Genetic Analysis of Hereditary Prostate Cancer

Completed

• Conditions: Prostate Cancer

• Registration Number: NCT00001469
• Lead Sponsor: National Human Genome Research Institute (NHGRI)

Brief Summary

Molecular approaches to the understanding of human neoplastic disease have revealed that multiple genetic alterations are an essential component of tumorigenesis. Both germline and somatic genetic alterations can be involved in the malignant transformation of normal cells. Identification of the genes involved in neoplastic transformation has been approached through the molecular analysis of sporadic cancers and the genetic study of families with an inherited predisposition for cancer. The interplay of these two approaches has led to the characterization of genes such as the retinoblastoma (Rb) gene, the p53 gene and the adenomatous polyposis coli (APC) gene that are all involved in the development of both hereditary and non-hereditary forms of cancer. Inherited mutations in such genes predispose affected families to hereditary cancer syndromes, affording an opportunity to identify genetic lesions that also cause the more common sporadic cancers.

Prostate cancer (PRCA) is the most common cancer diagnosed (1999 estimate 179,300 cases) and the second leading cause of cancer mortality (1999 estimate 37,000 deaths) in men in the United States. Family history is the single strongest risk factor currently known for prostate cancer. This raises the possibility that heritable genetic factors may be involved in the development of this disease in a subset of men. The genetic contribution to diseases of complex origin such as cancer is often most salient in families of early onset cases. Therefore, prostate cancer inheritance following a simple Mendelian pattern may be identified in the families of probands with early-onset cases. Common susceptibility alleles of small effect may be detectable in families with later-onsent and/or less strong family history of PRCA or in case-control data.

Detailed Description

Molecular approaches to the understanding of human neoplastic disease have revealed that multiple genetic alterations are an essential component of tumorigenesis. Both germline and somatic genetic alterations can be involved in the malignant transformation of normal cells. Identification of the genes involved in neoplastic transformation has been approached through the molecular analysis of sporadic cancers and the genetic study of families with an inherited predisposition for cancer. The interplay of these two approaches has led to the characterization of genes such as the retinoblastoma (Rb) gene, the p53 gene and the adenomatous polyposis coli (APC) gene that are all involved in the development of both hereditary and non-hereditary forms of cancer. Inherited mutations in such genes predispose affected families to hereditary cancer syndromes, affording an opportunity to identify genetic lesions that also cause the more common sporadic cancers.

Prostate cancer (PRCA) is the most common cancer diagnosed (1999 estimate 179,300 cases) and the second leading cause of cancer mortality (1999 estimate 37,000 deaths) in men in the United States. Family history is the single strongest risk factor currently known for prostate cancer. This raises the possibility that heritable genetic factors may be involved in the development of this disease in a subset of men. The genetic contribution to diseases of complex origin such as cancer is often most salient in families of early onset cases. Therefore, prostate cancer inheritance following a simple Mendelian pattern, may be identified in the families of probands with early-onset cases. Common susceptibility alleles of small effect may be detectable in families with later-onset and/or less strong family history of PRCA or in case-control data.

Study Timeline

• Study Start: 1995-01-01
• Study First Submitted: 1999-11-03
• Study First Submitted QC: 1999-11-03
• Study First Posted: 1999-11-04
• Primary Completion: 2009-07-17
• Study Completion: 2009-07-17
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-13
• Last Update Posted: 2020-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7776

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
A	Ongoing	To identify by genetic mapping the existence of loci responsible for hereditary prostate cancer.
B	Ongoing	To identify and characterize the gene(s) within the identified regions above, which are involved in the etiology of hereditary prostatecancer.
C	Ongoing	To study the role of the above gene(s) in the initiation or progression of prostatic neoplasia.

Trial Locations

Locations (8)

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States

Tampere University; 🇫🇮 Tampere, Finland

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

Translational Genomics Research Institute; 🇺🇸 Phoenix, Arizona, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Louisiana State University; 🇺🇸 New Orleans, Louisiana, United States

Howard University Hospital; 🇺🇸 Washington, District of Columbia, United States