SETD4 inhibits prostate cancer development by promoting H3K27me3-mediated NUPR1 transcriptional repression and cell cycle arrest.

The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling.

BACKGROUND: Circular RNAs (circRNAs) mediate the infiltration of tumor-associated macrophages (TAMs) to facilitate carcinogenesis and development of various types of cancers. However, the role of circRNAs in regulating macrophages in prostate cancer (PCa) remains uncertain. METHODS: Differentially expressed circRNAs in PCa were identified by RNA sequencing. The expression of circSMARCC1 was recognized and evaluated using fluorescence in situ hybridization and quantitative real-time PCR. The oncogenic role of circSMARCC1 in PCa tumor proliferation and metastasis was investigated through a series of in vitro and in vivo assays. Finally, Western blot, biotin-labeled RNA pulldown, luciferase assay, rescue experiments, and co-culture experiments with TAMs were conducted to reveal the mechanistic role of circSMARCC1. RESULTS: CircSMARCC1 was dramatically up-regulated in PCa cells, plasma and tissues. Overexpression of circSMARCC1 promotes tumor proliferation and metastasis both in vitro and in vivo, whereas knockdown of circSMARCC1 exerts the opposite effects. Mechanistically, circSMARCC1 regulates the expression of CC-chemokine ligand 20 (CCL20) via sponging miR-1322 and activate PI3K-Akt signaling pathway involved in the proliferation and epithelial mesenchymal transformation. More importantly, high expression of circSMARCC1 was positively associated with colonization of CD68+/CD163+/CD206+ TAMs in tumor microenvironment. In addition, overexpression of circSMARCC1 facilitates the expression of CD163 in macrophages through the CCL20-CCR6 axis, induces TAMs infiltration and M2 polarization, thereby leading to PCa progression. CONCLUSIONS: CircSMARCC1 up-regulates the chemokine CCL20 secretion by sponging miR-1322, which is involved in the crosstalk between tumor cells and TAMs by targeting CCL20/CCR6 signaling to promote progression of PCa.

BAP1-Related ceRNA (NEAT1/miR-10a-5p/SERPINE1) Promotes Proliferation and Migration of Kidney Cancer Cells.

Background: BAP1 is an important tumor suppressor involved in various biological processes and is commonly lost or inactivated in clear-cell renal cell carcinoma (ccRCC). However, the role of the BAP1-deficient tumor competing endogenous RNA (ceRNA) network involved in ccRCC remains unclear. Thus, this study aims to investigate the prognostic BAP1-related ceRNA in ccRCC. Methods: Raw data was obtained from the TCGA and the differentially expressed genes were screened to establish a BAP1-related ceRNA network. Subsequently, the role of the ceRNA axis was validated using phenotypic experiments. Dual-luciferase reporter assays and fluorescence in situ hybridization (FISH) assays were used to confirm the ceRNA network. Results: Nuclear enriched abundant transcript 1 (NEAT1) expression was significantly increased in kidney cancer cell lines. NEAT1 knockdown significantly inhibited cell proliferation and migration, which could be reversed by miR-10a-5p inhibitor. Dual-luciferase reporter assay confirmed miR-10a-5p as a common target of NEAT1 and Serine protease inhibitor family E member 1 (SERPINE1). FISH assays revealed the co-localization of NEAT1 and miR-10a-5p in the cytoplasm. Additionally, the methylation level of SERPINE1 in ccRCC was significantly lower than that in normal tissues. Furthermore, SERPINE1 expression was positively correlated with multiple immune cell infiltration levels. Conclusions: In BAP1-deficient ccRCC, NEAT1 competitively binds to miR-10a-5p, indirectly upregulating SERPINE1 expression to promote kidney cancer cell proliferation. Furthermore, NEAT1/miR-10a-5p/SERPINE1 were found to be independent prognostic factors of ccRCC.

Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p.

BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

[A simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves immediate continence].

OBJECTIVE: To investigate the application of a simplified technique for reconstruction of vesicourethral support (RVUS) in laparoscopic radical prostatectomy (LRP). METHODS: From January 2017 to August 2019, 122 patients with localized prostate cancer underwent extraperitoneal LRP, 65 with RVUS (the RVUS group) and 57 without RVUS (the non-RVUS group). We compared the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, incidence of urethrovesical anastomotic urinary leakage (UVAUL), postoperative urinary continence, postoperative hospital stay, intraperitoneal drainage tube removal time, and urethral catheter removal time between the two groups of patients. RESULTS: No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, or urethral catheter removal time (P > 0.05). The incidence rate of UVAUL was lower in the non-RVUS than in the RVUS group (8.8% vs 0%, P < 0.05), and so were the rates of postoperative urinary continence immediate after (0% vs 32.3%, P < 0.05) and at 1 month (38.6% vs 56.9%, P < 0.05), 3 months (59.6% vs 80%, P < 0.05), 6 months (78.9% vs 84.6%, P > 0.05) and 12 months after catheter removal (87.7% vs 92.3%, P > 0.05). The postoperative hospital stay was dramatically longer in the non-RVUS than in the RVUS group (ï¼»9.1 ± 4.3ï¼½ vs ï¼»6.7 ± 1.8ï¼½ d, P < 0.01) and so was the intraperitoneal drainage tube removal time (ï¼»6.9 ± 4.5ï¼½ vs ï¼»4.8 ± 1.5ï¼½ d, P < 0.01). CONCLUSIONS: The simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves early urinary continence, especially immediate continence, decreases the incidence rate of urethrovesical anastomotic urinary leakage, and shortens the intraperitoneal drainage tube removal time and postoperative hospital stay.?

[Hydrogen-rich water improves progressive sperm motility in rats by reducing oxidative stress and upregulating CLDN3 and SRD5A2 expressions].

Objective: To investigate the protective effect of long-term consumption of hydrogen-rich water (HRW) on the percentage of progressively motile sperm (PMS) in male rats. METHODS: Twenty normal healthy male SD rats were equally randomized into an HRW and a control group, the former given HRW (1.2 ppm) and the latter normal saline, both intragastrically at 2 ml/d for 9 months. Then, the bilateral epididymides of the rats were harvested for preparation of sperm suspension and detection of the percentage of PMS. The testis tissue was isolated for HE staining and determination of the expressions of the Ki67, CYBB, eNOS, CLDN3 and SRD5A2 proteins using the streptavidin-peroxidase (SP) immunohistochemical method. RESULTS: The percentage of PMS was significantly higher in the HRW than in the control group (ï¼»64.3 ± 4.7ï¼½% vs ï¼»55.3 ± 9.5ï¼½%, P < 0.05), and so was the expression of Ki67 in the testicular tissue (P < 0.01). Compared with the controls, the rats in the HRW group showed markedly decreased oxidative stress-related index CYBB (P < 0.01), increased eNOS level (P < 0.01), and upregulated expressions of sperm development-related proteins CLDN3 and SRD5A2 (P < 0.01 and P < 0.05). CONCLUSIONS: Hydrogen not only regulates the expressions of some oxidative stress-related indicators, but also increases the expressions of the molecules promoting sperm maturation and motility, which provides a theoretical basis and experimental support for the application and studies of hydrogen in asthenospermia.

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth.

The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.

Immunotherapy and endothelin receptor antagonists for treatment of castration-resistant prostate cancer.

Recently, novel therapies of prostate cancer, such as immunotherapy, endothelin receptor antagonists, novel androgen receptor antagonist and novel taxanes, and others have been introduced into clinical practice. This study was performed to summarize these results of immunotherapy and endothelin receptor antagonists in the treatment of castration-resistant prostate cancer (CRPC) and derive a more precise estimation of their effect on future treatment. The PubMed database, references of published trials, and review articles were searched. Two reviewers independently extracted data of these trials. We used hazard ratios (HRs) to assess the effects on overall survival (OS), progression-free survival (PFS), or time to disease progression (TTP), and relative risk (RR) for the different types of toxicity. In addition, 95% confidence intervals (CIs) give a sense of the precision of the estimate. Nine randomized controlled trials were ultimately identified. The pooled HR showed that immunotherapy could prolong OS significantly in patients with CRPC compared to placebo (HR = 0.70, 95% CI: 0.58-0.83, p < 0.001). Endothelin receptor antagonists also had modest benefits (HR = 0.90, 95% CI: 0.82-1.00, p = 0.046). Nevertheless, there were no significant benefits from both therapies on PFS or TTP. In addition, immunotherapy led to more fatigue, pyrexia, chills, and endothelin receptor antagonists led to more peripheral edema, anemia, and dyspnea. Our article suggested that the very acceptable toxicity and improving OS in patients with CRPC made immunotherapy an attractive option for such patients. However, future studies with thoughtful clinical trial designs are warranted.

A modified method for the treatment of urethral fistula after hypospadias repair.

Urethrocutaneous fistula (UCF) is a common complication of hypospadias surgery for severe hypospadias. We report our experience in the management of UCF following hypospadias surgery with a prepuce-degloving method (PDM). Our study included 87 patients who developed UCF after hypospadias repair from May 2001 to December 2011. Either simple closure or PDM was performed to repair the fistula. In total, 61 patients underwent a simple closure or Y-V plasty of the fistula, and 26 underwent a PDM repair. The success rate was 78.7% for simple closure or Y-V plasty and 96.2% for PDM repair (P<0.05). PDM repair represents a good choice for UCF repair after hypospadias, and our high 96.2% success rate demonstrates its applicability.

Role of the functional MKK4 promoter variant (-1304T>G) in a decreased risk of prostate cancer: case-control study and meta-analysis.

PURPOSE: MKK4 has been suggested as a tumor suppressor. The functional variant (-1304T>G) in the MKK4 promoter has been implicated as a risk factor for many types of cancer. However, its role in prostate cancer (PCa) is unclear. To determine whether this SNP constitutes a risk factor for PCa susceptibility and to derive a more precise estimation of the associations between this SNP and cancer risk, we performed a case-control study and then a meta-analysis covering previous case-control studies. METHODS: In this study, 222 male patients with PCa and 244 cancer-free controls were evaluated MKK4-1304T>G genotype. The transcriptional activity of MKK4 gene was measured by luciferase assay, and MKK4 serum expression was measured by ELISA. RESULTS: As a whole, we found that compared to the most common -1304TT genotype, carriers of -1304G variant genotypes had a decreased risk of PCa (OR = 0.670; 95 % CI = 0.452-0.993, P = 0.046 for TG, and OR = 0.647; 95 % CI = 0.441-0.948, P = 0.025 for TG + GG). We found that carriers of the -1304G variant genotypes had greater transcriptional activity and serum expression of MKK4 than carriers of the -1304T allele. Our meta-analysis also suggested that the -1304G variant contributes to decreased risk of various cancers. CONCLUSION: Our results suggest that the functional -1304G variant in the MKK4 promoter decreases the risk of PCa by increasing the promoter activity. In the future, prospective researches on patients from many parts of the world may validate our findings.

An updated meta-analysis of XRCC4 polymorphisms and cancer risk based on 31 case-control studies.

OBJECTIVE: Evidence is accumulating that several genes encoding DNA repair molecules may be cancer-susceptibility genes. Recently, SNPs in XRCC4, a member of DNA repair genes, have been implicated in altering the risk of various cancers. However, the results of these studies are inconclusive or controversial. To derive a more precise estimation, we performed an updated meta-analysis. METHODS: A comprehensive search was conducted to examine all the eligible studies about XRCC4 polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. RESULTS: We included 31 studies investigated 8 SNPs in XRCC4. Overall, our paper showed significant associations between the rs28360071, rs2075686 polymorphisms and cancer risk. In addition, significant association was maintained in prostate cancer (rs28360071), lung cancer (rs6869366) and bladder cancer (rs1805377) subgroups analysis. CONCLUSIONS: We conducted a systematic search and combined the available results in this meta-analysis, which provided evidence of the associations between SNPs in XRCC4 and cancer risk. The results suggested that rs28360071 polymorphisms were significantly associated with cancer risk. However, future studies are needed to investigate molecular mechanisms underlying the biological functions of XRCC4 SNPs in cancer development.

Differential expression of the Wnt/ß-catenin pathway in the genital tubercle (GT) of fetal male rat following maternal exposure to di-n-butyl phthalate (DBP).

Di-n-butyl phthalate (DBP) is one of the most abundantly produced endocrine disruptors that leaches out from polyvinyl chloride plastics and can cause hypospadias in male rats during maternal exposure. The objective of this study was to first explore the roles of Wnt/ß-catenin pathway in the fetal rat genital tubercle (GT) following in-utero exposure to DBP. Timed-pregnant rats were given DBP by gastric intubation at a dose of 750 mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a rat model of hypospadias. On GD19, genital tubercle down-regulation of ß-catenin, Phospho-GSK-3ß, and up-regulation of GSK-3ß (glycogen synthase kinase-3ß), NFκB in fetal male rats was observed by western blot analysis. ß-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of ß-catenin decreased in the DBP-treated fetal rat GT compared to the normal control. These findings, for the first time, indicate that DBP may affect the development of GT by down-regulating the Wnt/ß-catenin pathway in fetal male rats.

[TRAIL gene polymorphism and genetic susceptibility to prostate cancer in the Chinese Han population of Nanjing].

OBJECTIVE: To investigate the correlation between the polymorphism of the tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and the genetic susceptibility to prostate cancer (PCa) in the Chinese Han population in Nanjing. METHODS: We performed a case control study on 187 cases of PCa and 237 cancer-free healthy controls. Peripheral blood genome DNA was extracted from the subjects for analysis of the polymorphism of the TRAIL-716 locus by polymerase chain reaction-ligase detection reaction (PCR-LDR). The correlations between the susceptibility to PCa and different genotypes were compared. RESULTS: An SNP (-716A/G) was found in the promoter of the TRAIL gene. AA, AG and GG genotypes were identified. Logistic regression analysis suggested that AG, GG and AG + GG genotypes had no significant correlation with the risk of PCa (OR = 0.89, 95% CI = 0.54 -1.47; OR = 0.94, 95% CI = 0.69 -1.27; OR = 0.87, 95% CI = 0.54 - 1.41). CONCLUSION: The TRAIL-716 polymorphism is not directly related with the genetic susceptibility to PCa in the Chinese Han population of Nanjing.

An update analysis of two polymorphisms in encoding ribonuclease L gene and prostate cancer risk: involving 13,372 cases and 11,953 controls.

Encoding ribonuclease L (RNASEL) is a ubiquitously expressed latent endoribonuclease involved in the mediation of antiviral and pro-apoptotic activities of the interferon-inducible 2-5A system. Although the relationship between RNASEL gene polymorphisms and prostate cancer (PCa) risk has been widely reported, results were somewhat controversial and underpowered. Now, we performed an update analysis of 14 publications evaluating the association between RNASEL R462Q and D541E polymorphisms and PCa risk. We conducted a literature search of PubMed database to identify all eligible articles that examined the association of RNASEL R462Q and D541E polymorphisms with PCa. Odds ratios (OR) with 95% confidence intervals (CI) were estimated to assess these association. R462Q showed a significantly elevated effect on Africans (QQ vs. RR: OR = 2.50, 95% CI = 1.28-4.87, P (heterogeneity) = 0.231). In addition, PCa men who contain 462Q genotype had a higher Gleason score ≥ 7 (OR = 1.16, 95% CI = 1.05-1.28, P (heterogeneity) = 0.906). On the other hand, D541E was associated with increased total PCa. In the stratified analysis by race, there was also significantly increased PCa in Africans and Caucasians, as well as in sporadic PCa studies (OR = 1.09, 95% CI = 1.04-1.15, P (heterogeneity) = 0.078). Our update analysis showed evidence that RNASEL R462Q and D541E polymorphisms were associated with PCa risk. Still more well-designed studies should be performed to clarify the role of these two polymorphisms in the development of PCa.

RNASEL -1385G/A polymorphism and cancer risk: a meta-analysis based on 21 case-control studies.

Polymorphisms in the endoribonuclease L (RNASEL) gene have been hypothesized to increase the incidence of cancer. The common sequence variation in RNASEL, -1385G/A (rs486907) has been involved in several types of cancer risk. However, results of the related published studies remained conflicting rather than conclusive. To clarify the role of RNASEL -1385G/A genotype in global cancer, we performed a meta-analysis of all the available published studies involving 8,732 cancer patients and 8,748 control subjects. The overall results indicated that there was no major influence of the variant on cancer risk. However, stratified analysis by ethnicity showed that the RNASEL -1385G/A polymorphism has an increased cancer risk in African descendents in the homozygote comparison (OR = 2.59, 95% CI = 1.27-5.27), although no association was found in the analysis stratified by cancer type (OR = 1.12, 95% CI = 0.94-1.35). This meta-analysis suggested that the RNASEL -1385G/A polymorphism is associated with cancer risk in African descendents. To draw more comprehensive conclusions, further prospective studies with larger numbers of participants worldwide are still required to examine associations between RNASEL -1385G/A polymorphism and cancer risk.

Interferon gamma +874 T/A polymorphism contributes to cancer susceptibility: a meta-analysis based on 17 case-control studies.

Interferon gamma (IFN-γ) plays a pivotal role in antiproliferative, antitumor and antiviral activities. The +874 polymorphism in IFN gene region reportedly affects cancer risk. However, pertinent studies offer conflicting results. To derive a more precise estimation, we performed a meta-analysis based on 1,929 cases and 2,830 controls from 17 published case-control studies, assessing the strength of the association using odds ratios with 95% confidence intervals. Our meta-analysis showed the evidence that IFN-γ +874 T/A was not associated with increased cancer risk in ethnicity and source of controls. However, stratified analysis by cancer type indicated a significantly increased risk of cervical cancer (AT vs. TT: OR = 1.10, 95% CI = 1.02-1.19, P = 0.961 for heterogeneity). Further prospective researches with a larger single study are required to evaluate any association with other types of cancer or in other populations.

IL-6 -174G>C polymorphism and cancer risk: a meta-analysis involving 29,377 cases and 37,739 controls.

Interleukin-6 (IL-6) is a multifunctional cytokine involved in different physiologic and pathophysiologic processes and plays important roles in the etiology of cancer. The -174G>C polymorphism of the IL-6 gene influences IL-6 transcription and has been implicated in cancer risk. However, published data have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 29,377 cancer cases and 37,739 controls from 50 published case-control studies was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between -174G>C polymorphism and cancer risk. Overall meta-analysis indicated that no association was found between -174G>C genotypes and cancer risk. However, the positive association was found in bladder cancer (OR=4.33, 95% CI: 1.93-9.71 for CC vs. GC, OR=2.81, 95% CI: 1.39-5.68 for CC vs. GG, and OR=2.19, 95% CI: 1.32-3.64 for CC vs. GG/GC), and among Asians (OR=2.08, 95% CI: 1.07-4.06 for CC vs. GG, and OR=2.20, 95% CI: 1.02-4.74 for CC vs. GG/GC) and Africans (OR=1.61, 95% CI: 1.07-2.42 for GC vs. GG). This meta-analysis showed the evidence that the -174G>C of the IL-6 gene was a low-penetrance susceptibility gene for bladder cancer. Further larger, preferably prospective studies are needed to confirm this relationship.

Review and pooled analysis of studies on -607(C/A) and -137(G/C) polymorphisms in IL-18 and cancer risk.

Interleukin-18 (IL-18) is a pleiotropic, pro-inflammatory cytokine with dual effects on tumor development and progression. The -607(C/A) and -137(G/C) polymorphisms in IL-18 gene region have been implicated in cancer risk; however, data from published studies with individually low statistical power are conflicting. To clarify the role of IL-18 -607(C/A) and -137(G/C) genotype in global cancer, we examined all the available published studies through a pooled analysis approach. Overall, IL-18 -607A allele was associated with increased total cancer risk when compared with -607C allele (OR=1.14, 95% CI=1.01-1.28, P=0.010), as well as in the heterozygote comparison (OR=1.10, 95% CI=1.04-1.15, P=0.256) and the dominant model (OR=1.07, 95% CI=1.03-1.11, P=0.124). Furthermore, IL-18 -137(G/C) polymorphism was associated with increased nasopharyngeal carcinoma risk. In the stratified analysis for -607(C/A) polymorphism, a significantly increased cancer risk in Asian population was found, as well as subgroup in source of control. Similar results were found in the stratified analysis for -137(G/C) polymorphism. Our pooled analysis supported that IL-18 is a good candidate for large-scale epidemiological case-control studies that may be a low-penetrance susceptibility biomarker for cancer.

Association between polymorphisms of TP53 and MDM2 and prostate cancer risk in southern Chinese.

Alterations in the TP53 and MDM2 genes appear to be important in the development of many human tumors, but evidence is conflicting on associations between polymorphisms in these genes and risk of prostate cancer (PCa). The influence of TP53 codon 72, MDM2 SNP309, and MDM2 C1797G polymorphisms in southern Chinese PCa patients was investigated. In the comparison of genotype distributions of TP53 codon 72 between cases and controls, the adjusted odds ratios for PCa associated with the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 1.00, 1.89 (95% CI = 1.20-2.97), and 2.01 (95% CI = 1.11-3.64), respectively; however, MDM2 SNP309 and C1797G did not show any significant difference between cases and controls. When TP53 and MDM2 polymorphisms were combined based on the numbers of variant risk alleles (i.e., G-allele of TP53 codon 72, G-allele of MDM2 SNP309, and G-allele of MDM2 C1797G), individuals with 3-5 variants had a 1.56-fold greater risk of PCa than those with 0-2 variants (95% CI = 1.07-2.26). Moreover, subjects with 0-2 variants had 33.3% positive p53 expression, whereas subjects with 3-5 variants had 23.3% p53 expression (P = 0.39). These findings suggest that TP53 and MDM2 polymorphisms play a role in PCa susceptibility in southern Chinese Han population.