The prostate, a part of the male reproductive system, is made up of a number of cell types that work together to perform a range of actions that support male reproductive function. Prostate cancer develops when any of the cell types within the prostate mutate and begin to divide out of control, leading to the formation of a tumor. The National Cancer Institute reports that prostate cancer accounted for 192,280 new cancer diagnoses and 27,360 deaths in the United States in 2009. Prostate cancer development can be governed by genetics, especially in patients with a family history of the disease. A number of genes have been linked to an increased risk of developing prostate cancer.
BRCA1/2
Two genes thought to be associated with a predisposition for prostate cancer are BRCA1 and BRCA2. Both BRCA 1 and 2 are called tumor suppressor genes, and they function to prevent the genetic mutations that drive the development of cancer. Under normal conditions, BRCA1/2 play a role in halting cell proliferation when the cell's DNA becomes damaged, to allow the cell to fix mistakes in the DNA before it continues to divide. If BRCA1/2 function is lost, the cell continues to divide and accumulate genetic mutations, eventually leading to cancer
Genetic mutation to either the BRCA1 or BRCA2 genes increases the risk of developing prostate cancer. The National Cancer Institute reports that mutation to BRCA1 can increase the risk of prostate cancer in men over 65 years old, while certain mutations to BRCA2 increases the risk of prostate cancer in younger men. Genetic testing to check for mutations to either gene is available, and recommended for men with a family history of prostate cancer. Since BRCA1/2 are also associated with breast cancer, men with a family history of breast cancer, especially male breast cancer, should also undergo genetic testing.
HPCX
The locus HPCX is also associated with an increased risk of prostate cancer. HPCX stands for hereditary prostate cancer X, and it is a region of DNA that contains five genes called SPANX genes, which contribute to sperm production. The locus also contains another gene called LDOC1, which is turned off in some prostate cancers. Variations within HPCX are linked to susceptibility to prostate cancer.
A study published in "Genome Research" in 2005 by Dr. N. Kouprina found that a number of DNA variations that slightly change the DNA, called recombinations, changed the structure of the genes within the HPCX region. Dr. Kouprina speculates that the architecture of the HPCX locus helps determine an individual's risk of developing prostate cancer, with certain arrangements of genes leading to prostate cancer susceptibility.
Perlecan
Another gene thought to play a role in the development of prostate cancer is perlecan, a gene found within a region of DNA that is often mutated in prostate cancer. Perlecan is a protein that functions to regulate signaling within cells. Under normal conditions, perlecan signals for proliferation, and can be turned on or off depending on the needs of the body. In prostate cancer, the cells constantly receive proliferation signals, promoting the development of cancer.
A study published in "Molecular Cancer" in 2006 found that in prostate cancer, perlecan is dysregulated, and it signals for constant cell proliferation. These changes to perlecan activity may be linked to mutations in the perlecan gene itself, or mutations in DNA that regulates perlecan. Further research into the dysregulation of perlecan in prostate cancer may lead to the development of new genetic testing for prostate cancer.
References
- National Cancer Institute: Prostate Cancer
- National Cancer Institute: Prostate Cancer Susceptibility Loci
- "Genome Research"; Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27; Dr. Natalay Kouprina et al; 2005
- "Molecular Cancer"; Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway; M.W. Datta et al; March 2006
