Clinical trial NCT00001469: Genetic Analysis of Hereditary Prostate Cancer
Official title: Genetic Analysis of Hereditary Prostate Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostate Cancer
Keywords: Genotyping
Linkage Analysis
Adenocarcinoma
Micro Satellite
Hereditary
Prostate Cancer (hereditary)
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 1999-11-04
Enrollment: 7776
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Existing specimens

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.

Eligibility criteria: * 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).

Primary outcomes:
measure: A
timeFrame: Ongoing
measure: B
timeFrame: Ongoing
measure: C
timeFrame: Ongoing
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Translational Genomics Research Institute
state: Arizona
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: New Orleans
country: United States
facility: Louisiana State University
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center, 9000 Rockville Pike
state: Maryland
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Tampere
country: Finland
facility: Tampere University
Study officials:
affiliation: National Human Genome Research Institute (NHGRI)
name: Joan Bailey-Wilson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Bishop JM. The molecular genetics of cancer. Science. 1987 Jan 16;235(4786):305-11. doi: 10.1126/science.3541204.
citation: Knudson AG Jr. Hereditary cancer, oncogenes, and antioncogenes. Cancer Res. 1985 Apr;45(4):1437-43. No abstract available.