Prostate Cancer Genetic Risk Evaluation and Screening Study
Ontology highlight
ABSTRACT:
DISEASE(S): Prostatic Neoplasms,Mmr Mutation,Lynch Syndrome,Prostatic Neoplasm,Atm Gene Mutation,Brca1 Mutation,Prostate Cancer,Genetic Predisposition To Disease,Colorectal Neoplasms, Hereditary Nonpolyposis,Brca2 Mutation
PROVIDER: 2396203 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Background:
Research studies have shown that genetic changes and family history may increase a man s risk for prostate cancer. Researchers want to follow the prostate health of men who have specific genetic changes associated with prostate cancer to help them learn more about which men are at higher risk for prostate cancer.
Objectives:
To study men with specific genetic changes and determine who is at higher risk for getting prostate cancer. To study if certain genetic changes and family history can be used to help prevent or treat prostate cancer.
Eligibility:
Persons assigned male at birth ages 30-75 who have one or more specific genetic changes but without prostate cancer.
Design:
* This study does not perform genetic testing. All participants must have documented genetic changes and able to provide a copy of the report.
* Before enrollment, participants will provide a copy of documented genetic changes and go through a telephone interview to determine eligibility for the study.
* On enrollment, participants will have medical and family history review, medication review, physical exam, blood collection for clinical and research testing, and MRI (magnetic resonance imaging) of the prostate.
* Every year, participants will repeat the physical exam, medical history, family history, medication review, routine blood tests, including PSA and testosterone.
* Every 2 years, participants will repeat all the above plus prostate MRI and blood tests for research.
* If, at any time, the physical exam, blood tests or MRI are abnormal, participants may be asked to do a biopsy.
* If the biopsy results in prostate cancer, participants will be given counseling on next steps, general treatment recommendations, and then followed with a phone call each year.
* Participants may ask to speak with a genetic counselor.
| 2294496 | ecrin-mdr-crc
Project description:There is a need to understand genetic and lifestyle factors that may influence the risk of cancer progression in men who have organ-confined prostate cancer and have chosen a programme of 'active surveillance' as opposed to radical treatment with the associated health risks. Epidemiological studies have suggested that consumption of cruciferous vegetables is associated with reduced risk of developing aggressive prostate cancer. In this study we recruited men on active surveillance for low- to intermediate-risk prostate cancer to determine whether a 12-month dietary intervention can elicit transcriptional or nmetabolic responses in their prostate that would be consistent with a reduction in the risk of progression. We undertook RNAseq on prostate biopsies collected before and after a 12-month intervention with broccoli soups.
2020-01-01 | E-MTAB-6525 | biostudies-arrayexpress
Project description:African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups. Experiment Overall Design: To identify cancer-specific gene expression patterns in AA men, we established primary prostate cancer epithelial cells from 14 AA and 13 EA men. Cells were cultured for RNA extraction and hybridization on Affymetrix microarrays.
2009-08-07 | E-GEOD-17356 | biostudies-arrayexpress
Project description:The primary objective of this study was to correlate genetic alterations from Hh pathway genes with biochemical free relapse rate. aCGH data of 126 intermediate risk men with histologically confirmed adenocarcinoma of the prostate who had chosen radical radiotherapy as their primary treatment between 1996-2006.
2012-09-28 | E-GEOD-41120 | biostudies-arrayexpress
Project description:Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective is to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.
2016-06-07 | GSE80683 | GEO
Project description:PSA screening has led to enormous overtreatment of prostate cancer, due to the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and most indeterminate in terms of prognosis. Using the complementary DNA (cDNA)M-bM-^@M-^Smediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (N=358) and PhysiciansM-bM-^@M-^Y Health Study (PHS; N=109). We developed an mRNA signature of Gleason comparing individuals with Gleason M-bM-^IM-$6 to those with Gleason M-bM-^IM-%8 tumors, and applied the model among Gleason 7 cases to discriminate lethal cases. We built a157-gene signature using the Swedish data that predicted Gleason with low misclassification (AUC=0.91); when this signature was tested in the PHS validation set, the discriminatory ability remained high (AUC=0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4+3 or 3+4 (p=0.006). Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment. 198 cases from the population-based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); expression profiles from tumors with Gleason M-bM-^IM-%8 (N=89) were compared to those from tumors with Gleason M-bM-^IM-$6 (N=109)
2012-04-30 | E-GEOD-37663 | biostudies-arrayexpress
Project description:Purpose: Patients with locally advanced prostate cancer after radical prostatectomy are candidates for secondary therapy. However, this higher risk population is heterogeneous. Many cases do not metastasize even when conservatively managed. Given the limited specificity of pathological features to predict metastasis, newer risk prediction models are needed. We report a validation study of a genomic classifier that predicts metastasis after radical prostatectomy in a high risk population. Method:A case-cohort design was used to sample 1,010 patients after radical prostatectomy at high risk for recurrence who were treated from 2000 to 2006. Patients had preoperative prostate specific antigen greater than 20 ng/ml, Gleason 8 or greater, pT3b or a Mayo Clinic nomogram score of 10 or greater. Patients with metastasis at diagnosis or any prior treatment for prostate cancer were excluded from analysis. A 20% random sampling created a subcohort that included all patients with metastasis. We generated 22-marker genomic classifier scores for 235 patients with available genomic data. ROC and decision curves, competing risk and weighted regression models were used to assess genomic classifier performance. Patients treated with RP between 2000 and 2006 were identified from the Mayo Clinic tumor registry for a case-cohort study design. This involved identification of all patients with metastasis and a representative of the full cohort .Thus, men at high risk of recurrence post-RP (open/robotic) with no prior neoadjuvant/prostate cancer treatment were selected based on any of preoperative PSA >20 ng/mL, pathological Gleason score (GS) â¥8, SVI, or GPSM (GS; preoperative PSA; SVI; margins) score â¥10.The cohort of 1,010 men included 73 cases with metastasis as evidenced by CT or bone scan. A 20% random sample (n=202) was drawn from the cohort. This included 19 of 73 metastatic cases. To increase sampling of metastasis, the remaining 54 metastatic cases were added, resulting in a final study set of 256 patients. 21 samples did not pass QC and were eliminated from this study. Patients not experiencing metastasis regardless of BCR (defined as follow-up PSA â¥0.4 ng/mL >30 days post-RP) were censored at last follow-up. The study was approved by Mayo Clinic Institutional Review Board.
2014-11-13 | E-GEOD-62116 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) is the leading cancer among men in the United States, with genetic factors contributing to ~42% of the susceptibility to PCa. To understand the causal genetic factors associated with PCa, we have focused on a PCa risk region located at 7p15.2. We performed Hi-C analysis and demonstrated that this region has long range interactions with the HOXA locus, located ~873 kb away. Using the CRISPR/Cas9 system, we deleted a 4 kb region encompassing several prostate cancer risk-associated SNPs and performed RNA-seq to investigate transcriptomic changes in RWPE1 prostate cells lacking the regulatory element. Our results suggest that the risk element affects the expression of HOXA13 and HOTTIP, but not other genes in the HOXA locus, via a repressive loop. Forced expression of HOXA13 was also performed to gain insight into the mechanisms by which this risk element affects prostate cancer risk.
2017-11-01 | GSE98898 | GEO
Project description:African-American (AA) men experience increased risk of developing prostate cancers as well as increased mortality following treatment as compared to European-American (EA) men. The aim of our study was to identify biological factors with potential to predispose AA men to prostate tumor progression and metastasis. High-throughput microarrays were used to investigate differences in global gene expression comparing the two groups.
2009-07-28 | GSE17356 | GEO
Project description:Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer deaths in men. GWAS studies have identified variants associated with prostate cancer susceptibility, however, mechanistic and functional validation of these mutations are lacking. Mitochondrial energy metabolism plays an important role in the onset and development of cancer. A missense variant was identified in the ELAC2 gene, which encodes a dually localized nuclear and mitochondrial RNA processing enzyme, with predicted impact on metabolism and tumorigenesis. We used CRISPR/Cas9 genome editing to introduce this variant into the mouse Elac2 gene as well as to generate a prostate-specific gene knockout of Elac2. The mutations caused enlargement and inflammation in the prostate and nodule formation. Multi-omic profiling revealed defects in RNA and energy metabolism that activated proinflammatory and tumorigenic pathways as a consequence of impaired processing of mitochondrial and nuclear encoded non-coding RNAs and reduced protein synthesis. The Elac2 variant or knockout mice on the background of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model show that Elac2 mutation with a secondary genetic insult exacerbated the onset and progression of prostate cancer and led to metastasis. Our systems biology analyses reveal a miRNA-mediated molecular mechanism by which specific non-coding RNAs elicit metabolic changes that drive prostate tumorigenesis and metastasis. We conclude that the ELAC2 variant is a predisposing factor for prostate cancer and provide a detailed molecular mechanism and physiologically relevant models of this cancer.
2023-04-19 | PXD033891 | Pride