Li-Feng Zhang

Impact of Two Common Xeroderma Pigmentosum Group D (XPD) Gene Polymorphisms on Risk of Prostate Cancer

Background DNA repair genes (eg: xeroderma pigmentosum group D, XPD) may affect the capacity of encoded DNA repair enzymes to effectively remove DNA adducts or lesions, which may result in enhanced cancer risk. The association between XPD gene polymorphisms and the susceptibility of prostate cancer (PCa) was inconsistent in previous studies. Methodology/Principal Findings A meta-analysis based on 9 independent case-control studies involving 3165 PCa patients and 3539 healthy controls for XPD Gln751Lys SNP (single nucleotide polymorphism) and 2555 cases and 3182 controls for Asn312Asp SNP was performed to address this association. Meanwhile, odds ratio (OR) and 95% confidence intervals (CIs) were used to evaluate this relationship. Statistical analysis was performed with STATA10.0. No significant association was found between XPD Gln751Lys SNP and PCa risk. On the other hand, in subgroup analysis based on ethnicity, associations were observed in Asian (eg. Asn vs. Asp: OR = 1.34, 95%CI = 1.16–1.55; Asn/Asn+Asn/Asp vs. Asp/Asp: OR = 1.23, 95%CI = 1.07–1.42) and African (eg. Asn vs. Asp: OR = 1.31, 95%CI = 1.01–1.70; Asn/Asn vs. Asp/Asp: OR = 1.71, 95%CI = 1.03–7.10) populations for Asn312Asp SNP. Moreover, similar associations were detected in hospital-based controls studies; the frequency of Asn/Asn genotype in early stage of PCa men was poorly higher than those in advanced stage of PCa men (OR = 1.45, 95%CI = 1.00–2.11). Conclusion/Significance Our investigations demonstrate that XPD Asn312Asp SNP not the Gln751Lys SNP, might poorly increase PCa risk in Asians and Africans, moreover, this SNPs may associate with the tumor stage of PCa. Further studies based on larger sample size and gene-environment interactions should be conducted to determine the role of XPD gene polymorphisms in PCa risk.

Differential expression of the Wnt/β-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/β-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 β-catenin, Phospho-GSK-3β, and up-regulation of GSK-3β (glycogen synthase kinase-3β), NFκB in fetal male rats was observed by western blot analysis. β-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of β-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/β-catenin pathway in fetal male rats.

Association between IL13 gene polymorphisms and susceptibility to cancer: A meta-analysis

BACKGROUND/AIMS Interleukin-13 (IL13) is an immunoregulatory cytokine which plays an important role in carcinogenesis through affecting tumor immunosurveillance. Many studies had reported the influence of IL13 rs1800925 and rs20541 polymorphisms on cancer risk, however, with inconclusive results. The aim of the present study was to conduct a meta-analysis to clarify the relationship. METHODS Twenty studies including a total of 6713 cancer cases and 8693 controls for IL13 rs20541 polymorphism and 4081 cancer cases and 6202 controls for IL13 rs1800925 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95% confidence intervals were computed to estimate the strength of the association. RESULTS Overall, the IL13 rs20541 polymorphism were associated with significantly decreased cancer risk in all genetic models (AA vs. GG: OR=0.82, 95%CI=0.71-0.95; GA vs. GG: OR=0.92, 95%CI=0.85-0.99; GA/AA vs. GG: OR=0.90, 95%CI=0.85-0.97; AA vs. GG/GA: OR=0.85, 95CI%=0.74-0.98). In the stratified analyses, significant effects were found among European populations, studies with population-based controls and studies of glioma. No influence of the IL13 rs1800925 polymorphism on the overall cancer risk was observed. However, in the stratified analyses, we found the IL13 rs1800925 polymorphism was significantly associated with decreased risk for glioma (CT vs. TT: OR=0.72, 95%CI=0.55-0.93; CT/TT vs. TT: OR=0.76, 95%CI=0.62-0.89). CONCLUSION Our meta-analysis suggests that the IL13 rs20541 polymorphism contributes to susceptibility to cancer, especially for glioma; and the IL13 rs1800925 polymorphism may be associated with glioma risk.

Association between p53 Pro72Arg polymorphism and prostate cancer risk: a meta-analysis.

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios (RR) with 95% confidence intervals (CIs) were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found (Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, Pheterogeneity = 0.016, I2 = 55.8%; Pro/Pro+Pro/Arg vs Arg/Arg, RR = 1.05, 95%CI=1.00-1.11, Pheterogeneity = 0.077, I2 = 51.1%). In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model (RR = 0.31, 95%CI=0.10-0.91, Pheterogeneity = 0.110, I2 =60.8%). This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

Association of a common genetic variant in prostate stem cell antigen with cancer risk.

Introduction Polymorphisms in the prostate stem cell antigen (PSCA) gene have been hypothesized to increase the genetic susceptibility to cancers. The common sequence variation in PSCA rs2294008 (C>T) has been implicated in cancer risk. However, results of the relevant published studies were somewhat underpowered and controversial in general. Material and methods To evaluate the role of PSCA rs2294008 (C>T) genotype in global cancer, we performed a pooled analysis of all the available published studies involving 22,817 cancer patients and 27,753 control subjects. Results The results showed evidence that PSCA rs2294008 (C>T) was associated with increased total cancer risk in the overall comparisons. Stratified analysis by cancer type indicated that PSCA rs2294008 T is associated with increased risk of gastric cancer (OR = 1.24, 95% CI = 1.09–1.42, pheterogeneity < 0.001, I2 = 88.0%) and bladder cancer (OR = 1.07, 95% CI = 1.04–1.11, pheterogeneity = 0.108, I2 = 55.0%) by allelic contrast. Furthermore, in stratified analysis by histological types of gastric cancer, this PSCA variant showed significant associations with diffuse type (OR = 1.81, 95% CI = 1.16–2.81, pheterogeneity < 0.001, I2 = 88.9%) but not intestinal type (OR = 1.29, 95% CI = 0.95–1.74, pheterogeneity < 0.001, I2 = 85.2%) in a dominant genetic model. Similar results were found in Asian and European descendents and population-based studies. Conclusions In all, our meta-analysis suggests that PSCA rs2294008 (C>T) may play allele-specific roles in cancer development. Further prospective studies with larger numbers of participants worldwide should be performed in different kinds of cancer and other descendents in more detail.

Arg462Gln and Asp541Glu polymorphisms in ribonuclease L and prostate cancer risk: a meta-analysis

Objective The association between ribonuclease L (RNASEL) gene polymorphisms and prostate cancer risk has been widely reported, but the results of these studies remained controversial and underpowered. We performed a meta-analysis of 28 studies to evaluate the association between Arg462Gln and Asp541Glu polymorphisms in the RNASEL gene and prostate cancer risk. Methods Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between RNASEL polymorphisms and prostate cancer risk. Results A significantly increased prostate cancer risk was found for the Arg462Gln polymorphism in Africans (Gln/Gln vs Arg/Arg: OR = 2.50, 95%CI = 1.28-4.87; Gln/Gln vs Gln/Arg + Arg/Arg: OR = 2.54, 95%CI = 1.30-4.95), but not in Europeans and Asians. Additionally, the Asp541Glu polymorphism was associated with increased total prostate cancer risk (Glu-allele vs Asp-allele: OR = 1.04, 95%CI = 1.01-1.07; Glu/Glu vs Asp/Asp: OR = 1.22, 95%CI = 1.03-1.46; Glu/Glu vs Glu/Asp + Asp/Asp: OR = 1.09, 95%CI = 1.02-1.16). In the stratified analysis for the Asp541Glu polymorphism, there was a significantly increased prostate cancer risk in Africans and Europeans, and in hospital-based prostate cancer cases. Conclusion The meta-analysis results showed evidence that RNASEL Arg462Gln and Asp541Glu polymorphisms are associated with prostate cancer risk and could be low-penetrance prostate cancer susceptibility biomarkers.

MSMB gene rs10993994 polymorphism increases the risk of prostate cancer

Genome-wide association studies (GWASs) identified microseminoprotein-β (MSMB) gene rs10993994 polymorphism was significantly associated with prostate cancer (PC) risk. However, the association between MSMB gene rs10993994 polymorphism and PC risk remains controversial. Therefore, we performed a systematic review and meta-analysis by searching in the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. A total of 11 publications containing 13 case-control studies for rs10993994 polymorphism were included in our analysis. Our data indicated that MSMB gene rs10993994 polymorphism was associated with an increased risk of PC. Stratification analyses of ethnicity suggested rs10993994 polymorphism increased the risk of PC among Caucasians, but not among Asians. In conclusion, this meta-analysis indicates that MSMB gene rs10993994 polymorphism increases the risk of PC.

Updated analysis of vitamin D receptor gene FokI polymorphism and prostate cancer susceptibility

Introduction Polymorphisms of the vitamin D receptor (VDR) gene have been investigated in various case-control studies to evaluate prostate cancer susceptibility; however, published data on the association between vitamin D receptor gene FokI polymorphism and prostate cancer risk are inconclusive. Material and methods To assess the impact of vitamin D receptor gene FokI polymorphism, we performed a meta-analysis of eligible studies including 9,720 patients and 9,710 control subjects. Results The overall results indicated no obvious association of this variant on prostate cancer risk. However, in subgroup analysis by ethnicity, positive associations existed in Caucasian descendents for allelic contrast (OR = 1.03, 95% CI: 1.00–1.06, pheterogeneity = 0.552, p = 0.026) and the dominant genetic model (OR = 1.03, 95% CI: 1.00–1.05, pheterogeneity = 0.856, p = 0.032). In the subgroup analysis by tumor stage, there was a significant association between this variant and advanced prostate cancer under the recessive genetic model (OR = 1.15, 95% CI: 1.01–1.32, pheterogeneity = 0.469, p = 0.032). In the subgroup analysis by source of control, association of the VDR FokI polymorphism and prostate cancer susceptibility was also found in population-based studies under homozygote comparison and the recessive genetic model. Conclusions The VDR FokI polymorphism may contribute to the risk of developing prostate cancer in Caucasian and population-based studies. Further large, well-designed studies are warranted to confirm this conclusion in more detail.

The Association Between Three Genetic Variants in MicroRNAs (Rs11614913, Rs2910164, Rs3746444) and Prostate Cancer Risk

Background/Aims: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules which play a significant role in transcriptional and translational regulation. Published data on the association between the miRNA SNPs and prostate cancer (PCa) risk are somewhat inconclusive. Methods: We performed a meta-analysis of all available studies including 2,227 patients and 2,331 control subjects to evaluate the impact of three common genetic variants of microRNAs in prostate cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the strength of the association. Results: For miR-499 polymorphism, a significant association was observed between the rs3746444 A>G polymorphism and PCa risk in heterozygote comparison and dominant genetic model, in particular in Asian population subgroup. For miR-146a polymorphism, the rs2910164 CC genotype was associated with decreased PCa risk in Asian population in homozygote comparison. In addition, rs2910164 CC genotype had a weekly higher percentage value in subgroup of Gleason score < 7. Similar results were also indicated in localized prostate cancer in subgroup analysis by tumor stage. For miR-196a2 polymorphism, no association was observed between this variant and PCa risk in the overall group. However, in stratified analysis by ethnicity, we found that rs11614913 T allele was a risk factor for Asian PCa patients. Conclusions: Polymorphisms of miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 may contribute to the risk for developing prostate cancer in Asian descendants. Moreover, miR-146a rs2910164 polymorphism was related to PCa prognosis.

Human methionine synthase A2756G polymorphism increases susceptibility to prostate cancer

Background/Aims: Previous results on the association between MTR gene A2756G polymorphism and PCa risk are inconclusive. Methods: We used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to evaluate the correlation between MTR A2756G polymorphism and risk of PCa in meta-analysis. Serum expression of MTR was detected by ELISA and in-silico tools were utilized to assess this variant. Results: Our study included 2,921 PCa patients and 3,095 control subjects. The results indicated that the MTR A2756G polymorphism is linked with an increased risk of PCa using three genetic models (G-allele vs. A-allele: OR = 1.16, 95%CI = 1.04 - 1.30; GA vs. AA: OR = 1.17, 95%CI = 1.02 - 1.33; GG+GA vs. AA: OR = 1.18, 95%CI = 1.04 - 1.34). Stratified analysis produced similar results. A significant association was also indicated in advanced PCa from the meta-analysis. Finally, our experiments showed evidence that serum MTR levels in PCa patients with AA genotypes were statistically higher than in those with GG/GA genotypes. Conclusions: Our present study suggests that the MTR A2756G polymorphism may contribute to the risk of developing PCa, particularly in Asian and hospital-based studies. Moreover, serum MTR might be utilized in diagnosis of PCa.