Identification and Characterization of an X-Linked Familial Prostate Cancer Gene

• Main Author: Yaspan, Brian
• Other Authors: VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
• Format: Text
• Language: English
• Published: 2006
• Subjects: Genetic Engineering and Molecular Biology; Anatomy and Physiology; *GENES; *MALES; *LINKAGES; *EPIDEMIOLOGY; *PROSTATE CANCER; ENVIRONMENTS; RISK; CANCER; CAUCASIANS; ICELAND; FINLAND; GENETICS; PATIENTS; POPULATION; SHARING; SEGREGATION(METALLURGY); Iceland
• Online Access: http://www.dtic.mil/docs/citations/ADA463100; http://oai.dtic.mil/oai/oai?&verb=getRecord&metadataPrefix=html&identifier=ADA463100

There is a significant heritable component of prostate cancer. Increased familial relative risk is observed across multiple populations (European, Asian-American, African-American and Caucasian). Male first degree relatives of prostate cancer patients have a two- to three-fold increased risk. Segregation analyses support genetic rather than shared environmental risk. Twin cancer concordance studies reveal a higher heritable risk for prostate cancer than for any other common cancer. A Scandinavian study of 44,788 twin pairs estimated that 42% risk of prostate cancer is heritable; the concordance rate was 21% among monozygotic twins, and 6% among dizygotic twins. Large-scale US twin studies have revealed comparable concordance rates. Additional epidemiological studies have been consistent with X-linked transmission, identifying higher risk for a man with an affected brother relative to one with an affected father. Despite the overwhelming genetic predisposition evidence, the identification of prostate cancer susceptibility genes has been difficult. Linkage studies have resulted in the identification of several loci difficult to confirm across study populations. However, summary studies of genome-wide scans for prostate cancer susceptibility loci in general confirm two loci, HPC-1 and HPC-X. Our study seeks to identify a candidate gene or genes conferring prostate cancer susceptibility at locus HPC-X in a US Caucasian study population. We hypothesize that a gene or genes at HPC-X harbor common moderate-penetrance variants predisposing to prostate cancer, with a role much greater than that inferred through study of rare HPC families. We looked at shared haplotypes in founder populations and found two intervals likely to harbor prostate cancer susceptibility genes. We have chosen to first focus on one interval at locus HPC-X (termed HPC-X region A) due to shared haplotype association evidence in the founder populations of Finland, Iceland and Ashkenazim. The original document contains color images.