前列腺癌发生风险与CYP3A5基因多态性的关系

目的 探讨CYP3A5基因多态性与前列腺癌发生风险和病理特点的关系。方法 采用限制性片段多态性分析法对356例前列腺癌患者和306个男性对照中CYP3A5基因第3内含子多态性进行了研究。结果 在前列腺癌和对照组之间CYP3A5基因型分布差异无显著性(P=0．063)，但两组间CYP3A5*1等位基因的分布差异存在显著性(P=0．025)；与携带CYP3A5*3*3基因型者相比，携带CYP3A5*1等位基因的男性患前列腺癌的风险降低了30％(P=0．026)。在不同分期和分级的前列腺癌患者之间CYP3A5基因型分布差异无显著性(P=0．904和0．986)。结论 CYP3A5基因中的CYP3A5*1等位基因可能与前列腺癌的患病风险降低有关。     

Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese

OBJECTIVE: Recent studies have demonstrated an association between vitamin D receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of data regarding the association of VDR genotype with benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in order to determine if an association exists between VDR genotype and the risk of developing prostate cancer and BPH as well as disease severity. METHODS: 110 prostate cancer patients, 83 BPH patients and 90 male age-matched controls were genotyped for a previously described TaqI restriction fragment length polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into T allele or t allele according to the absence or presence of a TaqI restriction site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of the genotype tt was higher in the control group (6.7%) compared to patients with prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant. However, the frequency of the genotype TT was significantly higher among prostate cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1) compared to controls (p = 0.001). In addition, the genotype TT was significantly higher among prostate cancer patients with a high Gleason grade of tumor (grade 5) compared to controls (p = 0.0001). In addition, the genotype TT was statistically higher in BPH patients with high prostate volume (volume >50 cm(3)) compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR genotype plays an important role in determining the risk of more advanced and aggressive prostate cancer as well as prostatic enlargement in Japanese men.     

HPC2/ELAC2 polymorphism associated with Japanese sporadic prostate cancer

BACKGROUND: HPC2/ELAC2 gene was identified by linkage analysis from familial prostate cancer (Pca) patients in USA. To determine the association of HPC2/ELAC2 gene with Japanese sporadic Pca, we performed a case-control study focused on two missense polymorphisms. METHODS: We genotyped the two polymorphic sites of Ser217Leu and Ala541Thr in sporadic Japanese Pca patients (n = 285) and matched controls (n = 233). Controls were unrelated Japanese outpatients who had no history of any cancer and normal PSA level (less than 4.0 ng/ml). Statistical analyses were performed by Mann-Whitney's U-test, Fisher's exact test, and logistic regression analysis. RESULTS: We observed a significantly higher frequency of the Thr allele at 541 polymorphic site in Pca patients (8.4%) compared to the control group (2.1%) (P = 0.0030, Odds Ratio (OR) = 4.02, 95% CI = 1.50-10.8). However, this SNP does not correlate with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. No association was identified at Ser217Leu polymorphic site. CONCLUSIONS: Our results indicate that Thr allele at 541 in HPC2/ELAC2 has strong significance in the predisposition of sporadic Pca in Japan. This polymorphism can be useful to predict the personal Pca risk, which lead the effective screening of Pca.     

Genetic variants of the cytochrome P450 and glutathione S-transferase associated with risk of bladder cancer in a south-eastern Chinese population

Objective:   To evaluate the association between genetic polymorphisms of CYP2E1 RsaI and GSTM1 and development of bladder cancer in a south-eastern Han Chinese population.
Methods:   We hypothesized that the CYP2E1 -1019T>A and GSTM1 polymorphisms were associated with risk of bladder cancer. In a hospital-based case-control study of 202 case patients with newly diagnosed bladder transitional cell carcinoma and 272 cancer-free controls frequency-matched by the age and sex, we genotyped these two polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism method.
Results:   We found that the GSTM1 null genotype was associated with an increased risk of bladder cancer (adjusted odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.17–2.56) compared with those with the non-null genotype, but the CYP2E1 -1019T>A polymorphisms did not show any association. In the stratification analysis of the GSTM1 polymorphism, we found that the increased risk was more pronounced among subgroups aged ≤60 years (OR = 2.02, 95% CI = 1.08–3.77), smokers (OR = 1.94, 95% CI = 1.11–3.38) and non-drinkers (OR = 3.86, 95% CI = 1.28–11.60).
Conclusion:   GSTM1 polymorphism (but not CYP2E1 RsaI polymorphism) appears to contribute to the etiology of bladder cancer in a south-eastern Chinese population.     

代谢酶基因多态性与前列腺癌易感性的关系

目的 :探讨CYP1A1、NAT2基因多态性与前列腺癌易感性的关系。　方法 :应用PCR RFLP、ASA和自动实时荧光定量分析技术 ,分析 5 8例前列腺癌病人和 112例健康对照者CYP1A1和NAT2基因 4个位点的多态性 ,比较前列腺癌病人与对照组间频率差异。　结果 :前列腺癌组Ile Val多态位点各等位基因和基因型频率与对照组比较差异有显著性 (P <0 .0 5 ) ,其中等位基因G和GG基因型使患前列腺癌的危险度分别提高了 1.5 9倍 (P <0 .0 5 )和 3.0 6倍 (P <0 .0 5 ) ;前列腺癌组MspI多态位点各等位基因和基因型频率与对照组比较差异无显著性 (P>0 .0 5 )。前列腺癌组NAT2慢乙酰化基因型频率与对照组比较差异无显著性 (P >0 .0 5 )。　结论 :CYP1A1Ile Val基因多态与前列腺癌的发生可能有关 ,MspI基因多态和NAT2慢乙酰化基因型与前列腺癌的发生可能无关     

Sequence variants in the human 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) gene are not associated with prostate cancer risk

BACKGROUND: 1,25-dihydroxyvitamin D(3) has been shown to have antiproliferative properties on normal and neoplastic prostatic cells. 25-hydroxyvitamin D(3) 1-alpha-hydroxylase, the enzyme that catalyzes the final step of vitamin D synthesis, converting 25-hydroxyvitamin D(3) to 1,25-dihydroxyvitamin D(3), is expressed in the prostate. METHODS: The human 25-hydroxyvitamin D(3) 1-alpha-hydroxylase gene (CYP27B1) was resequenced in a case/control panel consisting of 64 individuals (48 Caucasians and 16 African Americans), with equal numbers of hereditary prostate cancer cases, sporadic cases, and unaffected controls. Three frequent single nucleotide polymorphisms (SNPs) were genotyped in 245 prostate cancer cases and 222 controls. RESULTS: Six noncoding SNPs were identified in the CYP27B1 gene. No significant difference was found in allele and genotype frequencies between sporadic cases and unaffected controls for the three genotyped SNPs. CONCLUSION: This study suggests that the CYP27B1 gene does not play a major role as a prostate cancer susceptibility gene.     

雌激素代谢酶CYP17、CYP19单核苷多态性与乳腺癌易感性的相关性分析

目的 初步探讨雌激素代谢酶CYP17和CYP19单核苷多态性与乳腺癌易感性的相关性.方法 采用聚合酶链反应-限制性片段长度多态性及短串联重复多态性方法,检测213例乳腺癌患者和430例正常对照CYP17、CYP19单核苷多态性分布.结果 乳腺癌患者雌激素代谢酶CYP17 A2/A2基因型频率为6.7%,高于对照组的2.4%(P＜0.05),CYP17变异等位基因A2病例组的频率为16.2%,亦明显高于对照组的10.6%(P＜0.05);乳腺癌患者雌激素代谢酶CYP19(TTTA)10等位基因病例组的频率为12.4%,对照组为8.2%,差异有统计学意义(P＜0.05).结论 CYP17单核苷多态性与乳腺癌易感性相关,A2/A2基因型增加乳腺癌风险;CYP19单核苷多态性与乳腺癌易感性亦相关,CYP19(TTTA)10等位基因变异升高与乳腺癌易感性高度相关.     

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.     

脂氧酶12 编码区遗传变异与胃癌发病的关系

目的：探讨位于脂氧酶12（LOX12）基因编码区Arg261Gln单核苷酸多态与胃癌发病风险的关系。方法：用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）方法检测148例胃癌患者和148例无肿瘤正常对照人群的LOX12的基因型,并以Logistic回归模型计算各基因型与胃癌发病风险的关系。结果：LOX12 Arg261Gln等位基因频率在胃癌组中（0.544）高于正常组（0.443）。与Arg/Arg基因型携带者相比,Gln/Gln基因型携带者发生胃癌的风险增加（OR=2.26,95%CI=1.15~4.46,P=0.018）,而杂合基因型Arg/Gln不增加胃癌发病风险（OR=1.37,95%CI=0.77~2.44,P=0.284）。结论：LOX12编码区Arg261Gln遗传变异可能是胃癌发病的重要遗传易感因素。     

SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness

BACKGROUND: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles. RESULTS: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.     

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

Objectives:   To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer.
Methods:   One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease.
Results:   Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer ( P  < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters.
Conclusions:   The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.     

中国维吾尔族男性CYP17基因多态性与前列腺癌发生的关系

目的:探讨维吾尔族男性CYP17基因多态性与前列腺癌发生危险性的关系。方法:收集31例前列腺癌患者和104例对照组的血液标本并提取DNA,设计引物,通过PCR扩增包括基因多态位点的片段,用限制性内切酶M spA1 I进行酶切,产物在2%琼脂糖凝胶上电泳,确定CYP17基因的3种基因型,即A1/A1、A1/A2、A2/A2,并经测序证实,同时测定血清标本中前列腺特异性抗原(PSA)含量。结果:基因型A1/A2、A2/A2频数与A1/A1比较,A1/A2和A2/A2在前列腺癌中的频数与对照组相比,其OR值分别为1.49和2.87,P值分别为0.321和0.052,肿瘤组3种基因型间的PSA值差异无显著性。而对照组中A1/A2组的PSA值高于A1/A1组,但差异无显著性(P=0.062),而A2/A2组显著高于A1/A1组(P=0.018)。结论:A2/A2基因型在前列腺癌中的频数有显著高于对照组的趋势,提示A2/A2基因型可能与维吾尔族男性前列腺癌发生危险性之间有密切关系,而对照组中A2/A2基因型组的PSA值的显著增高也支持了这一观点。     

Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility

BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.     

Perineural invasion is a prognostic factor for biochemical failure after radical prostatectomy

Objectives:   To identify the prognostic significance of lymphovascular invasion (LVI) and perineural invasion (PNI) in patients undergoing radical prostatectomy for prostate cancer.
Methods:   Overall, 237 patients who had undergone radical prostatectomy for prostate cancer between 1995 and 2004 were analyzed for all clinical and pathological factors. The influence of these two pathological features on biochemical failure-free survival was evaluated by univariate and multivariate analysis.
Results:   Lymphovascular and perineural invasion were identified in 41 (17.2%) and 100 (42.0%) patients, respectively. LVI and PNI were significantly associated with the preoperative prostate-specific antigen (PSA) level, a higher PSA density, a higher pathological stage, a higher Gleason score, a higher frequency of extracapsular extension, a higher frequency of seminal vesicle invasion, and a higher frequency of a positive resection margin. Positive resection margins ( P  = 0.001) and perineural invasion ( P  = 0.011) were identified as independent factors associated with biochemical failure-free survival by the multivariate analysis.
Conclusions:   In this series, PNI was associated with established parameters of biologically aggressive disease, and was an important prognostic factor for biochemical failure-free survival in patients undergoing radical prostatectomy. This finding supports routine evaluation of the PNI status in radical prostatectomy specimens and suggests that patients with PNI should be more closely followed after surgery.     

Further evidence for null association of phenol sulfotransferase SULT1A1 polymorphism with prostate cancer risk: a case–control study of familial prostate cancer in a Japanese population

Sulfation is a key pathway in xenobiotic metabolism and chemical defense, and phenol sulfotransferase SULT1A1 plays a central role in this reaction. Genetic polymorphism of the SULT1A1 gene, SULT1A1, was reported to be associated with risks of several cancers; however, one study showed no significant relation between SULT1A1 genotype with prostate cancer risk. The present study was conducted to confirm the association of a G638A polymorphism, Arg213His, in SULT1A1 with familial prostate cancer risk in a Japanese population. A case–control study consisting of 126 cases and 119 controls was performed. In controls, GG, GA, and AA genotypes were observed in 85 (71.4%), 32 (26.9%), and 2 (1.7%), respectively; whereas, GG, GA, and AA genotypes were observed in 94 (74.6%), 32 (25.4%), and 0 cases, respectively. No significant differences were found in genotypic frequencies among cases and controls. Furthermore, stratification of cases according to clinical stages (localized or metastatic), pathological grades (Gleason score <7, or >7), age at diagnosis (<70 years or >70) and the number of affected relatives (2 or >2) did not show any significant differences among categories. These findings suggested that genetic polymorphism of SULT1A1 might not be involved in genetic susceptibility to prostate cancer.     

Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score

BACKGROUND: Although, a functional rationale for influence of polymorphism D85Y in gene UGT2B15 on prostate cancer (PCa) exists (different V(max) of enzyme), conflicting results have been reported. METHODS: DNA from 178 controls and 206 PCa patients with known Gleason score were genotyped using a newly developed RFLP assay, which allowed the detection of both alleles in an individual after single PCR amplification. RESULTS: Controls: 16% DD, 52% DY; PCa patients: 23% DD, 49% DY. Subgroups of PCa: well differentiated: 11% DD, 37% DY; moderately differentiated: 22% DD, 50% DY; poorly differentiated: 34% DD, 50% DY. Correlation was confirmed between Gleason score and number of D alleles (P = 0.018) and persisted after age adjustment. When comparing controls to patients with a Gleason score of 7 or more, difference for the frequency of homozygosity DD was significant between the groups (P = 0.032, OR = 2.04). CONCLUSIONS: Polymorphism D85Y in gene UGT2B15 correlates with differentiation of PCa.     

Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer

BACKGROUND: Circulating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH-beta protein, LH-betaV, exists in up to 40% of Caucasians and is more bioactive than the wild-type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion. METHODS: We determined the frequency of the LH-betaV polymorphism (two linked polymorphisms: Trp(8) --> Arg and Ile(15) --> Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population-based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer. RESULTS: A higher frequency of this variant genotype (LH-betaV: Arg(8)/Thr(15)) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH-beta genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96-1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86-02.07). Surgical cases showed a slightly stronger association for the variant LH-beta genotype compared to non-surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade. CONCLUSIONS: These data are consistent with the hypothesis that the LH-beta variant is a weak risk factor for prostate cancer.     

Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate cancer

BACKGROUND: Cytochrome P450s (CYPs) influence the biological effects of carcinogens, drugs and hormones including testosterones. Among them, Cytochrome P450 2B6 (CYP2B6) plays a critical role in the deactivation of testosterone. In the present study, we examined CYP2B6 expression in human prostate tissues and prostate cancer. METHODS: Immunohistochemical analysis was performed in 98 benign and 106 malignant prostate tissues and patients' charts were reviewed for clinical, pathologic and survival data. We also investigated whether stable expression of CYP2B6 in LNCaP (human prostate cancer cell line) influences cellular proliferation. RESULTS: CYP2B6 was abundantly expressed in the normal epithelial cells compared to the prostate cancer cells. Significant immunostaining of CYP2B6 was found in 75 of 106 samples (71%), in the cytoplasm of cancerous tissue samples. CYP2B6 immunoreactivity was inversely correlated with high Gleason score (P < 0.001). Decreased immunoreactivity of CYP2B6 significantly correlated with poor prognosis (P < 0.0001). Univariate and multivariate hazard analyses revealed a significant correlation of decreased CYP2B6 expression with poor cancer-specific survival (P = 0.0028 and 0.0142, respectively). Furthermore, overexpression of CYP2B6 in LNCaP cells significantly decreased testosterone-induced proliferation. CONCLUSIONS: These results demonstrated that decreased expression of CYP2B6 might play a role in the development of prostate cancer, and be useful as the prognostic predictor for human prostate cancer.     

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.