Genetic Analysis of Hereditary Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Genetic Analysis of Hereditary Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00001469
• Other study ID #: 950158
• Secondary ID: 95-HG-0158
• Status: Completed
• Start date: January 1, 1995
• Est. completion date: July 17, 2009

Study information

• Verified date: March 2020
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7776
• Est. completion date: July 17, 2009
• Est. primary completion date: July 17, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• INCLUSION CRITERIA:

Enrollment in this study includes case-control data from men with prostate cancer and matched controls who are free from the disease, plus affected and unaffected individuals from families who meet the following criteria for Hereditary Prostate Cancer:

1. A cluster of 3 or more first degree relatives, such as a father and 2 sons or 3 brothers

2. The occurrence of prostate cancer in each of 3 generations in either the proband's paternal or maternal lineages

3. Two first or second-degree relatives affected at an early age (age 55 years or younger).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
Finland	Tampere University	Tampere
United States	Johns Hopkins University	Baltimore	Maryland
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Louisiana State University	New Orleans	Louisiana
United States	Translational Genomics Research Institute	Phoenix	Arizona
United States	Howard University Hospital	Washington	District of Columbia
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Countries where clinical trial is conducted

United States,  Finland, 

References & Publications (3)

Bishop JM. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305-11. Review. — View Citation

Ichikawa T, Ichikawa Y, Dong J, Hawkins AL, Griffin CA, Isaacs WB, Oshimura M, Barrett JC, Isaacs JT. Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosome 11. Cancer Res. 1992 Jun 15;52(12):3486-90. — View Citation

Knudson AG Jr. Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437-43. — View Citation

Outcome

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

External Links

•   NIH Clinical Center Detailed Web Page