[Differential expressions of seminal plasma piRNAs in men and its significance].

OBJECTIVE: To study the differential expressions of piRNAs in the seminal plasma of men and the role of piRNAs in spermatogenesis. METHODS: We sequenced the seminal plasma samples collected from 187 male infertility patients and 58 normal healthy men, obtained differentially expressed piRNAs, and detected the relative expressions of piRNAs in different types of sperm by RT-qPCR to explore their significance in the diagnosis of male infertility. Using histopathology, RNA-protein pull-down and Western blot, we investigated the action mechanism of piRNAs in spermatogenesis in the mouse model. RESULTS: RT-qPCR of the seminal plasma samples revealed a high expression of hsa_piR_000478 in teratozoospermia and ROC curve analysis showed an auxiliary significance of hsa_piR_000478 in the diagnosis of the disease (AUC = 0.7549). Transfection of hsa_piR_000478 and its homologous sequence piR_mmu_54800729 into the seminiferous tubules of the mouse model significantly decreased sperm motility, increased the percentage of morphologically abnormal sperm and destroyed the testicular structure. Molecular biological experiments exhibited a close correlation between piRNAs and the energy metabolism-related pathway, which elevated the level of cell glycolysis and interfered with normal spermatogenesis. CONCLUSION: hsa_piR_000478 has an auxiliary significance in the diagnosis of male infertility, and piRNAs may interfere with spermatogenesis by affecting the glycolysis-related pathway in the spermatogenic microenvironment of the testis.

Development and Characterization of a Novel Hydrogel for the Decontaminating of Radionuclide-Contaminated Skin Wounds.

Designing skin decontaminating materials with outstanding therapeutic effects, adhesiveness, and suitable mechanical property has great practical significance in radionuclide-contaminated skin wound healing. Here, a physically crosslinked hydrogel is constructed via hydrogen bonding of poly acrylamide, sodium alginate (SA), and the complexing agent diethylene triamine pentaacetic acid (DTPA). The physical and chemical properties of the poly(AAm-SA-DTPA) hydrogel (PASD) are detected according to established methods. The decontaminating property and skin wound healing of the PASD are investigated to confirm multi-functions of wound dressing. The physical and chemical properties results show that the synthesis of the PASD hydrogel is effective and that DTPA is present in the hydrogel. The hydrogel also shows great mechanical and swelling properties. In vitro tests find that PASD shows significant scavenging abilities for strontium and cerium. In vivo experiments show that the PASD hydrogel can remove radioactive strontium from the skin wounds of mice, and can effectively prevent the absorption of radioactive strontium through the skin wound. Furthermore, the PASD hydrogel can effectively promote the formation of granulation tissue in a radioactive contaminated wound. Taken together, the PASD hydrogels, which has good mechanical properties and radionuclides decontamination, is expected to be used as a dressing for radionuclide-contaminated skin wound healing.

Tritiated Water Induces Toxicity in Human Umbilical Vein Vascular Endothelial Cells via IL8.

We aimed to determine the toxic effects of tritiated water (HTO) on 12 generations (T1-T12) of human umbilical vein vascular endothelial cells (HUVECs) and elucidate the underlying mechanisms. We evaluated cellular senescence, interleukin (IL) 8 concentrations, and angiogenesis using ß-galactosidase staining, enzyme-linked immunosorbent assay, and in vitro assays, respectively. The adhesion properties of contaminated cells and differentially expressed genes were assessed using the xCELLigence RTCA SP system and gene chip analysis, respectively. We found that long-term exposure to low levels of HTO can reduce the adhesion of HUVECs to the cellular matrix as well as their angiogenic capacity, while increasing their permeability, senescence, and adhesion to monocytes. Interleukin 8 activated the p38 and Epidermal Growth Factor Receptor (EGFR) pathways in HTO-treated cells and hence was identified as a key candidate of biomarker. The present study clarified the toxicity of HTO in vascular endothelial cells and identified IL8 as a novel protective target with important theoretical and practical values.

LKB1 inactivation leads to centromere defects and genome instability via p53-dependent upregulation of survivin.

Inactivating mutations in the liver kinase B1 (LKB1) tumor suppressor gene underlie Peutz-Jeghers syndrome (PJS) and occur frequently in various human cancers. We previously showed that LKB1 regulates centrosome duplication via PLK1. Here, we report that LKB1 further helps to maintain genomic stability through negative regulation of survivin, a member of the chromosomal passenger complex (CPC) that mediates CPC targeting to the centromere. We found that loss of LKB1 led to accumulation of misaligned and lagging chromosomes at metaphase and anaphase and increased the appearance of multi- and micro-nucleated cells. Ectopic LKB1 expression reduced these features and improved mitotic fidelity in LKB1-deficient cells. Through pharmacological and genetic manipulations, we showed that LKB1-mediated repression of survivin is independent of AMPK, but requires p53. Consistent with the key influence of LKB1 on survivin expression, immunohistochemical analysis indicated that survivin is highly expressed in intestinal polyps from a PJS patient. Lastly, we reaffirm a potential therapeutic avenue to treat LKB1-mutated tumors by demonstrating the increased sensitivity to survivin inhibitors of LKB1-deficient cells.

Monitoring of Tritium Internal Exposure Doses of Heavy-Water Reactor Workers in Third Qinshan Nuclear Power Plant.

To analyze the tritium internal exposure dose of workers in the Third Qinshan Nuclear Power Plant over the past 15 years. Urine samples provided by workers are tested directly to analyze the tritium concentrations and estimate internal exposure dose. Since 2004, an average of approximately 1600 workers have been monitored annually, with an average annual monitoring frequency of approximately 11 000. Since 2004, the average annual collective dose of tritium internal exposure was 149.62 person·mSv, accounting for 19.07% of the total annual collective dose. A total of 18 workers' annual individual internal tritium radiation doses exceeded 2 mSv, of which 5 workers' internal tritium radiation doses in a single intake exceeded 2 mSv. The occupational population with the largest total internal tritium radiation doses consists of maintenance personnel, fuel operators, and radiation protection personnel, whose collective doses of internal exposure account for 75.51% of the total collective doses within the plant. Over 15 years of operation, the internal tritium radiation doses of workers in the Third Qinshan Nuclear Power Plant have been strictly controlled within the national regulatory limit and power plant management target, ensuring the health and safety of the workers.

Polydatin Increases Radiosensitivity by Inducing Apoptosis of Stem Cells in Colorectal Cancer.

This study aimed to investigate the radiosensitizing effect of polydatin (PD) on colorectal cancer (CRC) and its underlying mechanism. The C57BL/6 mouse model of CRC was induced by treatment with azoxymethane (AOM)/dextran sodium sulfate (DSS) and then divided into four groups: control, PD alone, IR alone, and combination of PD and IR. Radiation therapy (200 cGy/min, 10Gy) was performed in mice in the experimental groups for once a week with a total of four times. Thirty minutes before IR, mice were intraperitoneally injected with PD at the dose of 25mg/kg. The number and volume of CRC xenografts were calculated. Immunohistochemical staining was performed to detect the expression of Ki67 and cleaved caspase-3 in tumor tissues samples. The effects of PD on proliferation and apoptosis were evaluated in CT26 and HCT116 colon tumor cells. Leucine-rich repeat-containing G-protein coupled receptor 5 positive (Lgr5+) cancer stem cells (CSCs) were sorted from CT26 cells and the effects of PD on their proliferation and apoptosis were observed to elucidate the radiosensitizing mechanism of PD in CRC cells. Combined therapy with PD and IR significantly decreased tumor volume, inhibited proliferation and induced apoptosis of tumor cells in the mouse model of CRC compared to other three groups. Compared to the IR group, in vitro assay showed that PD combined with IR inhibited proliferation and promoted apoptosis of CT26 and HCT116 colon tumor cells as well as Lgr5+ CSCs. However, addition of the bone morphogenetic protein (BMP) type I receptor inhibitor K02288 (6.4nM) dramatically increased proliferation of Lgr5+ CSCs and abolished the cytotoxic effect of PD combined with IR on Lgr5+ CSCs. The in vivo and in vitro experiments demonstrated that IR combined treatment with PD could inhibit proliferation and promote apoptosis of CRC cells and Lgr5+ CSCs, and BMP signaling pathway was involved in the radiosensitizing effect of PD.

Protective effect of polydatin on radiation-induced injury of intestinal epithelial and endothelial cells.

This study aimed to examine the radioprotective effect of polydatin (PD) on crypt and endothelial cells of the small intestines of C57BL/6 mice that received abdominal irradiation (IR). Mice were treated with 6 MV X-ray (20 Gy) abdominal IR at a dose rate of 200 cGy/min. Thirty minutes before or after IR, mice were intraperitoneally injected with PD. The rate of survival of the mice at 30 days after IR was determined. The duodenum (upper small intestine), jejunum (middle small intestine), and ileum (lower small intestine) were collected and subjected to hematoxylin and eosin staining. Tissue sample sections were analyzed through light microscopy, and the lengths of at least 20 intestinal villi were measured in each group; the average number of crypts was obtained from 10 intestinal samples in each group. Microvessel density was assessed using CD31-positive (brown) vascular endothelial cells/cell clusters. FHs74Int cell proliferation was measured using the CCK-8 assay. PD administration (25 mg/kg) before IR was the most effective in prolonging the survival of C57BL/6 mice. PD reduced radiation-induced injury of intestinal villi, prevented loss of crypts, increased intestinal crypt growth, protected against IR-induced intestinal injury, and enhanced the proliferative potential and reduced the apoptosis of FHs74Int cells after IR. Moreover, PD increased small intestinal MVD and reduced the apoptosis of intestinal microvascular endothelial cells in mice after IR. Therefore, PD was found to be able to protect the two types of cells from radiation damage and to thus alleviate radiation-induced injury of small intestine.

Establishing age and sex dependent upper reference limits for the plasma lipoprotein (a) in a Chinese health check-up population and according to its relative risk of primary myocardial infarction.

BACKGROUND: Though lipoprotein (a) (Lp (a)) has been considered as a risk factor for coronary artery disease, there is a lack of cutoff values of Lp (a) for Chinese Han ethnicity. METHODS: We included 1 population for health check-ups. Lp (a) percentile distributions were analyzed and its cutoff for Chinese Han ethnicity was also proposed according to the its relative risk of myocardial infarction. RESULTS: Lp (a) distributions differed between sexes, and were highly skewed towards low concentrations with a long tail towards the highest ones. The relative risks of elevated Lp (a) concentrations for myocardial infarction had an inflection in Chinese Han ethnic at the 8th decile, corresponding to 167 mg/l, where the risk was prone to be increased. In terms of Lp (a) median concentrations, per higher age quantile (5-y interval) was associated with a significant increase of 3.2 mg/l and females were on average 19.75 mg/l higher than males with a significant difference. CONCLUSIONS: We proposed Lp (a) < 170 mg/l after rounding as cut-off values for Chinese Han ethnicity. Effects of age and sex on Lp (a) concentrations were also noted. Prospective validation of these cutoff values is critically important in Chinese Han ethnicity.

Exosomal miR-7 Mediates Bystander Autophagy in Lung after Focal Brain Irradiation in Mice.

This study investigated whether exosomal microRNA-7 (miR-7) mediates lung bystander autophagy after focal brain irradiation in mice. After 10 Gy or sham irradiation of mice brains, lung tissues were extracted for the detection of autophagy markers by immunohistochemistry, western blotting, and quantitative real-time reverse transcription PCR (qRT-PCR), meanwhile the brains were dissociated, the neuron/astrocyte/microglia/oligodendrocyte were isolated, and the miR-7 expression in each population were detected, respectively. A dual-luciferase reporter assay was developed to identify whether Bcl-2 is a target gene of miR-7. After 10 Gy or sham irradiation of astrocytes, exosomes were extracted, stained with Dil (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindocarbocyanine Perchlorate), and added into non-irradiated astrocytes. Meanwhile, Dil-stained exosomes released from 10 Gy or sham irradiated astrocytes were injected into LC3B-GFP mice via the tail vein. Lung tissues were then extracted for western blotting and qRT-PCR. Irradiation of mouse brains increased the LC3B-II/I ratio, Beclin-1 and miR-7 levels, while decreased the Bcl-2 level in non-irradiated lung tissue. Interestingly, brain irradiation remarkably increased the miR-7 expression in astrocyte and oligodendrocyte. MiR-7 significantly inhibited the luciferase activity of the wild-type Bcl-2-3'-untranslated regions (UTR) reporter vector, but not that of the Bcl-2-3'-UTR mutant vector, indicating that Bcl-2 is directly targeted by miR-7. In in vitro study, the addition of irradiated astrocyte-secreted exosomes increased the LC3B-II/I ratio, Beclin-1 and miR-7 levels, while decreased the Bcl-2 level in non-irradiated astrocytes. Further, the injection of irradiated astrocyte-secreted exosomes through the tail vein increased the lung LC3B-II/I ratio, Beclin-1 and miR-7 level, but decreased the Bcl-2 level in vivo. We concluded that exosomal miR-7 targets Bcl-2 to mediate distant bystander autophagy in the lungs after brain irradiation.

Inhibition of c-Myc expression accounts for an increase in the number of multinucleated cells in human cervical epithelial cells.

The present study aimed to explore the mechanisms by which c-Myc is involved in mitotic catastrophe. HeLa-630 is a cell line stably silenced for c-Myc expression that was established in the laboratory of the School of Radiation Medicine and Protection. Multinucleated cells were observed in this line, and gene expression analysis was utilized to examine differences in gene expression in these cells compared with in the control cells transfected with the control plasmid. Gene ontology analysis was performed for differentially expressed genes. Expression profile analyses revealed that cells with silenced c-Myc exhibited abnormal expression patterns of genes involved in various functions, including the regulation of microtubule nucleation, centrosome duplication, the formation of pericentriolar material, DNA synthesis and metabolism, protein metabolism and the regulation of ion concentrations. Pathway analyses of differentially expressed genes demonstrated that these genes were primarily involved in diverse signal transduction pathways, including not only the adherens junction pathway, the transforming growth factor-ß signaling pathway and the Wnt signaling pathway, among others, but also signaling pathways with roles in cytokine and immune regulation. The proportion of multinucleated cells with multipolar spindles was significantly higher in silenced c-Myc cells as compared with the control cells, and this discrepancy became more pronounced following cell irradiation. The inhibition of c-Myc in tumors may account for the radiosensitization of certain tumor cell types.

The Role of miR-34a in Tritiated Water Toxicity in Human Umbilical Vein Endothelial Cells.

In this work, we investigated the toxic effects of tritiated water (HTO) on the cardiovascular system. We examined the role of microRNA-34a (miR-34a) in DNA damage and repair in human umbilical vein endothelial cells (HUVECs) exposed to HTO. Cell proliferation capacity was evaluated by cell counting, and miR-34a expression was detected using quantitative PCR (QT-PCR). The Comet assay and γ-H2AX immunostaining were used to measure DNA double-strand breaks (DSBs). Reverse transcription polymerase chain reaction was used to measure the expression level of c-myc messenger RNA (mRNA). The cells exposed to HTO showed significantly lower proliferation than the control cells over 3 days. The DNA damage in the HTO group was more severe than that in the control group, at each time point examined. The expression of miR-34a mimics caused increased DNA DSBs whereas that of the miR-34a inhibitor caused decreased DNA DSBs. The proliferation viability was the opposite for the miR-34a mimics and inhibitor groups. The expression levels of c-myc mRNA in cells transfected with miR-34a mimics were lower than that in cells transfected with the miR-34a-5p inhibitor, at 0.5 hours and 2 hours after transfection. In summary, miR-34a mediates HTO toxicity in HUVECs by downregulating the expression of c-myc.

Management of symptomatic caliceal diverticular calculi: Minimally invasive percutaneous nephrolithotomy versus flexible ureterorenoscopy.

OBJECTIVE: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS). METHODS: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups. RESULTS: Patient preoperative variables were comparable between the two groups, with no significant difference (P > 0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group (P = 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P = 0.010). The stone-free rates after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively (P = 0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7% (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up (P = 0.175); the rates of complications in the 2 groups were 19.0% (4/21) and 13.3% (2/15), respectively (P = 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group (P = 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group; however, the distributions in the F-URS group were 46.7% (7/15) and 53.3% (8/15), respectively (P = 0.310). CONCLUSION: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.

Long intergenic non-coding RNA induced by X-ray irradiation regulates DNA damage response signaling in the human bronchial epithelial BEAS-2B cell line.

Long non-coding RNAs (lncRNAs) have been regarded as the primary genetic regulators of several important biological processes. However, the biological functions of lncRNAs in radiation-induced lung damage remain largely unknown. The present study aimed to investigate the potential effects of lncRNAs on radiation-induced lung injury (RILI). Female C57BL/6 mice were exposed to 12 Gy single doses of total body irradiation (TBI). LncRNA microarray screening was conducted at 24 h post-irradiation (IR) to investigate the differentially-expressed lncRNAs during RILI. Following the subsequent bioinformatics analysis and reverse transcription-polymerase chain reaction (RT-PCR) validation, one of the verified differentially-expressed long intergenic radiation-responsive ncRNAs (LIRRs), LIRR1, was selected for further functional study. The normal human bronchial epithelial BEAS-2B cell line was used as the cell model. The recombinant eukaryotic expression vector for the lncRNA was designed, constructed and transfected using lipofectamine. RT-PCR, clonogenic and flow cytometry assays, immunofluorescence detection and western blot analysis were performed to reveal the role of the lncRNA in the radiosensitivity regulation of the RILI target cells. In lung tissues 24 h after 12 Gy TBI, six of the identified differentially-expressed LIRRs near the coding genes were validated using quantitative (q)PCR. The upregulation of two LIRRs was observed and confirmed using qPCR. LIRR1 was chosen for further functional study. Following the stable transfection of LIRR1, identified through G418 screening, increased radiosensitivity, evident cell cycle G1 phase arrest and increased γ-H2AX foci formation were observed in the bronchial epithelial BEAS-2B cell line subsequent to IR. LIRR1 overexpression also led to decreased expression of the KU70, KU80 and RAD50 DNA repair proteins, marked activation of p53, decreased mouse double minute 2 homolog (MDM2) expression, and substantially induced p21 and suppressed cyclin-dependent kinase 2 in BEAS-2B following IR. Subsequent to the use of Pifithrin-α, a specific inhibitor of p53 activation, increased MDM2 expression was observed in the LIRR1-overexpressing cells, suggesting that LIRR1 could mediate the DNA damage response (DDR) signaling in a p53-dependent manner. The present study provides a novel mechanism for RILI, using the concept of lncRNAs.

Changes in the adhesion and migration ability of peripheral blood cells: potential biomarkers indicating exposure dose.

The expression of adhesion molecules and their related functions of adhesion and migration were investigated in peripheral blood mononuclear cells (PBMCs) to identify radiation-related changes and dose-dependency. The authors screened new biomarkers as radiation exposure dose indicators. Heparinized human peripheral blood was irradiated in vitro with different doses of γ-rays. The expression levels of the CD11a, CD11b, CD18, CD29, CD49d, and CD54 molecules on the surface of PBMC cells were determined by flow cytometry at different time points post-irradiation. The adhesion ability of human PBMCs was determined using an enzyme-linked immunoassay kit, and the migration ability of rat PBMCs was evaluated using a transwell chamber assay. Compared with the unirradiated control group, a significant increase (p < 0.05) in human CD11b/CD13 double-positive cells was detected 6 h post 6 Gy irradiation in vitro. These results indicated that the decrease in human CD29/CD13 double-positive cells in the 6 Gy exposure group at 6, 12, and 24 h post-irradiation was significant (p < 0.01). The adhesion ability of irradiated human PBMCs to IgG substrate increased significantly (p < 0.05) at 6 h after irradiation of 2, 4, or 6 Gy compared with non-irradiated controls. The migration ability of the rat PBMCs toward the MIP-1α chemokine significantly decreased (p < 0.05) with increasing irradiation doses. These results suggest that the protein expression of cell surface molecules and their associated cellular functions might be potential biomarkers for identifying radiation exposure doses in an emergency radiation accident.

MiR-34a regulates apoptosis in liver cells by targeting the KLF4 gene.

MicroRNAs (miRNAs) regulate gene expression by inhibiting translation or targeting messenger RNA (mRNA) for degradation in a posttranscriptional fashion. In this study, we show that ectopic expression of miR-34a-5p reduces the mRNA and protein levels of Krüppel-like factor 4 (KLF4). We also demonstrate that miR-34a targets the 3'-untranslated mRNA region of KLF4 and show that overexpression of miR-34a induces a significant level of apoptosis in BNL CL.2 cells exposed to doxorubicin or 10 Gy X-ray. Our data suggest that the effects of miR-34a on apoptosis occur due to the downregulation of KLF4.

Radon-induced alterations in micro-RNA expression profiles in transformed BEAS2B cells.

Radon and its progeny are confirmed to be type I carcinogenic agents accounting for increased risks in 10% of observed lung cancers globally. However, the underlying carcinogenic mechanisms are largely unknown. In the present study, BEAS2B cells were directly exposed twice to 20,000 Bq/m(3) radon gas for 20 min once (first passage) and subsequently 10 times (fifth passage). The fifth-passage cells were then subcultured for 1 and 20 generations (named Rn5-1 and Rn5-20, respectively). Molecular mechanisms indicative of malignant transformation were assessed by determination of apoptosis, seroresistance, and microRNA (miRNA) expression profiles. The microRNA profiles were used to assess the functional annotations of the target genes. Data indicated an increased seroresistance and colony efficiency on soft agar, and enhanced apoptosis resistance in the Rn5-20 cells with significant differential expressions in some miRNA, including hsa-miR-483-3p, hsa-miR-494, hsa-miR-2115*, hsa-miR-33b, hsa-miR-1246, hsa-miR-3202, hsa-miR-18a, hsa-miR-125b, hsa-miR-17*, and hsa-miR-886-3p. Functional annotation demonstrated that these miRNA target genes were predominantly involved in the regulation of cell proliferation, differentiation, and adhesion during the process of malignant transformation, which is associated with signal pathways such as mitogen-activated protein kinase (MAPK), Int and Wg (Wnt), reactive oxygen species (ROS), nuclear factor κB (NF-κB), and other genes regulating cell cycles.

Variants on ESR1 and their association with prostate cancer risk: a meta-analysis.

BACKGROUND: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. METHODS: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. RESULTS: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). CONCLUSIONS: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.