Chia-Cheng Yu

Risk Factors for Individual Domains of Female Sexual Function

INTRODUCTION Female sexual function contains four major subtypes of desire, arousal, orgasm, and pain. Few studies used validated instruments to determine the dysfunction in these areas and assess their risk factors. AIM To assess the prevalence of and risk factors for individual components of sexual difficulty in women. METHODS A self-administered questionnaire containing the Female Sexual Function Index (FSFI) was given to 2,159 woman employees of two hospitals to assess their sexual function and its correlates. MAIN OUTCOME MEASURES The associations between female sexual difficulty in individual domains defined by the FSFI domain scores and potential risk factors assessed by simple questions. RESULTS Among the 1,580 respondents, 930 womens data were eligible for analysis with a mean age of 36.1 years (range 20-67). Of them, 43.8% had sexual difficulty in one or more domains, including low desire in 31.3%; low arousal, 18.2%; low lubrication, 4.8%; low orgasmic function, 10.4%; low satisfaction, 7.3%; and sexual pain, 10.5%. Compared with the younger women (20-49 years), the oldest age group (50-67 years) had a significantly higher prevalence in low desire, low arousal, and low lubrication, but not in the other domains. Based on multivariate logistic regression analyses, poor relationship with the partner and perception of partners sexual dysfunction were major risk factors for low desire, low arousal, low orgasmic function, and low satisfaction. Age and urge urinary incontinence were associated with low lubrication and sexual pain. Most comorbidities were not related to these difficulties, except diabetes being related to low desire. CONCLUSIONS Relationship factors had substantial impact on female sexual function in desire, arousal, orgasm, and satisfaction. On the other hand, womens lubrication problem and sexual pain were related predominantly with biological factors. These are initial results and future research is needed to confirm them.

Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age‐matched male controls and 189 non age‐matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00–4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8–10) (OR, 2.47; 95% CI, 1.20–5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate‐specific antigen (PSA) recurrence‐free survival (hazard ratio = 3.25, 95% CI = 1.32–8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early‐onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy.

Impact of prostate-specific antigen (PSA) nadir and time to PSA nadir on disease progression in prostate cancer treated with androgen-deprivation therapy

The influence of PSA kinetics on the outcome of metastatic prostate cancer after androgen deprivation therapy (ADT) is not well understood. We evaluated the prognostic significance of PSA nadir and time to PSA nadir as well as their potential interactive effect on the progression of disease after ADT.

Prognostic Significance of p53 and X-ray Repair Cross-complementing Group 1 Polymorphisms on Prostate-Specific Antigen Recurrence in Prostate Cancer Post–Radical Prostatectomy

Purpose: The tumor suppressor p53 and DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) are thought to play important roles on prostate cancer susceptibility and tumor development. We investigated the potential prognostic roles of p53 (codon 72) and XRCC1 (codons 194, 280, and 399) polymorphisms in clinical localized prostate cancer after radical prostatectomy. Experimental Design: A total of 126 clinical localized prostate cancer patients undergoing curative radical prostatectomy at the Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital were included in this study. The p53 codon 72 and XRCC1 codons 194, 280 and 399 polymorphisms were determined by the PCR-RFLP method. Their prognostic significance on prostate-specific antigen (PSA) recurrence were assessed using the Kaplan-Meier analysis and Cox regression model. Results: The p53 codon 72 Arg/Arg genotype was associated with increased PSA recurrence risk compared with the Arg/Pro and Pro/Pro genotypes, although the difference did not reach significance (30.3% versus 20.4%, P = 0.247). Of these three XRCC1 polymorphisms, the codon 399 Arg/Gln + Gln/Gn genotypes were significantly associated with higher risk of PSA recurrence after radical prostatectomy compared with the Arg/Arg genotype (34.0% versus 15.1%, P = 0.013) and poorer PSA-free survival (log-rank test, P = 0.0056). After considering for other covariates in a Cox proportional hazard model, the XRCC1 Arg/Gln and Gln/Gln genotypes (hazard ratio, 4.73; 95% confidence interval, 1.61-13.92; P = 0.005) and high Gleason score (Gleason score, 8-10; hazard ratio, 5.58; 95% confidence interval, 1.58-19.71; P = 0.008) were still independent predictors of poor PSA-free survival after radical prostatectomy. The similar significant results were not found in XRCC1 codons 194 and 280. Conclusions: Our results suggest that the XRCC1 codon 399 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.

Effect of the organotin compound triethyltin on Ca2+ handling in human prostate cancer cells.

The effects of triethyltin on Ca2+ mobilization in human PC3 prostate cancer cells have been explored. Triethyltin increased [Ca2+]i at concentrations larger than 3 microM with an EC50 of 30 microM. Within 5 min, the [Ca2+]i signal was composed of a gradual rise and a sustained phase. The [Ca2+]i signal was reduced by half by removing extracellular Ca2+. The triethyltin-induced [Ca2+]i increases were inhibited by 40% by 10 microM nifedipine, nimodipine and nicardipine, but were not affected by 10 microM of verapamil or diltiazem. In Ca2+-free medium, pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca+ pump inhibitor, reduced 200 microM triethyltin-induced Ca+ increases by 50%. Pretreatment with U73122 (2 microM) to inhibit phospholipase C did not alter 200 microM triethyltin-induced [Ca2+]i increases. Incubation with triethyltin at a concentration that did not increase [Ca2+]i (1 microM) in Ca2+-containing medium for 3 min potentiated ATP (10 microM)- or bradykinin (1 microLM)-induced [Ca2+]i increases by 41 +/- 3% and 51 +/- 2%, respectively. Collectively, this study shows that the environmental toxicant triethyltin altered Ca2+ handling in PC3 prostate cancer cells in a concentration-dependent manner: at higher concentrations it increased basal [Ca2+]i; and at lower concentrations it potentiated agonists-induced [Ca2+]i increases.

Androgen receptor gene polymorphism and prostate cancer in Taiwan

BACKGROUND AND PURPOSE The length of polymorphic CAG trinucleotide repeats in the polyglutamine region of the androgen receptor (AR) gene has been suggested to be inversely correlated with the transactivation function of the AR. An increase in androgen activity may be associated with prostate cancer, and ethnic variations in CAG repeat length may contribute to varying prostate cancer risks in different populations. This case-control study investigated the potential role of AR polymorphism in prostate cancer risk in Taiwanese. METHODS Sixty six pathologically-confirmed prostate cancer patients and 104 controls were studied. CAG repeat polymorphism was genotyped by a polymerase chain reaction (PCR)-based direct sequencing method. Logistic regression was used to determine the relative risk of AR gene CAG number on prostate cancer risk. The associations of AR-CAG polymorphism with disease stage, pathologic grade, and age at diagnosis were assessed. AR-CAG repeat number was first treated as a continuous variable, then was divided into short and long groups (n < 23 vs n > or = 23) for categorical analysis. The extreme groups of AR-CAG distribution were also analyzed for these associations (n < or = 20 vs n > or = 26 and n = 21-25 vs n > or = 26). RESULTS The mean number of CAG repeats in patients and controls was similar: 23.2 +/- 3.0 (range, 15 to 31) and 22.9 +/- 3.1 (range, 15 to 31), respectively. No association was found between AR-CAG repeat polymorphism and disease stage (p = 0.30), histological grade (p = 0.49), or age at diagnosis (p = 0.51). After adjusting for other covariates (age, body mass index, education level, smoking, and alcohol status), the number of AR-CAG repeats was not significantly associated with prostate cancer risk [odds ratio (OR) = 0.97, 95% confidence interval (95% CI) = 0.72 to 1.31; p = 0.84]. In categorical analysis, men with short CAG repeats (n < 23) did not have increased risk for prostate cancer (OR = 0.45, 95% CI = 0.29 to 1.05) compared to those with long CAG repeats (n > or = 23). Non-significant differences in prostate cancer risk were also found when comparing the extreme short group (n < or = 20) and the intermediate group (n = 21-25) to the extreme long group (n > or = 26) [n < or = 20 vs n > or = 26: OR = 1.00, 95% CI = 0.34 to 3.00; n = 21-25 vs n > or = 26: OR = 0.82, 95% CI = 0.37 to 1.81]. CONCLUSIONS The results of this study do not support an important effect of AR-CAG repeat polymorphism on prostate cancer risk. A large-scale study is needed to clarify genetic components of prostate cancer risk in the Taiwanese population.

Genetic variants in microRNAs and microRNA target sites predict biochemical recurrence after radical prostatectomy in localized prostate cancer

Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ‐confined prostate cancer who had a median follow‐up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single‐nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan–Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16–2.21, p for trend = 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15–2.08, p for trend = 0.004) and in combined analysis (HR 1.57, 95% CI 1.26–1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and microRNA target sites can be predictive biomarkers for BCR after RP.

Molecular Markers in Key Steroidogenic Pathways, Circulating Steroid Levels, and Prostate Cancer Progression

Purpose: Prostate cancer is a heterogeneous genetic disease, and molecular methods for predicting prognosis in patients with aggressive form of the disease are urgently needed to better personalize treatment approaches. The objective was to identify host genetic variations in candidate steroidogenic genes affecting hormone levels and prostate cancer progression. Experimental Design: The study examined two independent cohorts composed of 526 Caucasian men with organ-confined prostate cancer and 601 Taiwanese men on androgen–deprivation therapy. Caucasians were genotyped for 109 haplotype-tagging single-nucleotide polymorphisms (SNP) in CYP17A1, ESR1, CYP19A1, and HSD3B1, and their prognostic significance on disease progression was assessed using Kaplan–Meier survival curves and Cox regression models. Positive findings, including previously identified SRD5A1, SRD5A2, HSD17B2, HSD17B3, and HSD17B12 polymorphisms, were then explored in Taiwanese men (n = 32 SNPs). The influence of positive markers on the circulating hormonal levels was then appraised in Caucasians using specific and sensitive mass spectrometry–based methods. Results: After adjusting for known risk factors, variants of CYP17A1 (rs6162), HSD17B2 (rs4243229 and rs7201637), and ESR1 (rs1062577) were associated with progressive disease in both cohorts. Indeed, the presence of these variations was significantly associated with progression in Caucasians (HR, 2.29–4.10; P = 0.0014–2 × 10−7) and survival in Taiwanese patients [HR = 3.74; 95% confidence interval (CI): 1.71–8.19, P = 0.009]. Remarkably, the CYP17A1 rs6162 polymorphism was linked to plasma dehydroepiandrosterone-sulfate (DHEA-S) levels (P = 0.03), HSD17B2 rs7201637 with levels of dihydrotestosterone (P = 0.03), and ESR1 rs1062577 with levels of estrone-S and androsterone-glucuronide (P ≤ 0.05). Conclusion: This study identifies, in different ethnic groups and at different disease stages, CYP17A1, HSD17B2, and ESR1 as attractive prognostic molecular markers of prostate cancer progression. Clin Cancer Res; 19(3); 699–709. ©2012 AACR.

Intradiverticular tumors of the bladder: surgical implications--an eleven-year review.

An 11-year review of all vesical diverticula and bladder tumors was undertaken. Fourteen patients were found to have primary neoplasms arising in the diverticula. The most common type was transitional cell. Hematuria was the most common presentation. Diagnosis is relatively difficult and treatment is not well defined. Lack or thinness of muscular layer of the diverticulum also potentiates early peridiverticular invasion and results in poor prognosis. Early diagnosis and adequate treatment are indicated.

Significant associations of prostate-specific antigen nadir and time to prostate-specific antigen nadir with survival in prostate cancer patients treated with androgen-deprivation therapy

Objective. The influence of prostate-specific antigen (PSA) kinetics on the outcome of metastatic prostate cancer (PCa) after androgen-deprivation therapy (ADT) remains poorly characterised. We evaluated the prognostic significance of PSA nadir and time to PSA nadir as well as their interactive effect on prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT. Methods. A total of 650 men with advanced or metastatic PCa treated with ADT were studied. The prognostic significance of PSA nadir and time to PSA nadir on PCSM and ACM were analysed using Kaplan–Meier analysis and the Cox regression model. Results. On multivariate analysis, clinical M1 stage, Gleason Score 8–10, PSA nadir ≥ 0.2 ng/ml and time to PSA nadir < 10 months were independent predictors of PCSM and ACM. The combined analysis showed that patient with higher PSA nadir and shorter time to PSA nadir had significantly higher risk of PCSM and ACM compared to those with lower PSA nadir and longer time to PSA nadir (hazard ratios = 6.30 and 4.79, respectively, all P < 0.001). Conclusions. Our results suggest that higher PSA nadir level and faster time to reach PSA nadir after ADT were associated with shorter survival for PCa.