Chia-Chu Liu

Prognostic Significance of Prostate Cancer Susceptibility Variants on Prostate-Specific Antigen Recurrence after Radical Prostatectomy

Recent genomewide association studies have identified several prostate cancer susceptibility variants. However, the association between these variants and biochemical failure in prostate cancer patients receiving radical prostatectomy has not been determined. We systematically evaluated 20 prostate cancer–associated single-nucleotide polymorphisms in a cohort of 320 localized prostate cancer patients receiving radical prostatectomy. Each single-nucleotide polymorphism found to be associated with the recurrence of prostate-specific antigen was further analyzed by Kaplan-Meier analysis and Cox regression model. Three prostate cancer susceptibility single-nucleotide polymorphisms (rs1447295 at 8q24, rs7920517 and rs10993994 at 10q11) were associated with prostate-specific antigen recurrence (P < 0.02). Of these, rs7920517 and rs10993994, which were in strong linkage disequilibrium (r2 = 0.91), also showed significant associations with poor prostate-specific antigen–free survival following radical prostatectomy (log-rank test; P < 0.01). The associations remained significant in our multivariate Cox proportional hazards analysis after adjusting for other clinicopathologic risk covariates (P < 0.01). In conclusion, loci associated with risk for prostate cancer, such as rs7920517 and rs10993994, might also be used to predict the recurrence of prostate-specific antigen in prostate cancer patients receiving radical prostatectomy. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3068–74)

The Prevalence of and Risk Factors for Androgen Deficiency in Aging Taiwanese Men

INTRODUCTION Androgen deficiency in aging men has attracted much medical interest. Most studies on androgen deficiency have been conducted in Caucasian populations, and data from other ethnicities are lacking. AIM To evaluate the prevalence of and risk factors for androgen deficiency and symptomatic androgen deficiency in Taiwanese men over 40 years old. METHODS From August 2007 to April 2008, a free health screening was conducted by a medical center in Kaohsiung, Taiwan, and 819 men participated in this health screening. All participants completed a health questionnaire, received a detailed physical examination, and blood samples were drawn between 8:00 and 12:00 am. MAIN OUTCOME MEASURES Serum total testosterone (TT), albumin, and sex hormone-binding globulin levels were measured. The level of free testosterone (FT) was calculated. Clinical symptoms of androgen deficiency were assessed using the Androgen Deficiency in the Aging Male (ADAM) questionnaire. RESULTS Seven hundred thirty-four men who met the inclusion criteria (mean age 57.4 +/- 6.7 years; range: 43-87 years) were included in this study. The prevalence of androgen deficiency was 24.1% based on the criterion of TT level < 300 ng/dL, and 16.6% based on the criterion of both TT < 300 ng/dL and FT < 5 ng/dL. The prevalence of symptomatic androgen deficiency was 12.0%. Both prevalence of androgen deficiency and symptomatic androgen deficiency increased with age. Older age, obesity, and diabetes mellitus were independent risk factors for androgen deficiency and symptomatic androgen deficiency. CONCLUSIONS In a sample of aging Taiwanese men, a substantial proportion had androgen deficiency and symptomatic androgen deficiency, and the prevalence increased with age. Older age, obesity, and diabetes mellitus were independent risk factors for androgen deficiency and symptomatic androgen deficiency. Those potentially modifiable risk factors like obesity and diabetes mellitus should be prevented to maintain normal testosterone levels during aging in men.

The Potential Impact of Metabolic Syndrome on Erectile Dysfunction in Aging Taiwanese Males

INTRODUCTION Recently, metabolic syndrome (MtS) has received increasing attention. However, investigations regarding the potential impact of MtS and its components on erectile dysfunction (ED) have not been completely clarified. AIM To determine the potential impact of MtS on ED in aging Taiwanese males. MAIN OUTCOME MEASURE The definition of MtS was according to the modified criteria developed by the Bureau of Health Promotion in Taiwan. The presence and severity of ED were evaluated by International Index of Erectile Function 5 (IIEF-5) scores. METHODS A total of 639 subjects with a mean age of 60.2 years (range 40-83) were enrolled during a free health screening. All the men had complete clinical data and questionnaires taken. Clinical variables were compared according to MtS and ED prevalence. Multiple logistic regression analysis was used to determine the independent predictors of ED and MtS. RESULTS Using age-adjusted multivariate logistic regression analysis, our results showed that subjects with ED had significantly higher prevalence of MtS (P<0.01, OR=2.30, 95% CI: 1.44-3.69). The presence of MtS had significant correlation with lower IIEF-5 scores (P<0.01), which were associated with the increment of MtS components number (P<0.01). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor of MtS for ED (P=0.01, OR=1.60, 95% CI: 1.09-2.35). Testosterone levels were significantly lower in subjects with MtS (P=0.05), while inversely correlated with number of MtS components (P<0.01). CONCLUSIONS In aging Taiwanese males, the presence of MtS is strongly associated with ED and abnormal FBG is the most independent predictor for ED. Low testosterone level might be viewed as another possible common denominator for various pathologies linking MtS to ED.

Urinary Stone Analysis of 1,000 Patients in Southern Taiwan

Urolithiasis is a common urologic disease. Stones may occur in the kidney, ureter, or urinary bladder. We collected 1,000 stone samples in the subtropical area of southern Taiwan. Stone components were analyzed by Fourier transform infrared spectroscopy. Mixed components of calcium oxalate and calcium phosphate were the most common form of stones (52.3%), followed by calcium oxalate (27.8%) and calcium phosphate (9.3%). Uric acid stones accounted for 7.6%. Magnesium ammonium phosphate stones accounted for 3.0%. Only one cystine stone was found. In the study of urinary stone formation mechanism and prevention of recurrent urolithiasis, knowing the stone composition is important.

High melamine migration in daily-use melamine-made tableware

Melamine is commonly used to manufacture tableware, and this could be one of the important exposure sources in humans. The study aims to measure melamine migrated from different material-made tableware by the most sensitive technique of liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test samples were filled with pre-warmed designated-temperature (from room temperature (∼20 °C), 30 °C, 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, to 90 °C) simulant (either distilled water or 3% acetic acid) up to 20 ml and immersed in a water bath at that designated temperature for 15 or 30 minutes (min). High melamine migration levels, ranging from 6.97 to 19.03 μg/ml, can be measured from all melamine-made samples containing 20 ml 3% acetic acid in water bath of 90 °C for 30 min, whereas melamine cannot be detectable in all other material-made samples in the same condition. In addition, the cheaper the melamine-made tableware samples, the higher the melamine migration levels. The migration of melamine amount is dependent on different temperatures, contact times, simulant, and prices of tableware. Since tableware is used in daily life, it is prudent to cautiously select materials that contain foodstuffs.

The Associations Among eNOS G894T Gene Polymorphism, Erectile Dysfunction, and Benign Prostate Hyperplasia‐Related Lower Urinary Tract Symptoms

INTRODUCTION A number of literature has now identified the role of impaired nitric oxide synthase/nitric oxide pathway in the endothelium as the central to the development of erectile dysfunction (ED) and benign prostate hyperplasia-related lower urinary tract symptoms (BPH/LUTS). Recently a few studies have reported the associations between endothelial nitric oxide synthase (eNOS) G894T gene polymorphisms and ED. However, there has been no report investigating the eNOS G894T genetic susceptibility factor for both ED and BPH/LUTS. AIM To investigate the possible associations among eNOS G894T polymorphism, ED, and BPH/LUTS in a Taiwanese population. MAIN OUTCOME MEASURES Patients with ED were defined as those having a 5-item International Index of Erectile Function-5 <21. METHODS In all, 372 Taiwanese men underwent a free health screening were enrolled. All the men had complete clinical data and questionnaires taken. The eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS Three hundred seventy-two men had a mean (standard deviation) age of 60.2 (8.8) years. With multivariate analysis, our data identified that aging, diabetes mellitus (DM), and eNOS G894T gene polymorphism were three independent common risk factors for both ED and BPH/LUTS (P < 0.001, P = 0.036, and P = 0.039 for ED; P = 0.034, P = 0.004, and P = 0.016 for BPH/LUTS, respectively). The eNOS 894T allele carriers had significantly higher prevalence of ED (77.9% vs. 60.4%, P = 0.012) and higher International Prostate Symptom score (IPSS) (13.3 +/- 10.7 vs. 9.3 +/- 7.8, P = 0.001) than G allele carriers. CONCLUSIONS Our results showed that aging, DM, and eNOS 894T allele carrier gene polymorphism were the three independently common risk factors for both ED and BPH/LUTS in the Taiwanese population. The eNOS 894T allele carriers had significantly higher frequencies of ED and higher IPSS, suggesting that eNOS G894T gene polymorphisms may play an implication as a genetic susceptibility factor for both ED and BPH/LUTS.

The impact of cigarette smoking, alcohol drinking and betel quid chewing on the risk of calcium urolithiasis.

PURPOSE To evaluate the independent and combined effects of alcohol drinking, cigarette smoking and betel quid chewing on the risk of calcium urolithiasis. METHODS A total of 354 cases diagnosed with calcium urolithiasis and 354 age- and sex-matched healthy controls were recruited from Kaohsiung Medical University Hospital between June 2003 and February 2007. All subjects completed a detailed questionnaire survey and provided blood and urine samples for biochemical evaluation. RESULTS Current cigarette smoking (odds ratio [OR], 1.66; 95% confidence interval [95%CI], 1.11-2.50; p=0.014) and current betel quid chewing (OR, 1.97; 95%CI, 1.06-3.64; p=0.032), but not current alcohol drinking, were found to be independent risk factors for the development of calcium urolithiasis. The joint risk of current cigarette smoking and current betel quid chewing was increased 3.73-fold (OR, 3.73; 95%CI, 1.81-7.70, p<0.001) compared to those who had neither habit. CONCLUSIONS Both cigarette smoking and betel quid chewing are independent risk factors for the development of calcium urolithiasis. The risk effect is even strengthened when subjects have both habits. These findings suggest users can greatly reduce the risk of calcium urolithiasis if they quit these two habits.

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.

Low exposure to melamine increases the risk of urolithiasis in adults

Melamine, a widely used chemical found in many products in daily use, became a public health concern due to melamine-associated urinary stone formation in children. In adults, it is still unknown whether low-dose melamine exposure may also cause urolithiasis. To address this question, we studied 211 Taiwanese patients diagnosed with calcium urolithiasis and 211 age- and gender-matched controls. All patients completed a detailed questionnaire and provided blood and urine samples for biochemical analysis. Urinary melamine concentrations were measured by triple-quadrupole liquid chromatography tandem mass spectrometry. Compared with those whose urinary melamine levels were below the detection limit of the method, patients with urinary melamine levels of up to 3.11  ng/ml and those with levels of ≥3.12  ng/ml had 3.01- and 7.64-fold increased risk, respectively, of calcium urolithiasis after adjusting for educational level, fluid intake, cigarette smoking, betel quid chewing, alcohol drinking, urinary uric acid, calcium, creatinine, and estimated creatinine clearance rate. The population attributable risk of calcium urolithiasis averaged 50% when melamine was detected in the urine, after considering other covariates. MALDI-TOF mass spectrometry detected melamine in the stones of nine representative patients who had measurable urinary melamine levels. Thus, low-dose melamine exposure can play an important role in calcium urolithiasis in Taiwanese adults.

Urinary melamine and adult urolithiasis in Taiwan

BACKGROUND This study aims to investigate the association between urinary melamine concentration and the risk of urolithiasis in adult. METHODS From 2003 to 2007, 11 and 22 patients diagnosed with upper urinary tract uric acid urolithiasis and calcium urolithiasis, respectively, were recruited from Kaohsiung Medical University Hospital. For comparison, we randomly collected 22 sex- and age-matched subjects who come to the same hospital for regular health check-up at the same period of time. Urinary melamine concentration was measured by the method of triple-quadrupole liquid chromatography tandem mass spectrometry (LC-MS/MS). Wilcoxon rank sum test was used to compare the urinary melamine concentrations in uric acid urolithiasis patients with controls as well as in calcium urolithiasis patients with controls. FDR (false discovery rate) was used to correct the p-values for two comparisons. RESULTS Subjects with uric acid urolithiasis (median: 0.50 vs 0.06microg/mmol creatinine, Wilcoxon test: FDR_p=0.024) and with calcium urolithiasis (median: 0.14 vs 0.06, FDR_p=0.024) had significantly higher urinary melamine concentration than controls. Based on the ROC curves, subjects whose melamine levels were over 0.262 and 0.037microg/mmol creatinine, respectively, might have significant risks to have uric acid and calcium urolithiasis. CONCLUSION This preliminary study suggests that exposure to even low-dose melamine-related products still have the potential to develop both uric acid and calcium urolithiasis in adults.