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Abstract: Approximately one-third of patients with prostate cancer show prostate-specific antigen (PSA) recurrence (biochemical failure) after a radical prostatectomy and are prone to developing metastasis with significant mortality. Although several clinicopathologic indicators, such as the PSA level, Gleason score, pathologic stage, and surgical-margin status, are used to predict outcomes after a curative-intended radical prostatectomy for localized prostate cancer, new biomarkers are still required to improve the prognosis and plan appropriate adjuvant therapy, particularly for patients at high risk of recurrence. DNA-based genetic biomarkers have several advantages over clinicopathologic indicators because they can be preoperatively examined, are easily evaluated, and can be interpreted more objectively without individual bias. In this study, the literature was reviewed from the PubMed database using the keywords “genetic polymorphisms” and “radical prostatectomy” from 1985 to April 2011. The results showed that genetic variants discovered from genome-wide association studies (such as rs1447295, rs1447295, rs6983561, rs13254738, Broad11934905, rs6983267, and rs7000448 at 8q24, rs7920517 and rs10993994 at 10q11, rs10486567 in the 7JAZF1, rs198977 in the KLK2, rs9282861 in the SULT1A1, and rs1536889 in the TLR4 gene) and single-nucleotide polymorphisms (SNPs) in important pathways (RUNX1, FGFR4, EGFR, VEGF, TNFRSF11B, vitamin D receptor, p53, WNT, inflammatory, androgen synthesis, and metabolism pathways) on prostate cancer occurrence and progression could serve as biomarkers to predict PSA recurrence after a radical prostatectomy. Including the genetic information might improve predictions of PSA recurrence after a radical prostatectomy. Future studies can be dedicated to confirming these findings in other ethnic cohorts and clarifying the roles of these SNPs/genes in the course of prostate cancer progression after a radical prostatectomy through functional analyses. [Copyright &y& Elsevier]

Purpose: Evidence is accumulating indicating that chronic inflammation plays an important role in prostate cancer. We investigated the potential prognostic roles of IL-6, IL-8 and IL-10 polymorphisms in clinical localized prostate cancer after radical prostatectomy. Materials and Methods: A total of 116 clinically localized prostate cancer patients undergoing curative radical prostatectomy were included in this study. The IL-6, IL-8 and IL-10 polymorphisms were determined by the TaqMan real-time PCR method. Their prognostic significance on prostate-specific antigen (PSA) recurrence was assessed using Kaplan-Meier analysis and Cox regression model. Results: The IL-6 polymorphism (rs2066992) T/G and G/G genotype cases were associated with a higher percentage of preoperative PSA levels of ≥10 ng/ml; higher risk of positive surgical margin, and higher risk of extraprostatic extension compared to the T/T genotype. The IL-10 polymorphism (rs1800871) A/A genotype was associated with a higher risk of PSA recurrence compared with the A/G + G/G genotypes and significantly poorer PSA-free survival (log-rank test, p = 0.019). After considering other covariates in a Cox proportional hazard model, the IL-10A/A genotype and high Gleason score (8–10) were still independent predictors of poor PSA-free survival. Conclusion: Our results suggest that the IL-10 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: The CDKN1B (p27) V109G polymorphism has been suggested to confer the risk of advanced prostate cancer in Caucasian males. However, its prevalence in Asian populations has never been reported. The aim of this study was to determine the CDKN1B V109G polymorphism frequency in the low incidence Taiwanese population and investigate its potential role on prostate cancer susceptibility and disease progression. Methods: A hospital-based case-control study was conducted, which enrolled a total of 190 prostate cancer patients and 292 age-matched male controls. PCR-RFLP was used to determine the CDKN1B V109G polymorphism. The association between CDKN1B V109G and prostate cancer risk and clinicopathologic variables was analyzed. Results: The variant CDKN1B G allele frequency in Taiwanese males appears to be low (2.1%). Overall, there was no significant association between CDKN1B V109G polymorphism and prostate cancer risk. Similarly, no significant findings were found when further stratified by different age groups, disease stages, and pathological grades. In terms of disease outcome, the CDKN1B V109G genotypes were not associated with either hormone response status after hormone therapy (p = 0.730) or with prostate-specific antigen recurrence for clinically localized prostate cancer patients who receive radical prostatectomy (p = 0.536). Conclusions: There was a low prevalence of CDKN1B V109G polymorphism in Taiwanese compared to Caucasian males. Hence, it may not be an appropriate biomarker of prostate cancer among the Taiwanese population. Further large-scale studies are needed to clarify the role of CDKN1B V109G polymorphism on prostate cancer risk. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Increasing studies reported genetic susceptibility to drug hypersensitivity reactions, as exemplified by the HLA-A*31:01 and HLA-B*15:02 association with carbamazepine (CBZ)-induced hypersensitivity reactions, such as maculopapular exanthema (MPE), drug rash with eosinophilia and systemic symptoms (DRESS), and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective: To carry out a comprehensive analysis on the clinical spectrum and HLA genotype–phenotype correlations in CBZ-induced hypersensitivity reactions. Methods: We analyzed the clinical information of 194 patients with CBZ hypersensitivity (51 MPE, 23 DRESS, 112 SJS/TEN, and 8 cases with other phenotypes), and 152 CBZ-tolerant controls. All are Han Chinese. We examined the HLA-A/HLA-B genotypes, gene dosage, and drug dosage effects. Results: CBZ-SJS/TEN showed the strongest association with the HLA-B*15:02 allele (Pc=5.8×10−43; odds ratio (OR) (95% CI)=97.6(42.0–226.8)), in which HLA-B*15:02 was identified in all patients (25/25) with SJS/TEN with >5% body surface area (BSA) skin detachment, but lost its 100% association (85.1%, 74/87) in SJS with <5% BSA detachment. In contrast, HLA-B*40:01 showed negative association with CBZ-induced SJS/TEN ((Pc=8.3×10−5; OR (95% CI)=0.22(0.1–0.4)). By comparison, CBZ-induced MPE/DRESS had no association with HLA-B*15:02, but linked to HLA-A*31:01 (Pc=2.7×10−3; OR (95% CI)=6.86(2.4–19.9), and HLA-B*51:01 (Pc=0.01; OR (95% CI)=4.56(2.0–10.5)). No gene dosage or CBZ dosage effects was observed. Conclusion: This study reported the different strength of HLA association with CBZ hypersensitivity in Han Chinese. With the increasing application of pharmacogenetic markers, the HLA genotype–phenotype correlations and the results of the test need to be carefully interpreted for CBZ-induced hypersensitivity reactions. [Copyright &y& Elsevier]

Objectives: The CYP19 gene encodes aromatase—a key enzyme involved in the conversion of androstenedione/testosterone to estrone/estradiol. In this study, we analyzed the association between the TCT insertion (Ins)/deletion (Del) and TTTA repeat polymorphisms of CYP19 and prostate cancer (PCa). Methods: Automated sequencer with GeneScan software was used to determine the CYP19 gene polymorphisms in peripheral blood mononuclear cell DNA from 244 patients with PCa and 261 age-matched healthy male controls. The distribution of Stage I to IV was 3.4%, 23.8%, 19.6%, and 53.2%, respectively. The Gleason score was 2 to 5 in 22.9%, 6 to 7 in 53.2%, and 8 to 10 in 23.8%. Results: The frequency of the TCT Del/Del genotype in the Taiwanese patients with PCa (12.3%) was significantly greater than that in the controls (5.4%; P = 0.015, odds ratio [OR] 2.43, 95% confidence interval [CI] 1.23 to 4.80). Individuals with a homozygous A1 (seven TTTA repeats) genotype had a significantly greater risk of developing PCa (OR 1.59, 95% CI 1.04 to 2.44, P = 0.044). The frequency of the Ins-A6 (12 TTTA repeats) haplotype was significantly greater in the control group than in the patient group (9.8% versus 6.1%, OR 0.61, 95% CI 0.38 to 0.97). The OR of developing PCa for men with the homozygous Del-A1 diplotype was 2.31 (95% CI 1.10 to 4.83). Conclusions: The results of our study have shown that the CYP19 TCT Del/Del genotype might be a susceptibility marker for PCa. Men with the Ins-A6 haplotype had a lower risk of developing PCa. [Copyright &y& Elsevier]

Recent molecular epidemiological studies have shown that the inherited polymorphisms of VDR gene may be linked to prostate cancer risk and its aggressive phenotypes. However, the findings remain inconclusive. In this study, we investigated the association of the BsmI, ApaI and TaqI polymorphisms of VDR gene with prostate cancer risk in a Taiwanese population. In total, 160 prostate cancer patients and 205 age-matched male controls were studied between December 2000 and February 2003. No significant associations were found between the ApaI and TaqI polymorphisms and the risk of prostate cancer. However, the control group was found to have a significantly higher frequency of the BsmI ‘BB’ and ‘Bb’ genotypes (15.6%) than prostate cancer patients (8.1%). After adjustment for age, patients with BsmI ‘BB’ or ‘Bb’ genotypes were associated with a twofold decreased risk (OR=0.50; 95%CI=0.25–0.98; P=0.045) for developing prostate cancer than those with ‘bb’ genotypes. This effect was particularly significant among men below the median age of 72 years (P=0.017). Moreover, stronger associations were found in the advanced stages (T3/T4/N1/M1) and poorly differentiated disease (Gleason score≥7) (‘BB’ and ‘Bb’ vs ‘bb’: OR=0.25; 95%CI=0.07–0.83; P=0.024 and OR=0.25; 95%CI=0.07–0.85; P=0.026, respectively). Our findings suggest that the VDR BsmI polymorphism may play a significant role in the development of prostate cancer. [Copyright &y& Elsevier]

Four novel small nucleolar RNAs (snoRNAs), h5sn1, h5sn2, h5sn3, and h5sn4, were successfully amplified from human total RNAs using RT-PCR. They exhibited the structural hallmarks of box H/ACA snoRNAs and formed sequence complementarity to 5S rRNA. The nucleotide sequences of the snoRNAs from different donors were highly conserved as evidenced by single-stranded conformational polymorphism and direct nucleotide sequence analysis. Although their host genes had no protein-coding potential, the expression of the snoRNAs was differentially displayed in different tissues. Noticeably, h5sn2 was highly expressed in normal brain, but its expression drastically decreased in meningioma. This opens the fascinating possibility of the relationship between the processing of snoRNAs and carcinogenesis. [Copyright &y& Elsevier]