Genetic Analysis of Hereditary Prostate Cancer

Study Overview
=================
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.

Official Title
-----------------
Genetic Analysis of Hereditary Prostate Cancer

Conditions
-----------------
Prostate Cancer

Participation Criteria
=================
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: A cluster of 3 or more first degree relatives, such as a father and 2 sons or 3 brothers The occurrence of prostate cancer in each of 3 generations in either the proband's paternal or maternal lineages Two first or second-degree relatives affected at an early age (age 55 years or younger).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Specimens<br>Specimens | |

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Genotyping, Linkage Analysis, Adenocarcinoma, Micro Satellite, Hereditary, Prostate Cancer (hereditary)