Androgen deprivation therapy may reduce the risk of primary open-angle glaucoma in patients with prostate cancer: a nationwide population-based cohort study.
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ABSTRACT: Background
We evaluated the risk of developing primary open-angle glaucoma (POAG) according to androgen deprivation therapy (ADT) status in patients with prostate cancer.Materials and methods
From the nationwide claims database in South Korea, 218,203 men with prostate cancer were identified between 2008 and 2017. After applying the inclusion and exclusion criteria, a total of 170,701 patients (42,877 in the ADT and non-ADT groups and 127,824 in the non-ADT group) were included in the analysis. To adjust for comorbidities between cohorts, exact matching was performed. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of POAG associated with ADT after controlling for potential confounding factors.Results
In the matched cohort, the ADT group had a lower proportion of newly developed POAG than the non-ADT group (2.10% vs. 2.88%, respectively; P < 0.0001). Multivariable analysis revealed that the ADT group had a significantly lower risk of POAG than the non-ADT group (HR, 0.808; 95% CI, 0.739-0.884; P < 0.0001). The risk of POAG was lower in patients who underwent ADT for less than 2 years (HR, 0.782; 95% CI, 0.690-0.886; P = 0.0001) and in those receiving ADT for over 2 years (HR, 0.825; 95% CI, 0.744-0.916; P = 0.0003) compared with the non-ADT group.Conclusions
The use of ADT was associated with a decreased risk of POAG in Korean patients with prostate cancer. Our findings suggest that testosterone may be involved in the pathophysiology of POAG, and this should be confirmed through further studies.
SUBMITTER: Ahn HK
PROVIDER: S-EPMC8740392 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeThis study assessed the relationship between newly developed normal-tension glaucoma (NTG) and androgen deprivation therapy (ADT) in patients with prostate cancer.Materials and methodsA retrospective population-based cohort study was performed. During the period between 2008 and 2017, a total of 218203 prostate cancer patients were identified in a nationwide claims database in the Republic of Korea. The final analysis included 170874 patients (42909 in the ADT group, 127965 in the control group) after applying the inclusion and exclusion criteria. The incidences of NTG according to ADT duration were compared with controls. Exact matching was conducted to adjust comorbidities between cohorts. Cox proportional hazard regression models were performed after controlling for latent confounding factors, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of NTG according to ADT were obtained.ResultsIn the matched cohort, the ADT group was associated with a significantly reduced risk of NTG in multivariable analysis compared to the control group. The risk of NTG decreased in patients who underwent ADT for less than 2 years (HR=0.824; 95% CI, 0.682-0.995; p=0.0440) and in those using ADT over 2 years (HR=0.796; 95% CI, 0.678-0.934; p=0.0051), compared to the controls.ConclusionMedical castrations for patients with prostate cancer results in a lower incidence of newly diagnosed NTG compared to no ADT. These findings suggest that testosterone may be involved in the pathogenesis of NTG.
| S-EPMC9520039 | biostudies-literature
Project description:A substantial fraction of glaucoma has a genetic basis. About 5% of primary open angle glaucoma (POAG) is currently attributed to single-gene or Mendelian forms of glaucoma (ie glaucoma caused by mutations in myocilin or optineurin). Mutations in these genes have a high likelihood of leading to glaucoma and are rarely seen in normal subjects. Other cases of POAG have a more complex genetic basis and are caused by the combined effects of many genetic and environmental risk factors, each of which do not act alone to cause glaucoma. These factors are more frequently detected in patients with POAG, but are also commonly observed in normal subjects. Additional genes that may be important in glaucoma pathogenesis have been investigated using quantitative traits approaches. Such studies have begun to identify genes that control the magnitude of important quantitative features of glaucoma that may also be important risk factors for POAG, such as central corneal thickness. Each of these different approaches to study glaucoma genetics is providing new insights into the pathogenesis of POAG.
| S-EPMC3171270 | biostudies-literature
Project description:AimTo estimate the risk of blindness with primary angle-closure glaucoma (PACG) compared to primary open-angle glaucoma (POAG) in those population-based studies that reported blindness rates for both PACG and POAG.MethodA systematic search was performed in PubMed for articles published in English between 2000 and 2020 reporting the prevalence of POAG as well as PACG among various ethnic populations. A study was included if it was (1) population-based (2) had published prevalence and blindness rates for both PACG and POAG in the same cohort. (3) Glaucoma was defined as per the International Society for Geographical and Epidemiological Ophthalmology (ISGEO) criteria. The proportion of blindness for both POAG and PACG for each study and the cumulative proportion taking all the studies were calculated.ResultsWe included 23 studies with 78,434 participants. POAG was diagnosed in 1702 persons with 151 (8.9%) blind. There were 724 cases of PACG with 196 (27.0%) blind. The risk ratio of blindness in PACG to POAG varied from 0.73 to 10.6 among the studies. The cumulative risk ratio was 2.39 (95% confidence interval (CI); 1.99, 2.87). Risk ratios for studies including visual field restriction while defining blindness were similar to studies that did not (1.92 vs 2.64, P = 0.11). Risk ratios were also similar for studies that used greater than 2 instead of 3 or more quadrants of iridotrabecular contact to define angle closure (2.79 vs 2.25).ConclusionPrimary angle-closure disease is more likely to be associated with blindness.
| S-EPMC9582001 | biostudies-literature
Project description:PurposeTo understand the impact of socioeconomic status (SES) on the diagnosis of primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) in Taiwan.MethodsSubjects with glaucoma were identified from the National Health Insurance Research Database of year 2006, which included one million randomly selected insurants. Individuals who had ?4 ambulatory visits within one year which had the diagnosis code of POAG (ICD-9-CM 365.11 or 365.12) or PACG (365.23) and concurrent prescription of anti-glaucoma medication or surgery were selected. Individual SES was represented by monthly income calculated from the insurance premium. Neighborhood SES was defined based on neighborhood household income averages. Urbanization level of habitation was categorized into 3 levels. The odds ratio of having POAG or PACG in subjects with different SES was evaluated by using multiple logistic regression analysis.ResultsIn total, 752 and 561 subjects with POAG and PACG, respectively, who were treated on a regular basis, were identified. The diagnosis of glaucoma was affected by age, gender, frequency of healthcare utilization, individual SES, and urbanization level of habitation. With the adjustment of age, gender, healthcare utilization, neighborhood SES and level of urbanization, subjects with lower income were more likely to be diagnosed as PACG, but less likely as POAG.ConclusionsSubjects with more frequent healthcare utilization were more likely to be diagnosed with glaucoma. Subjects with low SES were more susceptible to PACG, but subjects with high SES were more likely to be diagnosed as POAG. This information is useful for the design and target participant setting in glaucoma education and screening campaign to maximize the efficacy of limited resources in preventing glaucoma blindness.
| S-EPMC4764499 | biostudies-literature
Project description:The total RNA from control and POAG optic nerve lamina cribrosa region was isolated and subjected to analysis on U133A 2.0 affymetrix microarray chip. The results from these two analysis was compared to determine whether PAD II RNA level is altered. Purpose of the study. This study was done to determine which RNA transcripts undergo significant changes in the optic nerve between normal and cadaver primary open-angle glaucoma donors. Using donor tissues from NDRI we have performed proteomic analyses (which will be published shortly), we intend a comparison between the proteomic and RNA changes for select proteins in our study. Sample Collection and Preparation of Labeled Copy RNA; The total RNA from optic nerve was obtained using TRIZOL (Invitrogen Inc., Carlsbad, CA) with modification of recommended protocols. The optic nerve from donor eyes were carefully excised and minced into small pieces first using a scissor and then a scalpel. Prior to use tissue was washed with DEPC water and all solutions were prepared in DEPC water. The minced tissue was placed in a glass homogenizer with 1 ml TRIZOL per 100 mg of tissue and homogenized in a glass homogenizer DUALL 20 (Kimble Kontes Glass Co, Vineland, NJ) with 10 strokes cycles each at room temperature and after freezing with liquid nitrogen for 1 min for 40 cycles. This RNA was extracted with chloroform, isoamylalcohol and precipitated with sodium citrate/sodium chloride and isopropanol. The final air-dried RNA precipitate was suspended in DEPC water and stored in â??80oC prior to use. RNA was prepared for hybridization according to the GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA). The hybridization was performed at Gene Expression Array Core Facility at Case Western Reserve University (www.geacf.net). The RNA sample was cleaned using a column from a Qiagen RNeasy kit, (part # 74104 ) in accordance with the manufacturerâ??s instructions. The volume of DEPC water used to elute the RNA from the Qiagen column was dictated by the nominal mass of the loaded RNA sample. Samples were eluted in 100ml of water, precipitated with 0.5 volume of 7.5M Ammonium Acetate and 2.5 volumes of 100% ethanol at -20oC for 1 hr and centrifuged for 10 min at room temperature. The pellet was drained and washed twice in 500µl of 70% ethanol. Supernatant was aspirated. The pellet was dried briefly (less than 1 min) in a speeedvac (Savant) and re-suspended in a small volume (~ 12â??15ml) of DEPC water. A small aliquot (2ml) of the sample was used for quantitation. Cleaned RNA samples were annotated as â??clnRNAâ?? and stored at -20oC. cDNA Synthesis; The protocol recommended by Affymetrix Inc. for cDNA synthesis was used at all times. The reaction was primed by annealing an oligo-dT primer coupled to a T7 RNA polymerase promoter to the RNA sample. Whenever possible, 8 mg of clnRNA were reverse transcribed using Superscript II reverse transcriptase in a 20ml reaction at 42oC for 1 hr. Second strand synthesis was carried out immediately in a total reaction volume of 150ml in the presence of E. coli DNA polymerase I, RNAse H and DNA ligase. The reaction mixture incubated for 2 hrs at 16oC and for a further 5 min in the presence of T4 DNA pol.. The reaction was terminated by the addition of EDTA. The sample was cleaned with a Qiagen cDNA clean-up column according to the manufacturers directions. The elution buffer volume was 14ml. The eluted samples were stored overnight at -20oC. In-Vitro Transcription (IVT) reaction; In a 0.5ml microfuge tube, complementary RNA (cRNA) was generated in an IVT reaction using a BioArray High Yield ENZO kit (Affymetrix). The 40ml reaction contained 10ml of cDNA sample and was incubated at 37oC in the heating block for 4-5hrs. Samples were mixed by flicking, pulse-centrifuged and returned to the incubator once every 40 minutes. Upon completion of the reaction, IVT samples were adjusted to a volume of 100ml with DEPC-treated water and cleaned using Qiagen RNA clean-up columns. Samples were eluted in 45ml of DEPC-treated water. A 2ml-aliquot was used for quantitation. Corrected concentrations of cRNA (minus the input clnRNA) were determined. A standard fragmentation reaction volume was 40ml in a 0.5 ml microfuge tube and used 20mg of overall IVT RNA in 1X fragmentation buffer (40mM Tris acetate, pH 8.1, 100mM KOAc, 30mM MgOAc). The reaction was incubated at 94oC for 35min in a heat block. After the 35 min incubation the fragmented samples were placed on ice. The standard hybridization cocktail volume was 300ml. 150ml of 2X hybridization buffer was added (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20) Herring sperm and acetylated BSA were added to a final concentration of 0.1 and 0.5mg/ml respectively. The amount of fragmentation reaction containing 15mg of cRNA was added to the cocktail and the remaining volume was made up with molecular biology grade water. A 15ml aliquot of a 20X mixture of in-vitro transcripts of bacterial genes BioB BioC BioD and cre as external controls (spikes) were added to the cocktail to give final concentrations of 1.5, 5, 25 and 100pM respectively. Control oligonucleotide (5ml) was added to a final concentration of 50pM. Array Hybridization; Sample Hyridization cocktails (300ml) were removed from storage at â??20oC and thawed in a 45oC temperature block. The samples were incubated at 45oC for 5 min, incubated at 45oC for 5 min and then centrifuged at 15,000g for 5 min. This study used commercially available Affymetrix HG U133A 2.0 arrays only. These are in situ synthesized, high density oligonucleotide arrays which can interrogate 22,777 gene entities. The part number is 900444 more detailed information may be found at www.affymetrix.com website. Meanwhile, the affymetrix chip arrays were taken from their storage at 4oC and allowed to come to room temperature. The chamber was filled with 1X hybridization buffer (final concentrations : 100mM MES, 1M [Na+], 20mM EDTA, 0.01% Tween 20). The chip was then preconditioned by incubation in the hybridization oven at 45oC for 10 min. The chip was removed and the chamber drained. Sample cocktails (200ml) were then introduced into the chamber of the chips. The ports were sealed with tough-spots stickers and placed in the hybridization oven and incubated at 45oC with rotation overnight. Next day (16hr later), the incubation was terminated and the chips removed from the oven. Samples were retrieved from the chips and stored again in a freezer at -20oC. The chips were filled with buffer A and placed in a module of Fluidics 400 wash station. The chips were subjected to the Affymetrix â??EuKws4 ver 2â?? programmed series of stringent post hybridization washes, staining and post-staining washes in accordance with Affy protocols. Upon completion of the wash series (approximately 2 hrs), the chips were removed from the Fluidics station. The chips were inspected. Chips were scanned using an Agilent Gene Array scanner 3000 driven by Affymetrix GCOS software. Generation of Expression Values; Microarray Suite, version 5 (Affymetrix), was used to generate *.cel files, and a computer program (Probe Profiler, ver. 1.3.11; Corimbia Inc., Berkeley, CA) developed specifically for the GeneChip system (Affymetrix) was used to convert intensity data into quantitative estimates of gene expression for each probe set. The software identifies informative probe pairs, and down-weights the signal contribution of probe pairs that are subject to differential cross-hybridization effects or that consistently produce no signal. The software also detects and corrects for saturation artifacts, outliers, and chip defects. A probability statistic was generated for each probe set. The probability is associated with the null hypothesis that the expression level of the probe set is equal to zero (background). Genes not significantly expressed above background in any of the samples (P > 0.05) were
2008-06-12 | E-GEOD-2387 | biostudies-arrayexpress
Project description:PURPOSE:To determine the relationship between positive family history (FH) and primary open-angle glaucoma (POAG) diagnosis and clinical presentation in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) cohort. METHODS:FH of POAG in first-degree relatives was assessed in 2365 subjects in the POAAGG cohort. A standardized interview was used to assess FH of glaucoma, demographic characteristics, lifestyle choices, and medical and ocular comorbidities. RESULTS:Positive FH was associated with increased risk of POAG (age-adjusted odds ratio and 95% confidence interval 3.4 [2.8, 4.1]). In age-adjusted analysis among POAG cases, positive FH was associated with younger age (P < .001), female sex (P < .001), hypertension (P = .006), use of hypertension medication (P = .03), and prior glaucoma surgery (P = .02). Cases with positive FH also had thicker retinal nerve fiber layers (P = .03). CONCLUSIONS:The risk conferred by positive FH suggests strong genetic underpinnings for some patients with this disease, which will be investigated by genome-wide association studies and whole exome sequencing. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
| S-EPMC6064667 | biostudies-literature
Project description:Long non-coding RNAs were associated with the development and progression of glaucoma. Our study aim to identify the potential genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).
2019-09-28 | GSE138125 | GEO
Project description:This study aimed to investigate the molecular mechanism responsible for primary open-angle glaucoma (POAG) progression. We analyzed microRNAs (miRNAs) expression profiling in aqueous humor (AH) of both POAG patients and normal controls, using a microarray-based approach. Subsequently, differentially expressed miRNAs (DEmiRNAs) were identified using Bayes moderated t-test. Next, DEmiRNAs target genes were predicted based on miRNA databases, followed by GO analysis and pathway analysis using DAVID. Furthermore, OAG-related genes analysis for target genes was carried out using CTD database, respectively. Finally, verification of DEmiRNAs expression levels was performed by RT-qPCR. A total of 40 significant DEmiRNAs were identified between control and POAG groups, including 24 up-regulated miRNAs and 16 down-regulated miRNAs. Further, the target genes of hsa-miR-206, including BMP2, SMAD4, ID2, and TNF, were mainly enriched in transforming growth factor-β (TGF-β) signaling pathway. While, target genes of hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p, including BCL2, EPHB2, VEGFA, COL4A1, APC, and TGFBR1, were enriched in eye development. Moreover, FNDC3B, CAV2 and VEGF, target genes of hsa-miR-206 or hsa-miR-34c-5p, were the OAG-related genes. Ultimately, RT-qPCR analysis confirmed that mRNA levels of hsa-miR-206, hsa-miR-7-2-3p, and hsa-miR-20b-3p were increased, while those of hsa-miR-184 and hsa-miR-34c-5p were decreased in POAG compared with normal groups (P < 0.05). Hsa-miR-206, hsa-miR-184, hsa-miR-34c-5p, hsa-miR-7-2-3p and hsa-miR-20b-3p might play a significant role in the pathogenesis of POAG and hsa-miR-206 might be associated with the development of POAG by regulating TGF-β signaling pathway. These results might provide insight toward a better understanding of the pathogenesis of POAG.
2015-08-04 | GSE71639 | GEO
Project description:PURPOSE:This study sought to investigate the role of rare copy number variation (CNV) in age-related disorders of blindness, with a focus on primary open-angle glaucoma (POAG). Data are reported from a whole-genome copy number screen in a large cohort of 400 individuals with POAG and 500 age-matched glaucoma-free subjects. METHODS:DNA samples from patients and controls were tested for CNVs using a combination of two microarray platforms. The signal intensity data generated from these arrays were then analyzed with multiple CNV detection programs including CNAG version 2.0, PennCNV, and dChip. RESULTS:A total of 11 validated CNVs were identified as recurrent in the POAG set and absent in the age-matched control set. This set included CNVs on 5q23.1 (DMXL1, DTWD2), 20p12 (PAK7), 12q14 (C12orf56, XPOT, TBK1, and RASSF3), 12p13.33 (TULP3), and 10q34.21 (PAX2), among others. The CNVs presented here are exceedingly rare and are not found in the Database of Genomic Variants. Moreover, expression data from ocular tissue support the role of these CNV-implicated genes in vision-related processes. In addition, CNV locations of DMXL1 and PAK7 overlap previously identified linkage signals for glaucoma on 5p23.1 and 20p12, respectively. CONCLUSIONS:The data are consistent with the hypothesis that rare CNV plays a role in the development of POAG.
| S-EPMC3207715 | biostudies-literature
Project description:Purpose of review:Individuals of African descent are at highest risk for developing primary open-angle glaucoma (POAG), a devastating disease and major contributor of blindness worldwide. Currently, there is a large dearth of knowledge in this area despite a critical need for better understanding the underlying genetic and environmental factors afflicting this population. Here we highlight the current literature exploring the genetics of POAG in African Americans. Recent findings:Current studies have yet to replicate European POAG index variants (i.e. CDKN2B-AS1 and SIX1/SIX6) in African Americans or to definitely exclude that these loci contribute to risk in African descent populations. Recent studies have evaluated clinical features that may account for some differences in POAG risk between African Americans and European Americans. Summary:In summary, little headway has been made in elucidating the genetics of primary open-angle glaucoma in African Americans and other individuals of African descent.
| S-EPMC5739069 | biostudies-literature