Germline DNA-Repair Genes and HOXB13 Mutations in Korean Men with Metastatic Prostate Cancer: Data from a Large Korean Cohort.

PURPOSE: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. MATERIALS AND METHODS: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. RESULTS: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9-10, 9.9%). CONCLUSIONS: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings.

The establishment of KORCC (KOrean Renal Cell Carcinoma) database.

PURPOSE: The purpose of this article is to report establishment of the 1st Web-based database (DB) system to collect renal cell carcinoma (RCC) data in Korea. MATERIALS AND METHODS: The new Web-based DB system was established to collect basic demographic and clinicopahtological characteristics of a large cohort of patients with RCC in Korea. Data from a total of 6,849 patients were collected from 8 tertiary care hospitals that agreed to participate in organizing the Korean Renal Cell Carcinoma (KORCC) study group as of 1 July 2015. Basic demographic and clinicopathological characteristics were collected. The data of patients who underwent surgical treatments were analyzed to characterize Korean RCC. RESULTS: We established the 1st Web-based DB of Korean RCC, a database comprising renal mass management cases from multiple centers in Korea. The data of 5,281 patients who underwent surgical management (mean follow-up, 32 months) were analyzed. The most common symptom was incidentally detected renal mass (76.9%). Clinical T1a was the most common (54.3%) stage and mean tumor size was 4.8±4.2 cm. Radical nephrectomy accounted for 62.7% of cases and an open approach was used in 50.7% and 52.2% of radical and partial nephrectomies, respectively. The 5-year overall, cancer-specific and recurrence-free survival rates were 88.1%, 92.2%, and 88.0%, respectively. CONCLUSIONS: We report the 1st establishment of a Web-based DB system to collect RCC data in Korea. This DB system will provide a solid basis for the characterization of Korean RCC.

Theracurmin® efficiently inhibits the growth of human prostate and bladder cancer cells via induction of apoptotic cell death and cell cycle arrest.

In the present study, we aimed to investigate the anticancer properties of Theracurmin®, a novel form of the yellow curry pigment curcumin, as well as explore the molecular mechanisms of the potential anticancer effects of Theracurmin® on human prostate cancer and bladder cancer cells in vitro. The proliferation of cancer cells was examined by using the Cell Counting Kit-8. The clonogenic growth potential was determined by clonogenic assay. Cell cycle distribution was evaluated by flow cytometry using propidium iodide staining. Western blot analysis was applied to explore the expression patterns of molecules associated with apoptotic cell death and cell cycle checkpoint. We noted that Theracurmin® and curcumin exhibited similar anticancer effects in both androgen-dependent and -independent human prostate cancer cells in a dose- and time-dependent manner. These agents reduced cell viability and clonogenic growth potential by inducing apoptosis and cell cycle disturbance in human prostate cancer cells. Theracurmin® and curcumin also exerted marked anticancer effects on human bladder cancer cells, even in cisplatin-resistant T24R2 cells, in a dose- and time-dependent manner. Moreover, Theracurmin® and curcumin treatment decreased cell viability and clonogenicity via induction of apoptotic cell death and cell cycle dysregulation in human bladder cancer cells. In conclusion, our study suggests that Theracurmin® has potential as an anticancer agent in complementary and alternative medicine for these urological cancers.

Stratification of Contemporary Patients Undergoing Radical Prostatectomy for High-risk Prostate Cancer.

PURPOSE: Published data have shown heterogeneous outcomes for high-risk prostate cancer. Thus, we tried to identify more precise risk stratification system for contemporary high-risk prostate cancer. METHODS: Classifying patients according to National Comprehensive Cancer Network risk groups, we reviewed data of 1,905 men who underwent radical prostatectomy (RP) at our institution from 2006 to 2013. For our analyses, high-risk prostate cancers meeting at least one of two following factors were categorized as unfavorable high-risk prostate cancer: biopsy primary Gleason pattern 5 and/or multiple (≥2) high-risk criteria present. All other men with high-risk prostate cancer were designated as having favorable high-risk disease. Postoperative outcomes, including biochemical recurrence-free survivals were assessed and compared via log-rank test and Cox proportional hazards model. RESULTS: In multivariable analysis, primary Gleason 5 pattern on biopsy (p = 0.008) and multiple (≥2) high-risk criteria (p < 0.001) were observed to be independent predictors of the risk of biochemical recurrence amongst high-risk group undergoing RP. Favorable high-risk prostate cancer group showed a significantly higher 5-year biochemical recurrence-free survival than unfavorable high-risk group (56.35 vs. 18.75 %; log-rank test: p < 0.001). Favorable high-risk group demonstrated significantly lower 5-year biochemical recurrence-free survival than intermediate-risk group (56.07 vs. 82.05 %; log-rank test: p < 0.001). CONCLUSIONS: A significant heterogeneity existed in biochemical outcomes of contemporary patients with high-risk prostate cancer who underwent definitive RP. According to primary Gleason pattern and number of high-risk criteria present, high-risk group should be stratified further into favorable and unfavorable disease.

Visceral obesity in predicting oncologic outcomes of localized renal cell carcinoma.

PURPOSE: We investigate the clinicopathological features and prognostic significance of visceral obesity in patients with localized renal cell carcinoma. MATERIALS AND METHODS: This study included 706 patients with localized renal cell carcinoma who had undergone curative surgery between January 2003 and April 2012. Visceral, subcutaneous and total adipose tissue were measured based on preoperative computerized tomography of the umbilical region. Visceral adipose tissue percent was calculated using the formula, VAT% = [visceral adipose tissue/total adipose tissue] × 100. The association between clinicopathological factors and visceral obesity was examined. RESULTS: A higher VAT% at diagnosis was associated with older age at diagnosis, higher prevalence of diabetes and higher prevalence of former or current smoking status. The distribution of histological subtypes differed significantly among VAT% quartiles. The proportion of high grade tumors increased as VAT% increased (OR 1.023, 95% CI 1.000-1.126, p = 0.037). A U-shaped association between VAT% quartiles and the risk of disease recurrence was observed for all patients. Disease recurrence was significantly increased in the lowest (HR 3.198, 95% CI 1.765-10.040, p = 0.036) and highest (HR 4.760, 95% CI 2.937-13.210, p = 0.010) VAT% quartiles. CONCLUSIONS: Relative visceral obesity as assessed by VAT% was associated with clinicopathological characteristics of localized renal cell carcinoma. A U-shaped association between VAT% quartiles and risk of disease recurrence was observed among patients with localized renal cell carcinoma.