Xiaoying Yu

A common variant associated with prostate cancer in European and African populations

With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele −8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 × 10−11). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of ∼8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

Relationship of Prostate-Specific Antigen Velocity to Histologic Findings in a Prostate Cancer Screening Program

OBJECTIVES For prostate cancer screening, the role of prostate-specific antigen (PSA) velocity (PSAV) in conjunction with total PSA is controversial. We evaluated the relationship of PSAV to histologic findings on biopsy and assessed whether PSAV provides independent predictive information. METHODS From a community-based cohort of 25,276 men screened from 1991 to 2001, 1851 underwent a first biopsy for an elevated PSA and nonsuspicious digital rectal examination with a PSAV available from the year before biopsy. We analyzed the association between PSAV and biopsy histology. RESULTS The histologic findings on biopsy were cancer in 468 (25%), prostatic inflammation in 135 (7%), and benign prostate tissue in 1248 (68%). The cancer detection rate was associated with PSAV and, depending on PSAV, ranged from 13% to 36% (P <0.001). Among men with a PSAV less than 0.5 ng/mL per year, the cancer rate ranged from 27% to 36%, at a PSAV of 0.5 to 3.0 ng/mL per year was 24% to 28%, and at a PSAV greater than 3.0 ng/mL per year was 13% to 18%. On multivariable analysis adjusting for age and PSA, PSAV was independently associated with risk of cancer on biopsy (P <0.0005). The rate of prostatic inflammation was directly associated with PSAV (PSAV of 3.0 ng/mL per year or less: 5% to 9%; PSAV greater than 3.0 ng/mL per year: 11% to 13%, P = 0.01). CONCLUSIONS In screened men with an elevated PSA undergoing biopsy, PSAV provides independent predictive information for estimating prostate cancer risk. Modest increases in PSA are associated with an increased risk of cancer, whereas more dramatic PSA rises are associated with a diminishing risk of cancer and higher rate of inflammation.

Preoperative Prostate Specific Antigen Doubling Time is Not a Useful Predictor of Biochemical Progression After Radical Prostatectomy

PURPOSE Postoperative prostate specific antigen doubling time may be used as a surrogate for prostate cancer specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the usefulness of preoperative prostate specific antigen doubling time for the initial prediction of prostatectomy outcomes. MATERIALS AND METHODS Preoperative prostate specific antigen doubling time was calculated in 1,208 men from a large prostate cancer screening study who were treated with radical prostatectomy. We examined the relationship of prostate specific antigen doubling time with tumor features and biochemical progression-free survival. RESULTS Overall prostate specific antigen doubling time was associated with nonorgan confined disease (OR 0.996, 95% CI 0.992-0.999, p = 0.013) but not with biochemical progression (HR 1.000, 95% CI 0.998-1.001, p = 0.66). Using previously published 18 and 36-month thresholds for prostate specific antigen doubling time there was no significant relationship between doubling time and specific adverse pathological features or biochemical progression. Using the concordance index prostate specific antigen doubling time did not enhance the prediction of biochemical progression beyond that achieved by a model with prostate specific antigen, clinical stage and biopsy Gleason score. CONCLUSIONS In our series of men with newly diagnosed, clinically localized prostate cancer shorter preoperative prostate specific antigen doubling time was associated with nonorgan confined disease but not with biochemical progression after radical prostatectomy. All calculations of prostate specific antigen kinetics may not be equivalent. Caution should be exercised when using prostate specific antigen doubling time in the pretreatment setting.