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)

Digestive System Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Colorectal Neoplasms

Nasopharyngeal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Variants of 139 genes associated with different hereditary cancers and polyposis were screened by next-generation sequencing.

germline variants

Ying Yuan, PhD

Dong Xu, PhD

Guoli Gu, MD

Daici Chen, PhD

Yanhong Gu, MD

Haixing Ju, MD

Ying Yuan, Ph.D & MD

Ying Yuan

Patients suspected of adenomatous polyposis were included. The criteria used were more than 10 polyps observed under colonoscopy, and pathological confirmation of adenoma. Clinical data and pedigree information were collected. The variants of 139 genes associated with different hereditary cancers and polyposis were screened by NGS, which was performed by Genetron Health on the HiSeqX-ten sequencing platform.

Multicenter Study on the Pathogenic Germline Gene Variants of Colorectal Polyposis in China

germline variant detection rate in the polyposis population

Second Affiliated Hospital, School of Medicine, Zhejiang University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer		18 Years -	National Institutes of Health Clinical Center (CC)
Multicenter Study on the Pathogenic Germline Gene Variants of Colorectal Polyposis in China	NCT04961125	Colorectal Poly...	germline varian...	-	Second Affiliated Hospital, School of Medicine, Zhejiang University
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer		18 Years -	National Institutes of Health Clinical Center (CC)
Multicenter Study on the Pathogenic Germline Gene Variants of Colorectal Polyposis in China	NCT04961125	Colorectal Poly...	germline varian...	-	Second Affiliated Hospital, School of Medicine, Zhejiang University
Precision-Based Genomics in Prostate Cancer	NCT04706663	Prostate Cancer		18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for germline variants