Question: What are the genetic changes related to prostate cancer ?
Answer: Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In most cases of prostate cancer, these genetic changes are acquired during a man's lifetime and are present only in certain cells in the prostate. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in prostate cancer cells. Less commonly, genetic changes present in essentially all of the body's cells increase the risk of developing prostate cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop prostate cancer. Inherited mutations in particular genes, such as BRCA1, BRCA2, and HOXB13, account for some cases of hereditary prostate cancer. Men with mutations in these genes have a high risk of developing prostate cancer and, in some cases, other cancers during their lifetimes. In addition, men with BRCA2 or HOXB13 gene mutations may have a higher risk of developing life-threatening forms of prostate cancer. The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. For this reason, the BRCA1 and BRCA2 proteins are considered to be tumor suppressors, which means that they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair the cell's ability to fix damaged DNA, allowing potentially damaging mutations to persist. As these defects accumulate, they can trigger cells to grow and divide uncontrollably and form a tumor. The HOXB13 gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the protein produced from the HOXB13 gene is called a transcription factor. Like BRCA1 and BRCA2, the HOXB13 protein is thought to act as a tumor suppressor. HOXB13 gene mutations may result in impairment of the protein's tumor suppressor function, resulting in the uncontrolled cell growth and division that can lead to prostate cancer. Inherited variations in dozens of other genes have been studied as possible risk factors for prostate cancer. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1, BRCA2, or HOXB13 genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence of variations in many of these genes may significantly impact a person's risk of developing this form of cancer. In many families, the genetic changes associated with hereditary prostate cancer are unknown. Identifying additional genetic risk factors for prostate cancer is an active area of medical research. In addition to genetic changes, researchers have identified many personal and environmental factors that may contribute to a person's risk of developing prostate cancer. These factors include a high-fat diet that includes an excess of meat and dairy and not enough vegetables, a largely inactive (sedentary) lifestyle, obesity, excessive alcohol use, or exposure to certain toxic chemicals. A history of prostate cancer in closely related family members is also an important risk factor, particularly if the cancer occurred at an early age.