Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population

PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.     

睾酮5-α还原酶Ⅱ基因V89L多态性与前列腺癌预后关系的研究

目的:探讨睾酮5-α还原酶Ⅱ(SRD5A2)基因V89L多态性与影响前列腺癌预后因素的关系。方法:对V89L多态性位点用Rsa-1限制性内切酶进行酶切鉴定,观察112例前列腺癌患者和89例BPH患者的V89L(VV、VL、LL)多态性分布情况的差异及其多态性与前列腺癌患者年龄、前列腺特异性抗原(PSA)、游离PSA/总PSA值(tPSA/fPSA,F/T)、Gleason评分、临床分期的关系。结果:前列腺癌组112例与BPH组89例的V89L基因频度风险无显著性差异(χ2=3.606,df=2,P=0.165)。前列腺癌组VV和VL+LL基因型与fPSA、tPSA、F/T、T分期、Gleason评分差异无显著性(P>0.05)。VV和VL+LL各评价预后指标差异无显著性(P>0.05)。分段评价PSA水平、Gleason评分、临床分期、年龄,均与两种基因型无相关性(P>0.05)。结论:V89L多态性与预后无明显关系,但是可能与前列腺癌的风险存在间接的关系。     

Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer

The prostate gland is an androgen-dependent, and polymorphisms in androgen synthesis gene steroid 5-alpha reductase type II (SRD5A2) may be associated with benign prostatic hyperplasia (BPH) and prostate cancer. We evaluated the association between 3 polymorphisms in the SRD5A2 gene (2 single nucleotide polymorphism: alanine-49 to threonine [A49T] and valine-89 to leucine [V89L], and a (TA)n dinucleotide repeat in the 3' untranslated region), and BPH and prostate cancer within a multiethnic population. Men between 60 and 86 years of age were recruited from annual prostate cancer screening programs and from a large urology clinic. Unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (95% CI). We genotyped 606 men (412 Hispanic, 98 Caucasian, 73 African-American, and 23 Asian), of whom 100 had prostate cancer, 393 had BPH (280 symptomatic and 113 asymptomatic), and 113 had normal prostates. Overall, the V89L variant was associated with prostate cancer; the OR for men with the leucine-leucine (LL) genotype compared to men with the valine-valine (VV) genotype was 4.47 (95% CI, 1.24-16.18). This association was stronger in Hispanics (OR=7.26; 95% CI: 1.49-35.47). Although V89L was nonsignificantly associated with BPH in overall population, BPH risk increased significantly with the number of L alleles in Hispanics (P for trend=0.03). Prostate cancer and BPH were not associated with the alanine-49 to threonine single nucleotide polymorphism and the (TA)n repeat. These results suggest that the SRD5A2 gene may play an important role in both BPH and prostate cancer.     

SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness

BACKGROUND: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.     

Polymorphisms in the 5alpha reductase type 2 gene and urologic measures of BPH

BACKGROUND: The objective of the study was to examine associations between SRD5A2 polymorphisms and measures of benign prostatic hyperplasia (BPH). METHODS: Participants were 510 Caucasian men (median age 60 years), randomly selected from the Olmsted County, MN community to participate in a longitudinal study of BPH. From 1990 through 2000, biennial measurements of lower urinary tract symptom severity (assessed from the American Urological Association Symptom Index, AUASI), peak urinary flow rates (Qmax), and prostate volume were made. Genotyping of SRD5A2 V89L, A49T, and TA repeat polymorphisms were performed. RESULTS: Compared with the VV genotype, the LL genotype was associated with an enlarged prostate (Hazard ratio (HR)=1.62, 95% confidence interval (CI)=1.06, 2.43) but not with AUASI, Qmax, or PSA. The A49T and TA repeat polymorphisms were not associated with BPH. When the LL/VL, AT/TT, and TA0/TA0 genotypes were considered high risk, the number of high risk genotypes increased with increasing prostate volume (32.3, 30.7, 34.1, and 38.7, respectively, P for trend=0.04). CONCLUSIONS: These findings do not demonstrate consistent associations between SRD5A2 genotypes and BPH. However, they suggest that the associations of V89L polymorphisms and prostate volume should be investigated further.     

Association of prostate cancer risk and aggressiveness to androgen pathway genes: SRD5A2, CYP17, and the AR

BACKGROUND: The prostate is an androgen-regulated organ and polymorphisms in genes involved in testosterone synthesis, in particular, SRD5A2 (A49T and V89L variants), CYP17 (MspAI variant), and the AR (CAG, GGC repeats), represent candidate risk factors for prostate cancer incidence and aggressiveness. METHODS: We evaluated the relationship between these five polymorphisms and prostate cancer risk in a family-based case-control study (N = 920). Cases were diagnosed at major medical institutions in Cleveland Ohio, and Detroit Michigan, and their unaffected brothers were used as controls. Associations were investigated with regard to prostate cancer risk, and clinical characteristics at diagnosis (i.e., tumor stage/grade, age, family history). RESULTS: The SRD5A2 V89L variant was associated with an increased risk of prostate cancer (OR = 1.56, P = 0.02). This association was driven primarily by men diagnosed at an earlier age (OR = 2.35, P = 0.001), or with more aggressive disease (OR = 1.63, P = 0.06). None of the other variants exhibited noteworthy associations with disease. CONCLUSIONS: These findings suggest that the SRD5A2 V89L variant may influence risk of developing prostate cancer, especially among men with a younger age of diagnosis or more aggressive disease.     

Association of polymorphisms within androgen receptor, 5alpha-reductase,and PSA genes with prostate volume,clinical parameters,and endocrine status in elderly men

BACKGROUND: The aim of this study was to assess the impact of polymorphisms of three genes within the androgen pathway on prostate volume, clinical parameters, and endocrine status. METHODS: Elderly men with lower urinary tract symptoms underwent clinical and endocrine work-up. In parallel, polymorphisms within the 5alpha-reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR; number of CAG repeats), and the prostate specific antigen (PSA) gene (A --> G substitution at position-158) were determined by polymerase chain reaction and restriction-length polymorphism analysis by using DNA from peripheral blood. RESULTS: A total of 190 men (66.5 +/- 9.2 yr) were analyzed. The number of CAG repeats within the AR and the PSA polymorphism revealed no associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had larger prostates (54.1 vs. 39.3 ml), higher PSA levels (12.2 vs. 4.3 ng/ml), and a 35% reduction in prostatic stroma/epithelial cell ratio. Men with the mutated SRD5A2 V89L gene had lower testosterone levels. CONCLUSIONS: In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of importance for benign prostatic hyperplasia. Polymorphisms within the 5alpha-reductase gene are interesting biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement.     

Preoperative serum prostate specific antigen does not reflect biochemical failure rates after radical prostatectomy in men with large volume cancers

PURPOSE: We compared pathological findings with prostate specific antigen (PSA) failure rates following radical prostatectomy for large volume cancers (6 cc or greater). MATERIALS AND METHODS: A total of 191 men whose radical prostatectomy specimen had a cancer volume of 6 cc or greater were followed for a mean of 3.6 years (range 0.3 to 11.1) and 112 (58.6%) had PSA failure (PSA 0.07 ng./ml. or greater and increasing). Percent Gleason grade 4/5 (the Stanford modified Gleason scale), cancer volume, seminal vesicle invasion, regional lymph nodes, capsular penetration, positive surgical margin, location of the largest cancer in the peripheral or transition zone, prostate weight, patient age, preoperative PSA and clinical stage were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: In univariate regression analysis percent Gleason grade 4/5, lymph node involvement, cancer volume, cancer location in the peripheral zone, capsular penetration and positive surgical margins were significant predictors of biochemical failure. Seminal vesicle invasion, preoperative serum PSA, patient age, prostate weight and clinical stage were not statistically significant. Forward stepwise, multivariate analysis showed that percent Gleason grade 4/5 (p <0.0001, relative risk ratio 2.498), cancer location in the peripheral zone (p = 0.0097, 1.887), cancer volume (p = 0.0157, 1.691) and lymph node involvement (p = 0.0317, 1. 666) were the only independent predictors of biochemical failure. When 52 men with organ confined, large volume prostate cancer were analyzed separately, univariate and multivariate analyses showed that only cancer location in the peripheral zone (p = 0.0021, relative risk ratio 13.473) and percent Gleason grade 4/5 (p = 0. 0449, 4.111) were independent predictors of failure. CONCLUSIONS: Percent Gleason grade 4/5, cancer location in the peripheral zone, cancer volume and lymph node involvement have prognostic value in large volume prostate cancer. Cancer location in the peripheral zone and percent Gleason grade 4/5 are the most powerful predictors of biochemical failure in men whose cancer is 6 cc or greater and contained in the prostatic capsule. Preoperative serum PSA is not helpful in distinguishing biochemical failure rates in these large volume cancers whether they are organ confined or not.     

Pretreatment predictors of time to cancer specific death after prostate specific antigen failure

PURPOSE: Whether pretreatment factors that predict for time to prostate specific antigen (PSA) failure also predict for time to prostate cancer specific death after PSA failure for patients with competing causes of mortality treated during the PSA era was the subject of this study. MATERIALS AND METHODS: Of 415 men with a median age of 73 years who underwent external beam radiation therapy between 1988 and 2001 for clinically localized prostate cancer 160 (39%) experienced PSA failure and 96 (23%) died. In 46 men (48%) the cause of death was prostate cancer. Cox regression multivariable analyses (multivariable analysis) were performed to evaluate the ability of the pretreatment PSA and centrally reviewed biopsy Gleason score to predict time to prostate cancer specific death after PSA failure. RESULTS: When analyzed as categorical variables using multivariable analysis, biopsy Gleason score 4 + 3 (p = 0.02), 8 to 10 (p = 0.02) disease and a pretreatment PSA greater than 20 ng./ml. (p = 0.03) were significant predictors of time to prostate cancer specific death after PSA failure. Estimates of prostate cancer specific death 5 years after PSA failure were 24%, 40% and 59% (p = 0.01) for patients with a biopsy Gleason score < or = 6, 3 + 4, 4 + 3 or higher and 22%, 40% and 60% (p = 0.04) for patients with a pretreatment PSA of 10 or less, greater than 10 and 20 or less, or greater than 20 ng./ml., respectively. CONCLUSIONS: Patients at high risk for PSA failure after radiation therapy based on pretreatment PSA greater than 20 ng./ml. or biopsy Gleason score 4 + 3 or greater are also at high risk for death from prostate cancer after PSA failure despite competing causes of mortality.     

Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer

BACKGROUND: The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS: Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS: Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS: Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.     

Percent Gleason grade 4/5 as prognostic factor in prostate cancer diagnosed at transurethral resection

PURPOSE: We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. MATERIALS AND METHODS: A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. RESULTS: At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. CONCLUSIONS: Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.     

类固醇5a-还原酶Ⅱ基因89位点多态性与亚洲男性前列腺癌易感性的Meta分析

目的 探讨类固醇5a-还原酶Ⅱ (SRD5a2)基因89位点多态性与亚洲男性前列腺癌易感性的关系。方法 检索PubMed、中国知网、万方、维普数据库,获取SRD5a2基因89位点多态性与亚洲男性前列腺癌易感性的病例-对照研究。以前列腺癌组与对照组人群基因型分布的OR值为效应指标,采用固定或随机效应模型进行合并分析,并进...     

Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy

BACKGROUND: Vitamin D has been linked with prostate cancer risk in epidemiologic studies and has antiproliferative, prodifferentiation, and antimetastatic properties in experimental systems. Its hormonal activity is mediated by the vitamin D receptor. We investigated whether germ-line genetic variation in the vitamin D receptor impacts progression of prostate cancer after radical prostatectomy. METHODS: We analyzed BsmI and TaqI polymorphisms using archived specimens from a large series of radical prostatectomy patients at a single institution. Our series included 428 white men (WM) and 310 African-American men (AAM) who were carefully and uniformly staged and followed for 5-10 years. RESULTS: The distribution of polymorphisms varied between WM and AAM. There was little association between genotype and extent of disease at diagnosis, Gleason score, preoperative PSA, or recurrence overall. Among WM with locally advanced disease, however, the BsmI B allele protected against recurrence in models examining gene dose (P = 0.04) and dominant effects (P = 0.05). CONCLUSIONS: Overall vitamin D receptor polymorphisms did not predict pathologic features of prostate cancer but may impact on risk of recurrence among men in certain risk groups. Analysis of polymorphisms may provide clues about the mechanisms through which vitamin D exerts its inhibitory effects on prostate cancer in vivo in men.     

Prognostic features in men who died of prostate cancer

PURPOSE: Since the advent of widespread prostate specific antigen (PSA) based screening in the United States, the risk of over diagnosis as well as delayed diagnosis due to existing PSA thresholds has become a concern. Treatment decision planning is generally linked to prognostic variables, most notably PSA, clinical stage and Gleason grade. We examined these and other prognostic variables in a cohort of men who ultimately died of prostate cancer. MATERIALS AND METHODS: Of 413 men with prostate cancer in a cohort in San Antonio, Texas between 1993 and 2003 who died of disease we identified 211 who died as a direct result of prostate cancer. In these cases we assessed presenting symptoms, PSA history, tumor stage and Gleason score at diagnosis. RESULTS: Of the 211 men 141 (67%) underwent screening for prostate cancer prior to diagnosis. Of 190 men with PSA data at diagnosis available 7 (3.7%) had PSA less than 4.0 ng/ml and 27 (14%) had PSA 4.0 to 10.0 ng/ml. Clinical stage distribution was cT1 in 21.1% of cases, cT2 in 50.7% and cT3 in 26.8%. Of 167 men for whom biopsy Gleason grade was available 16.8%, 16.2%, 24% and 43.1% had Gleason sum 5 or less, 6, 7 and 8 or higher, respectively. CONCLUSIONS: While most men who ultimately die of prostate cancer have poor prognostic features, a substantial number have features associated with a potentially good prognosis, including low PSA and low Gleason grade. Many men who died of prostate cancer had undergone prior screening. These data demonstrate the need for improved markers of prognosis and continued assessment of the efficacy of screening with PSA.     

Percentages of positive cores, cancer length and Gleason grade 4/5 cancer in systematic sextant biopsy are all predictive of adverse pathology and biochemical failure after radical prostatectomy

AIM: We investigated whether the quantitative parameters of systematic sextant biopsies were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy (RP). METHODS: We retrospectively evaluated a total of 117 men with untreated prostate cancer whose needle biopsies were matched with RP specimens. The pretreatment parameters of the serum prostate-specific antigen (PSA), the PSA density, the percentage of positive biopsy cores, the percentage of cancer length and the percentage of Gleason grade 4/5 cancer in the biopsy were determined and compared with the pathological features of prostate cancer in RP specimens. These pretreatment parameters and pathological factors in the RP specimens, including the cancer volume, the percentage of Gleason grade 4/5 cancer, the positive surgical margin and the seminal vesicle invasion were evaluated for their ability to predict the disease recurrence. RESULTS: The percentages of positive biopsy cores, the Gleason grade 4/5 cancer in the biopsy and the cancer length in the biopsy had a weak correlation with the cancer volume in RP specimens (r = 0.373, 0.345, 0.408, respectively). All quantitative biopsy parameters were strongly predictive of the non-organ-confined status, the positive surgical margin and the seminal vesicle invasion in the logistic regression analysis. The percentage of positive biopsy cores and the percentage of Gleason grade 4/5 cancer in the biopsy predicted biochemical failure after RP. CONCLUSION: These results indicate that quantitative biopsy parameters are independent predictors of the adverse pathology of prostate cancers and disease recurrence after RP.     

Dedifferentiation of prostate cancer grade with time in men followed expectantly for stage T1c disease

PURPOSE: We assess whether the Gleason grade changes in men followed expectantly with clinical stage T1c prostate cancer. MATERIAL AND METHODS: We studied 70 men with stage T1c prostate cancer who underwent watchful waiting with repeat needle biopsy sampling to assess for progression. After the initial cancer diagnosis all men had at least 1 other biopsy demonstrating cancer. RESULTS: Of 70 cases 9 (12.9%) showed a significant change in grade from Gleason scores 6 or less to 7 or greater. The average followup of those patients without a change in grade was 22 months and greater than those with a change in grade. There was no difference between the groups with and without changes in grade in regard to initial prostate specific antigen (PSA), percent-free PSA, or PSA density or velocity. Of 9 cases there were 5 (56%) and 8 (89%) with grade change that occurred at 12 and 15 months or less after initial biopsy, respectively. In contrast, only 1 of 24 (4%) patients in whom last re-biopsy was performed 24 months or greater after the initial cancer diagnosis had a change in grade. Of the 21 men who underwent radical prostatectomy 5 (24%) had worsening of grade on the radical prostatectomy specimen compared to biopsy, with a mean interval of 18 months between the initial cancer diagnosis and prostatectomy. This prevalence of grade change is less than in our population that underwent prostatectomy within 1 to 3 months after biopsy. CONCLUSIONS: Because most grade changes occurred relatively soon after biopsy, it implies that tumor grade did not evolve but rather the higher grade component was not initially sampled. During a 1 1/2 to 2-year period after biopsy there is no evidence that prostate cancer grade worsens significantly. Men with prostate cancer need not feel concerned about waiting several months before undergoing surgery after biopsy. Furthermore, men undergoing watchful waiting can be reassured that there is little evidence that prostate cancer grade worsens during the short term.     

Evidence for a biopsy derived grade artifact among larger prostate glands

PURPOSE: The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. MATERIALS AND METHODS: We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS: Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. CONCLUSIONS: These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.