Association of variants in estrogen-related pathway genes with prostate cancer risk.
ABSTRACT BACKGROUND: Through mediation of estrogen receptors, estradiol has been shown to have both carcinogenic and anti-carcinogenic effects on the prostate. We performed a population-based case-control study to investigate variants in estrogen-related genes ESR1, ESR2, CYP19A1, CYP1A1, and CYP1B1 and the potential association with risk of prostate cancer (PCa). MATERIALS AND METHODS: We evaluated PCa risk conferred by 73 single nucleotide polymorphisms in 1,304 incident PCa cases and 1,266 age-matched controls. Analysis included stratification by clinical features and assessment of environmental modifiers. RESULTS: There was evidence of altered risk of developing PCa for variants in ESR1, CYP1A1, and CYP1B1, however, only CYP1B1 rs1056836 retained significance after adjustment for multiple comparisons. An association with risk for more aggressive PCa was observed for variants in ESR1, ESR2, and CYP19A1, but none was significant after adjustment for multiple comparisons. There was no effect modification by obesity. CONCLUSIONS: Germline genetic variation of these estrogen pathway genes may contribute to risk of PCa. Additional studies to validate these results and examine the functional consequence of validated variants are warranted. Prostate © 2012 Wiley Periodicals, Inc.
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ABSTRACT: The Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates. Previous studies have reported the existence of CYP1B1 L432V missense polymorphism in prostate, bladder and renal cancers. However, the effects of this polymorphism on the risk of these cancers remain conflicting. Therefore, we performed a meta-analysis to assess the association between L432V polymorphism and the susceptibility of urinary cancers.Diagnostic pathology. 06/2014; 9(1):113.
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ABSTRACT: Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti‑oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications.International journal of oncology. 07/2014;
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ABSTRACT: The purpose of this study was to determine the impact of obesity on clinicopathological features and biochemical recurrence (BCR) following radical prostatectomy (RP) in Korean prostate cancer (PCa) patients. A single-institutional retrospective analysis was performed on 880 PCa patients treated by RP without neoadjuvant therapy between July 2005 and December 2011. Patients were stratified according to body mass index (BMI) standards for Asian populations: obese (BMI ≥25 kg/m(2)), overweight (BMI 23-24.9 kg/m(2)), or normal weight (BMI <23 kg/m(2)). For analysis, overweight and obese patients were combined (n = 592, BMI ≥23 kg/m(2)) and compared with normal weight patients (n = 288, BMI <23 kg/m(2)). BCR was defined as prostate-specific antigen (PSA) ≥0.2 ng/ml following RP. Normal weight patients tended to be classified into the higher D'Amico risk category with smaller prostate volumes compared with obese and overweight patients. Normal weight patients had higher pathological Gleason scores and were at higher risk of BCR during the mean follow-up of 58.2 months. This translated to a higher 5-year BCR-free survival rate for obese and overweight patients compared with normal weight patients (77.8 vs. 70.3 %; p = 0.017). On multiple Cox-proportional hazards regression analysis incorporating variables of BMI category, PSA, positive surgical margins, pathological T stage, and Gleason score, higher BMI category remained a significant predictor of a lower risk of BCR (HR = 0.634, p = 0.028). Obese and overweight Korean PCa patients have lower Gleason scores and a reduced risk of BCR compared with normal weight patients. These findings suggest that body fat influences pathological features and oncologic outcomes of PCa.International Urology and Nephrology 05/2014; · 1.33 Impact Factor