Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Genetic Predisposition to Disease

Disease Susceptibility

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Subjects with histologically confirmed prostate cancer and genomic testing results

Subjects with histologically confirmed prostate cancer who deemed to be an exceptional responder with or without genomic testing results

Katherine O Lee-Wisdom, R.N.

Fatima H Karzai, M.D.

Audrey Dinh

Kaitlin Zablotsky

Fatima Karzai, M.D.

Xin Gao

Dory Freeman

Arul Chinnaiyan

Ashley Regazzi

William Oh

Cora Sternberg

Julie Graff

Kamilah Taylor

Joaquin Mateo

Background:

Prostate cancer is the most common cancer and the second leading cause of death in males in the United States. Researchers want to find additional gene mutations that may increase a man s risk for prostate cancer and may affect how aggressive the disease is.

Objective:

To look at gene mutations in men with prostate cancer as well as the course of their disease to better understand how gene mutations relate to the way the cancer progresses and responds to treatment.

Eligibility:

Adult males 18 and older with prostate cancer who have at least one of the gene mutations researchers want to study and/or have been treated for their cancer and have had complete elimination of their cancer or stable disease for a long time.

Design:

Participants will be screened with a review of their medical records. Their gene test results will be reviewed, if available. They will be asked questions over the phone or in person.

Participants do not need to visit the NIH for this study. But if they visit NIH for another study, their data and test results will be collected. They may give blood and urine samples. They may give leftover tumor samples. These samples will be used to study their genes.

Participants who do not come to NIH on regular basis will be contacted every 6 months by phone or e-mail. They will be asked questions about their health. Data from their medical records will be collected.

Participants will have testosterone and prostate-specific antigen (PSA) tests.

Participants may be invited to NIH to give blood samples for research.

Participants on this study will be followed for life.

Background:

* Prostate cancer is the most common cancer and the second leading cause of death in males in the United States with an estimated 191,930 new cases and 33,330 deaths in 2020.
* There has been progress in identifying established risk factors for the development of prostate cancer, including genetic predisposition. The study of the molecular genetics of prostate cancer has identified pathogenic variants, such as BRCA1 and BRCA2 (associated with hereditary breast and ovarian cancer syndrome), HOXB13 (associated with hereditary prostate cancer), and DNA mismatch repair (MMR) gene variants (MLH1, MSH2, MSH6, PMS2, and EPCAM) associated with Lynch syndrome.
* While our understanding of molecular genetics continues to grow, there remains a need to identify additional germline and somatic mutations and alterations that may increase an individual s risk to develop prostate cancer and potentially the aggressiveness of the disease. In studying the following alterations in prostate cancer, in both localized and advanced stages, potential expanded molecular findings may lead to actionable therapeutic targets and biomarker development. A better understanding of molecular genetics in a longitudinal study of subjects with prostate cancer may be helpful for the design of future treatment studies, and to develop a better understanding of the natural history of the disease

Objectives:

* To longitudinally evaluate subjects with prostate cancer with known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, CDK12, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM to better understand the natural history of the disease.
* To longitudinally evaluate subjects with tumor mutational burden-high (TMB-H) prostate cancer (greater than or equal to 10 mutations/megabase \[mut/Mb\] or blood TMB (bTMB) \[greater than or equal to16 mut/Mb\]).

Eligibility:

* Subjects with histologically confirmed prostate cancer
* Must have known germline and/or somatic variants in PIK3 and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, CDK12, and MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM and/or TMB-high or be deemed an exceptional responder. NOTE: any platform for genomics testing is acceptable (research or CLIA-certified)
* Age greater than or equal to 18 years old

Design:

* This will be a long-term multi-center study to comprehensively study participants with prostate cancer.
* Participants will provide clinical information (including medical history, clinical tests, imaging studies and reports, surgical pathology reports, genetic test results).
* Since long-term follow-up of individuals with prostate cancer is a major feature of the study, local sites intend to maintain active contact with study subjects for as long as possible. Participants will be followed throughout the course of their illnesses, with particular attention to patterns of disease recurrence and progression, response to therapies and duration of responses.

Precision-Based Genomics in Prostate Cancer

A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@ In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

clinical presentation, patterns of disease progression, therapeutic response, disease recurrence and participant overall survival

National Cancer Institute (NCI)

Heart and Blood Diseases

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Rare Diseases

Hypertension

Adenoma

Bone Diseases

Bone Diseases, Metabolic

Hyperaldosteronism

Hyperinsulinism

Adrenocortical Adenoma

Adrenal Gland Neoplasms

Metabolic Diseases

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Glucose Metabolism Disorders

Endocrine Gland Neoplasms

Adenoma of the Adrenal Gland

Hyperadrenalism

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Epinephrine

Racepinephrine

Epinephryl borate

Adult individuals (age 18 or older) with HTN and discrete adrenal masses or bilateral hyperplasia of the adrenal glands, with outpatient positive ARR or string clinical suspicion for PA

DNA from relatives of patients (age 7 or older)

Sanaz Sakiani, M.D.

Background:

The adrenal gland makes the hormone aldosterone. This helps regulate blood pressure. An adrenal gland tumor that makes too much aldosterone can cause high blood pressure and low potassium. The cause of these tumors is unknown, but sometimes they are inherited.

Objective:

To study the genes that may cause primary aldosteronism in Black individuals.

Eligibility:

People ages 18-70 who:

Are Black, African American, or of Caribbean descent

And have difficult to control blood pressure or primary aldosteronism

Relatives of people with primary aldosteronism

Design:

Participants who are relatives of people with primary aldosteronism will have only 1 visit, with medical history and blood tests.

Participants with primary aldosteronism or difficult to control blood pressure (suspected to possibly have primary aldosteronism) will be screened with a 1-2 hour visit. If they qualify, they will return for a hospital stay for 7-10 days. Tests may include:

Medical history

Physical exam

Blood tests: Participants will have a small tube (IV catheter) inserted in a vein in the arm. They may drink a glucose-containing liquid or get a salt solution. If medically indicated, they may have invasive blood tests with a separate consent.

Urine tests: Some require a high-salt diet for 3 days.

Heart tests

Scans: Participants lie in a machine that takes pictures of the body. A dye may be injected through a vein.

Small hair sample taken from near the scalp.

Kidney ultrasound

Bone density scan: Participants lie on a table while a camera passes over the body.

If the doctors feel it is medically necessary, they will offer participants treatment depending on their results. These treatments may cure the patient of their disease and may include:

1. Having one adrenal gland removed by the Endocrine surgeon under anesthesia. Patients will have follow-up visits 2-4 weeks after surgery.
2. Taking drugs to block the effects of aldosterone

Participants may return about 1 year later to repeat testing....

Primary Aldosteronism (PA) is the most common cause of secondary hypertension, accounting for 6-8% of hypertension and 14-25% of resistant hypertension. This prevalence translates to approximately 1 in 30-50 adults or about 4,000,000 Americans with PA. Until recently, the deleterious effects of PA were thought to derive solely from aldosterone-mediated sodium retention and associated blood pressure rise. However, animal studies and clinical trials demonstrate that mineralocorticoid receptor (MR) blockade has cardio- and reno-protective effects that clearly exceed those expected from blood pressure reduction alone. Growing evidence supports the concept that excess aldosterone, in the presence of elevated blood pressure, initiates a cascade characterized by fibrosis, oxidative stress, and activation of pro-inflammatory and pro-fibrotic pathways, leading to morbidity via worsened insulin sensitivity, impaired bone formation, and accelerated cardiovascular remodeling. Recent studies have identified several new genetic underpinnings of PA, both germline and somatic, including mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and ARMC5. As the effects of chronic hyperaldosteronism differ between races, it is not surprising that the relative prevalence of these mutations differs among cohorts. African Americans (AA) in particular have increased susceptibility to end-organ damage from aldosterone excess-induced cardiovascular remodeling. They are more likely to have congestive heart failure, end-stage renal disease, and atherosclerotic events than age-matched Caucasians. However, to date no comprehensive analysis of mutations in PA has been performed in AA. (Note: for the purposes of this protocol, the terms Black or African American incorporate individuals who self-identify as Black, African American, or the Caribbean diaspora).

The aims of this study are to identify the germline and/or somatic mutations causing PA in AA, define the effects of these mutations on aldosterone production in AA, and to identify effective pharmacologic agents that will inhibit inappropriate aldosterone production in target cells. Aldosterone producing adenoma (APA) and other adrenocortical tumor (ACT) specimens will be gathered from archival (collected under protocol 00-CH-160 and other related NIH studies) and prospective research subjects with PA that will be evaluated at the NIH Clinical Research Center under the proposed protocol. Samples will be analyzed using state-of-the-art next-generation sequencing (NGS). Human adrenal cell lines (H295R and others, as appropriate) will be used to study the mutations effect on aldosterone production. Additionally, this will help identify possible effective pharmacologic therapeutics to treat PA. Animal models of novel genetic causes of PA may also be created to study the molecular mechanisms underpinning the disease.

Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks

define the causes of PA in AA and develop new therapeutic strategies to inhibit the inappropriate aldosterone production.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study title	NCT ID	Conditions	Eligibility	Organization
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer	18 Years -	National Institutes of Health Clinical Center (CC)
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer	18 Years -	National Institutes of Health Clinical Center (CC)
Clinical and Molecular Characteristics of Primary Aldosteronism in Blacks	NCT03374215	Adrenal Gland N... Hypertension Bone Diseases, ... Cardiovascular ... Hyperinsulinemi...	7 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer	18 Years -	National Institutes of Health Clinical Center (CC)

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