Vitamin D receptor gene polymorphism and prostate cancer risk

BACKGROUND: 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts antiproliferative effect on prostatic cells, mediated through the vitamin D receptor. In a case-control study, we examined whether the vitamin D receptor (VDR) gene polymorphism in exon 9 could affect prostate cancer susceptibility. METHODS: One hundred ninety newly diagnosed prostate cancer patients and 190 age-matched men with benign prostatic hyperplasia (BPH), in whom the presence of prostate cancer was excluded clinically or histologically, were recruited for this study. The VDR TaqI polymorphism was investigated by polymerase chain reaction (PCR) following restriction fragment length polymorphism using DNA from lymphocytes. Depending on the presence or absence of the TaqI restriction site at the third position of codon 352, patients were classified as TT, Tt, or tt. RESULTS: The frequency of the tt genotype was not significantly different between prostate cancer patients (18%) and controls (12%; P = 0.07). The odds ratio (OR), calculated relative to individuals with the TT genotype was 1.76 (95% confidence limit (CL) = 0.90-3.45). After stratification for Gleason score and prostate specific antigen levels in a case-case comparison (n = 190), no significant associations with the VDR genotypes were detectable either. CONCLUSIONS: In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.     

Polymorphisms in the vitamin D receptor gene and the androgen receptor gene and the risk of benign prostatic hyperplasia

OBJECTIVE: Little is known about risk factors for the development of benign prostatic hyperplasia (BPH). Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene. Since both receptors are relevant for prostate growth, the VDR and AR are also expected to be involved in the development of BPH. The objective of this study is to establish the relationship between the risk of BPH and a polymorphism in the number of CAG repeats in the AR gene and a TaqI restriction enzyme polymorphism in the VDR gene. METHODS: For this study, 98 patients who had been treated for BPH-related complaints and 61 convenience controls (predominantly bladder cancer patients) were recruited from the outpatient clinic. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. Means as well as odds ratios (ORs) with 95% confidence intervals (CI) were calculated using SPSS software. RESULTS: The mean number of CAG repeats in the AR gene in patients and controls was found to be similar: 21.8 (SD = 2.8) and 21.9 (SD = 2.9), respectively. In the subgroup of patients with a prostate volume of at least 50 cm(3), the mean number of repeats was 21.5 (SD = 2.6). The OR for BPH for individuals with homozygous presence of the VDR TaqI restriction fragment length polymorphism (RFLP) (tt) versus individuals with homozygous absence (TT) or heterozygotes (Tt) was found to be 1.0 (95% CI 0.4-2.4). For individuals with a prostate volume of at least 50 cm(3), the OR was 1.2 (95% CI 0.5-3. 2). CONCLUSION: Unlike earlier observations in prostate cancer, we did not find an association between the CAG repeat polymorphism in the AR gene and the TaqI RFLP polymorphism in the VDR gene and the risk of BPH.     

Polymorphisms in the vitamin D receptor gene and the risk of calcium nephrolithiasis in children

OBJECTIVE: Polymorphism in the Vitamin D Receptor (VDR) gene has recently been reported to be associated with calcium metabolism disorders. This study was conducted to investigate the association of VDR gene polymorphism with the risk of calcium nephrolithiasis. METHODS: We investigated the VDR ApaI, BsmI and TaqI polymorphisms, in relation to serum calcium, phosphate, intact parathyroid hormone and 1.25(OH)(2)D(3) in 64 hypercalciuric stone-forming children and 90 healthy children. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. RESULTS: The frequency of ApaI AA genotype was significantly higher in the children with calcium nephrolithiasis than the controls (chi(2)=9.5; p=0.008). The distribution of BsmI and TaqI genotypes in stone-forming patients was similar to those in the control group. There was a significant association between TaqI TT genotype and the strength of the family history. The patients with TT genotype were observed to have a 8 times more risk than patients with Tt/tt genotype for recurrent stone episodes (OR 8, 95%CI 1.61-39.6). CONCLUSION: VDR genotype determination may provide a tool to identify individuals who are at a risk for calcium nephrolithiasis.     

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population

PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.     

Association of vitamin D receptor gene polymorphism with urolithiasis

PURPOSE: Recent studies suggest that allelic variations of the vitamin D receptor (VDR) gene can influence calcium absorption and excretion. Therefore, we studied the association of VDR gene polymorphism with urolithiasis. SUBJECTS AND METHODS: We studied 83 patients with urinary stones and 83 controls. Patients were scored for certain clinical characteristics, including long axis diameter of the largest stone (1 point-less than 10 mm. and 2-10 mm. or greater), number of stones (1 point-1 and 2-multiple) and history of calcium stone disease (1 point-absent and 2-present). They were classified into 3 groups according to the total score, including low-3, intermediate-4 or 5 and high-6 points. The 2 VDR gene polymorphisms TaqI and ApaI were detected by polymerase chain reaction-restriction fragment length polymorphism and their relationships with the urinary calcium level were examined. RESULTS: The incidence of TaqI Tt and tt genotypes was significantly higher in the high score group than in controls. The TaqI t allele was associated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients with the Tt and tt genotypes was also higher than in those with the TT genotype. The rate of the ApaI genotype was not different in the high score group and controls. CONCLUSIONS: The TaqI t allele of the VDR gene may be a risk factor for severe stone disease and recurrent stones.     

维生素D受体基因多态性与白癜风的相关性研究

目的：探讨维生素D受体基因多态性与白癜风的相关性。方法：采用聚合酶链反应和限制性片段长度多态性方法，对749例白癜风患者和763例健康人的维生素D受体基因型进行分析。结果：白癜风患者维生素D受体BsmI、ApaI、TaqI位点基因型的分布与正常对照组相比有显著性差异，bb、aa、tt基因型在白癜风患者中频率较高，FokI位点基因型的分布与对照组无明显差异。单倍体型分析表明FokI位点和BsmI位点，BsmI位点和ApaI位点，BsmI和TaqI位点，ApaI位点和TaqI位点之间存在较强的连锁不平衡，白癜风患者中fbAT、FbAT和FbaT单倍体型的频率显著高于对照组。结论：维生素D受体基因多态性与白癜风有明显的相关性。携带维生素D受体基因纯合子bb、aa或tt基因型可能会增加对白癜风的易感性。     

Familial calcium stone disease: TaqI polymorphism and the vitamin D receptor.

BACKGROUND AND OBJECTIVE: Calcium nephrolithiasis has a strong familial component. However, to date, no specific genetic abnormality has been identified. Allelic variation in the vitamin D receptor (VDR) gene has been suggested as a partial explanation of differential calcium absorption or excretion in these patients. Polymorphism of this gene has been associated with altered vitamin D activity and has been implicated in osteoporosis and prostate cancer. We propose that a similar association may be found between familial hypercalciuric stone disease and the VDR. SUBJECTS AND METHODS: Genomic DNA was isolated from 37 controls and 19 patients with hypercalciuria (> 250 mg/24 hours) and a family history of nephrolithiasis. A 740-basepair segment of the VDR gene was amplified by polymerase chain reaction, digested with TaqI endonuclease, and resolved by gel electrophoresis. Alleles were classified as "T" if only one TaqI site was present and "t" if two were present. A simplified strength of family history score (FHS) was computed by adding 2 and 1 points, respectively, for each first- and second-degree relative affected by stone disease. RESULTS: No difference in allelic or genotypic frequencies between the study and control groups was present. In the stone group, a significant association was found between the strength of the family history and the TT genotype. Patients with this genotype had an average FHS of 4.0, whereas the mean FHS for the Tt and tt genotypes was 2.0 and 1.8, respectively (P < 0.05). Nonsignificant trends of the TT genotype toward a higher number of stone episodes (19 v 13 and 3) and higher 24-hour urine calcium excretion (408 v 297 and 353 mg) were also noted in the study group. CONCLUSION: The results suggest that the TT genotype is associated with more aggressive stone disease, both within families and with respect to recurrence. Quantifying the risk of calcium stone disease through DNA markers has potential application in determining the risk of a patient's family members for nephrolithiasis or a patient's risk of recurrence. This information may have therapeutic implications with regard to the rigor of medical therapy and frequency of follow-up.     

维生素D受体基因Taq Ⅰ位点多态性与亚洲男性前列腺癌易感性的Meta分析

目的探讨维生素D受体（VDR）基因Taq Ⅰ位点多态性与亚洲男性前列腺癌易感性的关系。方法检索PubMed、中国知网、万方数据库、维普中文科技期刊,获取VDR基因Taq I位点多态性与亚洲男性前列腺癌易感性的病例-对照研究。以前列腺癌组与对照组人群基因型分布的OR值为效应指标,采用固定或随机效应模型进行合并分析,并进行偏倚评估,应用STATA10.0软件进行统计学处理。结果共纳入文献10篇,研究10项,累计前列腺癌病例1 141例,对照1 685例。与等位基因T相比,C等位基因合并的OR（95%CI）为0.81（0.70~0.94）;与野生基因型TT相比,CT和CC＋CT基因型合并的OR（95%CI）分别为0.86（0.74~1.01）和0.84（0.73~0.97）。结论 VDR基因Taq Ⅰ位点变异可能会降低亚洲男性个体患前列腺癌的危险性。     

Human kallikrein-2 gene polymorphism is associated with the occurrence of prostate cancer

PURPOSE: Human glandular kallikrein, which is encoded by the human kallikrein-2 (KLK2) gene, is significantly associated with the occurrence of prostate cancer (PCa). We tested the association between a functional C748T polymorphism of the KLK2 gene and the occurrence of PCa. MATERIALS AND METHODS: Peripheral venous blood samples were obtained from 254 patients with PCa and 168 controls with benign prostatic hyperplasia. All control subjects had normal serum prostate specific antigen and proved to be free from malignancy on pathological examination of resected prostatic tissues. Serum prostate specific antigen, testosterone, Gleason score, clinical and pathological stage, tumor and prostate volume of the patients were investigated. The KLK2 gene polymorphism was determined by the polymerase chain reaction based restriction fragment length polymorphism method. RESULTS: The PCa group had a younger mean age +/- SEM (73.0 +/- 0.5 vs 74.7 +/- 0.5 years, p = 0.010) and higher C allele frequency (82.1% vs 74.7%, p = 0.010) than the control group. The frequency of the CC, CT and TT genotypes was 65.7%, 32.7% and 1.6% in patients with PCa, and 56.0%, 37.5% and 6.5%, respectively, in controls (p = 0.010). C allele carriers (CC and CT genotypes) were at significantly higher risk for PCa than TT homozygous subjects (p = 0.002). CC homozygous subjects were at significantly higher risk for PCa than T allele carriers (CT and TT genotypes) (p = 0.043). The PCa subgroup of patients with pathologically proved, localized PCa also had a higher frequency of the C allele (87.5% vs 74.7%, p = 0.026) and CC genotypes (78.7% vs 56.0%, p = 0.019) than controls. CONCLUSIONS: Our results suggest that the C allele of the functional C748T polymorphism of KLK2 may increase the risk of PCa.     

A systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk

PURPOSE: Polymorphisms in the vitamin D receptor gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the associations between specific vitamin D receptor polymorphisms and prostate cancer risk have yielded inconsistent results. MATERIALS AND METHODS: We performed a meta-analysis of 26 studies evaluating the association between vitamin D receptor TaqI, poly(A), BsmI, ApaI, and/or FokI polymorphisms, and prostate cancer risk. RESULTS: The studies were heterogeneous in terms of study design, selection of cases and controls, and racial composition. Random effects models were used to estimate the pooled OR and 95% CI of each vitamin D receptor polymorphism under codominant, additive, dominant and recessive genetic models. Overall we did not find evidence to support an association between any of the vitamin D receptor polymorphisms and the risk of prostate cancer. For TaqI, which is the most studied vitamin D receptor polymorphism with 18 studies (total of 2,727 cases and 3,685 controls), the pooled OR was 1.00 (95% CI 0.85 to 1.18) for the Tt vs TT genotypes, 0.94 (95% CI 0.78 to 1.13) for the tt vs TT genotypes and 0.89 (95% CI 0.71 to 1.10) for the recessive model (tt vs Tt plus TT). ORs for the poly(A) microsatellite, BsmI, ApaI and FokI polymorphisms were similar. CONCLUSIONS: The results of this meta-analysis suggest that the vitamin D receptor TaqI, poly(A), BsmI, ApaI and FokI polymorphisms are not related to prostate cancer risk.     

Impact of vitamin D receptor gene polymorphisms on clinical outcomes of HLA-matched sibling hematopoietic stem cell transplantation

We hypothesized that polymorphisms of the vitamin D receptor (VDR) gene might affect clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). Three VDR gene polymorphisms (BsmI G>A, ApaI G>T, and TaqI T>C) were genotyped in 147 patients who underwent HLA-matched sibling allogeneic HSCT. Frequencies of infection, graft-vs.-host disease (GVHD), overall survival (OS), and disease-free survival (DFS) were compared according to genotypes and haplotypes. Infection and acute GVHD had trends to be less frequent in patients with ApaI TT genotype than non-TT genotypes (p = 0.061 and p = 0.059, respectively). For TaqI genotypes, there were no statistical differences in frequency of infection and acute GVHD (p = 0.84 and p = 0.30, respectively), but TC genotype was associated with longer OS and DFS than TT genotype (p = 0.022 and p = 0.038, respectively). In the ApaI-TaqI haplotype analysis, patients with TC haplotype had significantly longer OS and DFS than those without TC haplotype (p = 0.022 and p = 0.038, respectively). In multivariable analysis, TaqI genotype and ApaI-TaqI haplotype of recipients were independent prognostic factors for both OS and DFS. This study suggests that the genotype and haplotype of VDR in recipient might be associated with clinical outcome of sibling HLA-matched HSCT.     

Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population

AIM: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)(2)D(3) and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. METHODS: To analyze risk of RCC depending on VDR polymorphism, a case-control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. RESULTS: Significant differences in the ApaI genotype were observed between RCC patients and controls (chi(2) = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21-5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). CONCLUSION: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted.     

Vitamin D receptor gene polymorphism in familial prostate cancer in a Japanese population

AIM: Vitamin D acts as an antiproliferative agent against prostate cells. Epidemiological study has shown that a low level of serum vitamin D concentration is a risk factor for prostate cancer. Vitamin D acts via vitamin D receptor (VDR), and an association of genetic polymorphisms of the VDR gene has been reported. In the current study, we examined the association of VDR gene polymorphisms with familial prostate cancer in a Japanese population. METHODS: We performed a case-control study consisting of 81 familial prostate cancer cases and 105 normal control subjects. Three genetic polymorphisms (BsmI, ApaI and TaqI) in the VDR gene were examined by the restriction fragment restriction length polymorphism method. RESULTS: Overall, there was no significant association of the VDR gene polymorphisms with familial prostate cancer risk in the cases and control subjects. However, a weak association between BsmI or TaqI genotypes and cancer risk was observed in subjects under 70 years of age. Stratification of cases by clinical stage or pathological grade did not show significant association between the VDR gene polymorphisms and prostate cancer risk. CONCLUSION: In the present study, we could not confirm any significant association between VDR gene polymorphisms with familial prostate cancer risk in a Japanese population. Further large-scale case-control studies are warranted to confirm the importance of VDR gene polymorphisms in familial prostate cancer.     

Incidence and risk factors of clinical characteristics, tacrolimus pharmacokinetics, and related genomic polymorphisms for posttransplant diabetes mellitus in the early stage of renal transplant recipients

PURPOSE: Posttransplant diabetes mellitus (PTDM) is an important complication in a tacrolimus (TAC)-based immunosuppressive regimen. The present study investigated the incidence, clinical risk factors, TAC pharmacokinetics (PK), and genomic polymorphisms related to TAC-PK or diabetes mellitus (DM) under the TAC-based immunosuppressive protocol. PATIENTS AND METHODS: Seventy-one nondiabetic renal allograft recipients transplanted from February 1998 to March 2004 were studied. Patients with over 6.5 mg/dL of hemoglobin A1c on sequential blood samples or requiring insulin or oral antidiabetic agents around 6 months after transplantation were diagnosed as having PTDM. RESULTS: Six months after transplantation, 10 recipients (14.1%) developed PTDM. The positive risk factors were age (P = .003) and body mass index (P = .035). There were no significant differences in gender distribution, pretransplant dialysis period, dialysis modality, acute rejection rate, total steroid doses, TAC-PK, or its related genomic polymorphisms between the two groups. In the DM-related polymorphisms, the frequency of PTDM was significant higher in patients with the VDR TaqI tt or Tt genotype than in those with the TT genotype (P = .013). After a multivariate analysis, age over 50 years (P = .007, odds ratio 8.92) and the presence of VDR TaqI t allele (P = .043, odds ratio 6.71) were correlated with the development of PTDM. CONCLUSION: The incidence of PTDM in our series was 14.1%. Age over 50 years was a risk factor. The presence of VDR TaqI t allele might be a risk for PTDM. An association between TAC-PK and development of PTDM was not observed.     

N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men

BACKGROUND: The purpose of this study was to determine the frequency of a polymorphism of the candidate metabolic enzyme N-acetyltransferase-2 (NAT2) in Japanese prostate cancer patients and Japanese non-cancer controls, in order to determine if an association exists between NAT2 genotype and the occurrence, clinical stage and grade of prostate cancer. METHODS: In the present case-control study, 111 patients with prostate cancer and 152 controls were genotyped for the NAT2 polymorphism using the polymerase chain reaction-based restriction fragment length polymorphism method. The NAT2 genotypes (slow or rapid acetylator genotype) were determined by the combination of three known NAT2 mutant alleles (M1, M2, M3) and the wild-type allele. RESULTS: The NAT2 slow acetylator genotype was statistically higher among prostate cancer patients (17.1%) compared with controls (8.6%) (Odds ration (OR) = 2.21; 95% confidence interval (CI), 1.04-4.69; P = 0.0289). In addition, there was a statistically increased risk of prostate cancer among smokers with the NAT2 slow genotype (OR = 3.78: 95% CI, 1.48-9.66; P = 0.0041). Furthermore, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with locally advanced and metastatic disease (22.7%) compared with controls (8.6%) (OR = 3.14; 95% CI, 1.40-7.06; P = 0.0051). Lastly, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with high-grade tumors (31.4%) compared with controls (8.6%) (OR = 4.90; 95% CI, 1.97-12.20; P = 0.0010). CONCLUSION: These data demonstrate that the NAT2 slow acetylator genotype plays an important role in determining the risk of developing prostate cancer in Japanese men and is also associated with more clinically advanced and pathologically aggressive disease. Furthermore, a possible interaction between the NAT2 slow acetylator genotype and smoking status was suggested.     

Preferential humoral immune response in prostate cancer to cellular proteins p90 and p62 in a panel of tumor-associated antigens

BACKGROUND: Cytoplasmic p90 autoantigen was recently cloned from a cDNA expression library using serum antibody from a cancer patient. The humoral immune response to p90 in prostate cancer and benign prostatic hyperplasia (BPH) was examined. METHODS: An antigenic fragment of recombinant p90 protein and several other tumor-associated antigens (TAAs) were used in ELISA and Western blotting to detect antibodies in sera from patients with prostate cancer, BPH, and other controls. RESULTS: Autoantibodies to p90 were detected in 30.8% of 133 prostate cancer patients versus 1.5% in 68 BPH patients. When a selected panel of six TAAs including p90 were used for immunoscreening, the cumulative positive reactions in prostate cancer sera reached 92.5%, significantly higher than in BPH and other control sera. Antibodies to p90 showed the highest frequency in prostate cancer (30.8%), followed by antibodies to p62 (22.6%). CONCLUSIONS: A panel of six selected TAAs was shown to have high sensitivity and specificity as immunodiagnostic markers in prostate cancer.     

Association of Vitamin D Receptor Genetic Polymorphisms With Nephrolithiasis and End-Stage Renal Disease: A Meta-Analysis

BackgroundOur objective was to evaluate the association between vitamin D receptor (VDR) BsmI, FokI, TaqI, and ApaI gene polymorphisms and the risk of renal disease. A meta?analysis was conducted to determine the correlation between these VDR gene polymorphisms and the renal disease.MethodsMeta-analysis was carried out to clarify the association of BsmI (2467 cases and 2651 controls), FokI (2460 cases and 3085 controls), TaqI (3181cases and 3713 controls), and ApaI (2512 cases and 3091 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN), and end-stage renal disease (ESRD).ResultsThe VDR BsmI C allele, under the allele contrast random effect model, was associated with renal diseases calculated for ESRD. Subgroup analysis revealed association of VDR FokI polymorphism with ESRD and no association with NL and DN. The VDR TaqI C allele, under the allele contrast fixed effect model, was associated with renal diseases calculated collectively for DN, ESRD, and NL. Cochran's Q test showed no evidence of heterogeneity for TaqI and ApaI polymorphisms and showed a significant heterogeneity for BsmI and FokI polymorphisms.ConclusionsThis meta-analysis identifies BsmI, FokI, TaqI and ApaI polymorphisms of the VDR gene as risk factors for renal diseases.     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.