China ; epidemiology ; Humans ; Male ; Prostatic Neoplasms ; epidemiology ; genetics ; surgery

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.
China/epidemiology* ; Humans ; Male ; PTEN Phosphohydrolase/genetics* ; Prognosis ; Prostatic Neoplasms ; Retrospective Studies

OBJECTIVETo investigate the association of the risk of prostate cancer (PCa) with the polymorphism of the CYP2E1 gene, smoking and drinking, and to explore the joint role of genes and living habits in PCa pathogenesis.

METHODSWe conducted a case-control study on 109 PCa patients and 202 age-matched non-PCa male controls, and detected the polymorphisms of CYP2E1 Rsa I and Pst I sites by PCR-RFLP using DNA from peripheral blood lymphocytes.

RESULTSThe history of deep smoking (OR = 2.29, 95% CI: 1.28 - 4.09) or heavy smoking (OR = 1.81, 95% CI: 1.02 - 3.22) was a risk factor. The CYP2E1 C1/C1 genotype significantly increased the risk of PCa (OR = 1.71, 95% CI: 1.04 - 2.82) and apparently interacted with drinking (OR = 2.21, 95% CI: 1.06 - 4.59). Heavy smokers with the C1/C1 genotype showed an increased risk of PCa (OR = 2.80, 95% CI: 1.20 - 6.56), as compared with non-smokers carrying the genotype of C1/C2 or C2/C2.

CONCLUSIONThe risk of PCa obviously increases in individuals with both the CYP2E1 C1/C1 genotype and the habit of smoking or drinking, and it has a significant positive correlation with the dose of tobacco exposure.

Aged ; Alcohol Drinking ; epidemiology ; genetics ; Case-Control Studies ; China ; epidemiology ; Cytochrome P-450 CYP2E1 ; genetics ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Prostatic Neoplasms ; epidemiology ; genetics ; Smoking ; epidemiology ; genetics

OBJECTIVETo explore the etiologic relationship of prostate cancer and environmental and genetic polymorphism in southern China

METHODSA hospital-based and 1:1 matched case-control study was conducted. A total of 142 matched pairs of subjects were investigated in this study. The blood samples were collected from 85 cases of prostate cancer and 82 controls of other diseases after informing consent. The CYP1A1, CYP17 and AR genes were analyzed by using the method of PCR, PCR-RFLP. The data were analyzed with conditional logistic regression model.

RESULTSAn increased risk of prostate cancer development was observed with the early first spermatorrhea (age < 18) (OR = 2.90, 95% CI: 1.76 - 4.80), early first sexual intercourse (age < or = 24) (OR = 2.38, 95% CI: 1.14 - 4.96), frequent sexual intercourse before 35 year old (OR = 1.80, 95% CI: 1.19 - 2.70), family history of cancer (OR = 2.70, 95% CI: 1.31 - 5.58), more intake of pork (OR =2.27, 95% CI: 1.38 - 3.70). Factors in lowing the risks were the fruit intake and drinking of green tea by OR value at 0.25 (95% CI: 0.08 - 0.75) and 0.52 (95% CI: 0.28 -0.96) respectively. CYP17 A1/A2 and CYP17 A2/A2 genotypes were related with a high risk of prostate cancer and OR values of 1.78 (95% CI: 0.70 - 4.53) and 2.57 (95% CI: 0.91 - 7.25) respectively. Study also showed that there was an interaction between CYP17 polymorphisms and early first spermatorrhea and family cancer history related to the risk of prostate cancer with OR value at 13.35 (95% CI: 1.58 - 113.00) and 4.01 (95% CI: 1.22 - 13.17) respectively.

CONCLUSIONSexual intercourse, dietary intake and family cancer history should be related to prostate cancer occurrence. CYP17 polymorphism might be associated with a high risk of prostate cancer. It suggests that there are multiple environmental and genetic factors to the prostate cancer.

Aged ; Case-Control Studies ; China ; epidemiology ; Environmental Exposure ; Genotype ; Humans ; Male ; Middle Aged ; Promoter Regions, Genetic ; Prostatic Neoplasms ; epidemiology ; genetics ; Risk Factors ; Steroid 17-alpha-Hydroxylase ; genetics

AIMTo investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer (PCa) in men from Han, Southern China.

METHODSIn a case-control study of 207 patients with PCa and 235 cancer-free controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms (codons 194, 280 and 399) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method.

RESULTSAmong the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk (adjusted odd ratio [OR]: 1.67, 95% confident interval [CI]: 1.11-2.51), but the XRCC1 Arg194Trp variant allele had a 38% reduction in risk of PCa (adjusted OR: 0.62, 95% CI: 0.41-0.93). However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa (adjusted OR: 4.31; 95% CI: 1.24-14.99) than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers (adjusted OR: 2.04; 95% CI: 1.03-4.05).

CONCLUSIONThese results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.

Adenocarcinoma ; blood ; epidemiology ; genetics ; Aged ; China ; epidemiology ; DNA-Binding Proteins ; blood ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Odds Ratio ; Polymorphism, Restriction Fragment Length ; Prostatic Neoplasms ; blood ; epidemiology ; genetics ; Risk Factors ; Seroepidemiologic Studies ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo investigate the polymorphism in the promoter region of PCA3 gene and its relationship with risk of prostate cancer (PCa).

METHODSThe promoter region of PCA3 gene of the DNA of peripheral blood mononuclear cells was detected by sequence analysis in the 186 PCa and 141 BPH patients and 135 healthy control individuals. If the samples were detected with polymorphism of insection/deletion, clone sequence analysis was used with pBS-T carrier to verify it.

RESULTSThere were 5 polymorphisms. TAAA repeat times: 4, 5, 6, 7, 8, and 8 genotypes (TAAA 4/5, TAAA 4/6, TAAA 5/5, TAAA 5/6, TAAA 5/7, TAAA 5/8, TAAA 6/6, and TAAA 6/7) were detected in the promoter region of PCA3 gene. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. Unconditional logistic regression analysis models were used to analyze the relationship between different genotypes and cancer risks adjusted by sex and age. The type 11TAAA and ≥12TAAA was associated with higher relative risk for prostate cancer than the group ≤10TAAA [OR=1.74, 95% CI=1.06-2.87 (for type 11TAAA); OR=5.63, 95% CI=1.85-17.19 (for type ≥12TAAA)]. In the 186 PCa patients, there was 62.4% allele of PCA3 gene with AG/CA mutation found in the promoter 18-19 bp region of PCA3 gene and it had a close relation with the development of prostate cancer.

CONCLUSIONSShort tandem repeats are found in the promoter region of the PCA3 gene in PCa patients, and the increase of TAAA repeat sequences highly enhance the relative risk of prostate cancer development. The occurrence of such STR might be related to the mutations in their upstream loci.

Antigens, Neoplasm ; genetics ; metabolism ; Base Sequence ; Genes, Neoplasm ; physiology ; Genotype ; Humans ; Leukocytes, Mononuclear ; Male ; Microsatellite Repeats ; Mutation ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Prostatic Neoplasms ; epidemiology ; genetics ; Risk

OBJECTIVEProstate cancer (PCa) has the highest incidence among male malignancies in Western industrialized countries and, as a most common malignant disease in urology, its incidence has been increasing in recent years in Chinese men. This study was to investigate the risk loci associated with PCa susceptibility in Han Chinese by analyzing single nucleotide polymorphisms (SNP).

METHODSWe collected peripheral blood samples from 1 667 PCa patients and 1 525 healthy men, and detected 40 loci associated with PCa susceptibility by analyzing SNPs using Sequenom technology.

RESULTSOf the 40 known loci, 16 were confirmed to be significantly associated with PCa susceptibility (P < 0.05). The loci 1, 2 and 5 at 8q24, 10q11 and 22q13.2 also contributed to PCa susceptibility in different ethnic groups.

CONCLUSIONPCa susceptibility is obviously associated with the risk loci rs1465618, rs721048, rs12621278, rs7679673, rs12653946, rs339331, rs1512268, rs10086908, rs16901979, rs1447295, rs10993994, rs10896449, rs902774, rs9600079, rs11649743 and rs5759167 in Chinese Han population.

Aged ; Asian Continental Ancestry Group ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms ; epidemiology ; genetics ; Risk Factors

OBJECTIVETo investigate the association of the IL-6 -572C > G polymorphism with the risk of prostate cancer (PCa) in the Chinese Han population in Jiangsu and Anhui area.

METHODSWe obtained peripheral blood genome DNA from 200 PCa patients and 279 age-matched PCa-free healthy controls, analyzed the site polymorphism of IL-6 -572C > G with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and studied the correlation of different genotypes with the susceptibility to PCa.

RESULTSThe subjects that carried the CCGG genotype had a risk of PCa 2.46 times that of the CC genotype carriers (95% CI = 1.41-4.29), and 2.47 times that of the CC/GC genotype carriers (95% CI = 1.47-4.17). This risk was significantly increased among the following subgroups of CCGG genotype carriers: age > 70 yr (OR = 3.06, 95% CI: 1.44-6.49), BMI > 23 kg/m2 (OR = 3.72, 95% CI: 1.79-7.74), no cigarette smoking (OR = 2.96, 95% CI: 1.30-6.72), alcohol drinking (OR = 2.73, 95% CI: 1.28-5.79), with a family history of cancer (OR = 6.67, 95% CI: 1.50-29.69).

CONCLUSIONIn the Chinese Han population in Jiangsu and Anhui area, IL-6 -572C > G polymorphism is associated with the susceptibility to PCa, and GG might be a susceptible genotype to PCa.

Aged ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; epidemiology ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-6 ; genetics ; Male ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms ; epidemiology ; genetics

AIMTo assess the role of several genetic factors in combination with an environmental factor as modulators of prostate cancer risk. We focus on allele variants of low-penetrance genes associated with cell control, the detoxification processes and smoking.

METHODSIn a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their prostate cancer risk.

RESULTSThe joint risk for smokers carrying Pro* and M1*, Pro* and GSTM1null or GSTM1 null and CYP1A1 M1* variants was significantly higher (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36; OR: 3.97, 95% CI: 1.13-13.95 and OR: 6.87, 95% CI: 1.68-27.97, respectively) compared with that for the reference group, and for non-smokers was not significant. OR for combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and significantly associated with prostate cancer risk compared with non-smokers and compared with the putative lowest risk group (OR: 8.87, 95% CI: 1.25-62.71).

CONCLUSIONOur results suggest that a combination of p53cd72, CYP1A1, GSTM1 alleles and smoking plays a significant role in modified prostate cancer risk on the study population, which means that smokers carrying susceptible genotypes might have a significantly higher risk than those carrying non-susceptible genotypes.

Aged ; Confidence Intervals ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Amplification ; Genes, p53 ; Genetic Variation ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prostatic Neoplasms ; epidemiology ; genetics ; Risk Factors ; Smoking

Real time quantitative PCR (qPCR) is the method of choice for miRNA expression studies. For relative quantification of miRNAs, normalization to proper reference genes is mandatory. Currently, no validated reference genes for miRNA qPCR in prostate cancer are available. In this study, the expression of four putative reference genes (hsa-miR-16, hsa-miR-130b, RNU6-2, SNORD7) was examined with regard to their use as normalizer. After SNORD7 was already shown an inappropriate reference gene in preliminary experiments using total RNA pools, we studied the expression of the putative reference genes in tissue and normal adjacent tissue sample pairs from 76 men with untreated prostate carcinoma collected after radical prostatectomy. hsa-miR-130b and RNU6-2 showed no significantly different expression between the matched malignant and non-malignant tissue samples, whereas hsa-miR-16 was significantly underexpressed in malignant tissue. Softwares geNorm and Normfinder predicted hsa-miR-130b and the geometric mean of hsa-miR-130b and RNU6-2 as the most stable reference genes. Normalization of the four miRNAs hsa-miR-96, hsa-miR-125b, hsa-miR-205, and hsa-miR-375, which were previously shown to be regulated, shows that normalization to hsa-mir-16 can lead to biased results. We recommend using hsa-miR-130b or the geometric mean of hsa-miR-130b and small RNA RNU6-2 for normalization in miRNA expression studies of prostate cancer.
Aged ; Bias (Epidemiology) ; Carcinoma/diagnosis/*genetics/pathology ; Diagnostic Errors/prevention & control ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/genetics/*metabolism ; Middle Aged ; Polymerase Chain Reaction ; Prostatic Neoplasms/diagnosis/*genetics/pathology ; *Reference Standards