

: J Sex Marital Ther. 2004 Mar-Apr;30(2):79-93.

Sexuality and health-related quality of life after prostate cancer in african-american and white men treated for localized disease.

Jenkins R, Schover LR, Fouladi RT, Warneke C, Neese L, Klein EA, Zippe C, Kupelian P.

The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

The purpose of this study was to examine differences in sexual attitudes and quality of life of White and African-American men who have undergone radical prostatectomy or radiation therapy for localized prostate cancer. Respondents included 1,112 White and 118 African-American men. Response rates differed by race, with 51% of White men and 28% of African-American men returning the questionnaire assessing demographics, medical history, sexual functioning, attitudes about seeking help for sexual problems, sexual self-schema, and health-related quality of life. African Americans were more likely than Whites to have undergone radiation therapy (p <.0001) and were more likely to indicate that a desire to maintain sexual functioning influenced their treatment choice (p <.0001). African-American men also had more positive attitudes than did White men toward seeking help for sexual problems and were more likely to report seeking past help and intending to seek future help. African-American men reported more problems with sexual desire (p =.0003), although their sexual function scores did not differ significantly from those of Whites. African-American men may be more at risk for distress when prostate cancer treatment causes sexual dysfunction.

Br J Cancer. 2004 Jan 26;90(2):510-4.

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

Brown WM, Lange EM, Chen H, Zheng SL, Chang B, Wiley KE, Isaacs SD, Walsh PC, Isaacs WB, Xu J, Cooney KA.

Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.

African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.

Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):222-7.

Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients.

Caruso RP, Levinson B, Melamed J, Wieczorek R, Taneja S, Polsky D, Chang C, Zeleniuch-Jacquotte A, Salnikow K, Yee H, Costa M, Osman I.

Department of Urology, New York University Cancer Institute, Kaplan Comprehensive Cancer Center, New York, USA.

PURPOSE: The protein encoded by N-myc downstream-regulated gene 1 (NDRG1) is a recently discovered protein whose transcription is induced by androgens and hypoxia. We hypothesized that NDRG1 expression patterns might reveal a biological basis for the disparity of clinical outcome of prostate cancer patients with different ethnic backgrounds. EXPERIMENTAL DESIGN: Patients who underwent radical prostatectomy between 1990 and 2000 at Veterans Administration Medical Center of New York were examined. We studied 223 cases, including 157 African Americans and 66 Caucasians (T2, n = 144; >/=T3, n = 79; Gleason <7, n = 122; >/=7, n = 101). Three patterns of NDRG1 expression were identified in prostate cancer: (a) intense, predominately membranous staining similar to benign prostatic epithelium; (b) intense, nucleocytoplasmic localization; and (c) low or undetectable expression. We then examined the correlations between patients’ clinicopathological parameters and different NDRG1 expression patterns. RESULTS: In this study of patients with equal access to care, African-American ethnic origin was an independent predictor of prostate-specific antigen recurrence (P < 0.05). We also observed a significant correlation between different patterns of NDRG1 expression and ethnic origin. Pattern 2 was less frequent in African Americans (21% versus 38%), whereas the reverse was observed for pattern 3 (60% in African Americans versus 44% in Caucasians; P = 0.03). This association remained significant after controlling for both grade and stage simultaneously (P = 0.02). CONCLUSIONS: Our data suggest that different NDRG1 expression patterns reflect differences in the response of prostatic epithelium to hypoxia and androgens in African-American compared with Caucasian patients. Further studies are needed to determine the contribution of NDRG1 to the disparity in clinical outcome observed between the two groups.

Oncogene. 2004 Jan 15;23(2):605-11.

Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients.

Petrovics G, Zhang W, Makarem M, Street JP, Connelly R, Sun L, Sesterhenn IA, Srikantan V, Moul JW, Srivastava S.

Department of Surgery, Center for Prostate Disease Research, US Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA. gpetrovics@cpdr.org

PCGEM1 is a novel, highly prostate tissue-specific, androgen-regulated gene. Here, we demonstrate that PCGEM1 expression is significantly higher in prostate cancer (CaP) cells of African-American men than in Caucasian-American men (P=0.0002). Further, increased PCGEM1 expression associates with normal prostate epithelial cells of CaP patients with a family history of CaP (P=0.0400). PCGEM1 overexpression in LNCaP and in NIH3T3 cells promotes cell proliferation and a dramatic increase in colony formation, suggesting a biological role of PCGEM1 in cell growth regulation. Taken together, the cell proliferation/colony formation-promoting functions of PCGEM1 and the association of its increased expression with high-risk CaP patients suggest the potential roles of PCGEM1 in CaP onset/progression, especially in these high-risk groups.

1: Mil Med. 2003 Dec;168(12):992-6.

Health practices of male Department of Defense health care beneficiaries: a follow-up on prostate cancer screening in the national capital area.

Boyles G, Moore AD, Edwards QT.

Naval Hospital Guam, Family Practice Clinic, PSC 490 Box 7638, FPO AP 96938-1600.

The purpose of this study was to assess screening for prostate cancer (PC) of male Department of Defense health care beneficiaries in the national capital area. This study was a follow-up of a previous research of African-American men’s PC screening practices. In the previous study, 85% of African-American men screened for PC and the determinants of screening were men’s perceived “benefits” of PC testing, age, and education. This follow-up study was conducted on 234 men age 52 years and over regardless of ethnicity using a questionnaire and convenience sampling similar to the prior study. Results showed 96% screened for PC; no statistical differences in PC screening and ethnicity; and men’s perceived “self-efficacy” and “benefits” were predictors of PC screening. More men screened for PC when advised by their health care providers and 94% of men stated “trust” in health care providers, indicating the importance of a “trusting-informative health care milieu” for men’s self-efficacy to screen for PC.

Urology. 2003 Dec 22;62(6 Suppl 1):3-12.

Epidemiology of prostate cancer.

Crawford ED.

Section of Urologic Oncology, Division of Urology, University of Colorado Health Science Center and the University of Colorado Cancer Center, Denver, Colorado 80262, USA. david.crawford@uchsc.edu

Prostate cancer incidence and mortality rates vary worldwide. In the United States, prostate cancer is the most common malignancy affecting men and is the second-leading cause of cancer death. Risk of developing prostate cancer is associated with advancing age, African American ethnicity, and a positive family history, and may be influenced by diet and other factors. The incidence of prostate cancer increased sharply after the introduction of widespread screening for prostate-specific antigen (PSA), although rates have now returned to levels seen before that time. PSA screening has been associated with a shift toward diagnosis of earlier-stage disease, but this has not been accompanied by a shift toward a lower histologic grade. Although overall prostate cancer mortality rates decreased during the 1990s, it was largely because of reductions in deaths among men diagnosed with distant disease. In contrast, mortality rates for men diagnosed with localized or regional disease increased gradually during most of the 1990s before decreasing slightly among white men and reaching plateaus among African Americans.

Urol Oncol. 2003 Nov-Dec;21(6):483-4.

Trends in prostate cancer mortality among black men and white men in the United States. Chu KC, Tarone RE, Freeman HP, Center to Reduce Cancer Health Disparities, National Cancer Institute, Bethesda, MD. Cancer 2003;97:1507-1516.

Carroll PR.

Prostate cancer mortality rates in the United States declined sharply after 1991 in White men and declined after 1992 in African American men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States.The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among African American men and White men in the United States using the 1969-1999 U.S. prostate cancer mortality rates and the 1975-1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The