What are the genetic changes related to ovarian cancer ?
Cancers occur when a buildup of mutations in critical genesthose that control cell growth and division or repair damaged DNAallow cells to grow and divide uncontrollably to form a tumor. Most cases of ovarian cancer are sporadic; in these cases the associated genetic changes are acquired during a person's lifetime and are present only in certain cells in the ovary. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the TP53 gene occur in almost half of all ovarian cancers. The protein produced from this gene is described as a tumor suppressor because it helps keep cells from growing and dividing too fast or in an uncontrolled way. Most of these mutations change single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, a cancerous tumor may develop. Somatic mutations in many other genes have also been found in ovarian cancer cells.  In hereditary ovarian cancer, the associated genetic changes are passed down within a family. These changes, classified as germline mutations, are present in all the body's cells. In people with germline mutations, other inherited and somatic gene changes, together with environmental and lifestyle factors, also influence whether a woman will develop ovarian cancer.  Germline mutations are involved in more than one-fifth of ovarian cancer cases. Between 65 and 85 percent of these mutations are in the BRCA1 or BRCA2 gene. These gene mutations are described as "high penetrance" because they are associated with a high risk of developing ovarian cancer, breast cancer, and several other types of cancer in women. Compared to a 1.6 percent lifetime risk of developing ovarian cancer for women in the total population, the lifetime risk in women with a BRCA1 gene mutation is 40 to 60 percent, and the lifetime risk in women with a BRCA2 gene mutation is 20 to 35 percent. Men with mutations in these genes also have an increased risk of developing several forms of cancer. The proteins produced from the BRCA1 and BRCA2 genes are tumor suppressors that are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor.  A significantly increased risk of ovarian cancer is also a feature of certain rare genetic syndromes, including a disorder called Lynch syndrome. Lynch syndrome is most often associated with mutations in the MLH1 or MSH2 gene and accounts for between 10 and 15 percent of hereditary ovarian cancers. Other rare genetic syndromes may also be associated with an increased risk of ovarian cancer. The proteins produced from the genes associated with these syndromes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to ovarian cancer, mutations in these genes increase the risk of several other types of cancer in both men and women.  Germline mutations in dozens of other genes have been studied as possible risk factors for ovarian cancer. These genes are described as "low penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall ovarian cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing ovarian cancer.  In many families, the genetic changes associated with hereditary ovarian cancer are unknown. Identifying additional genetic risk factors for ovarian cancer is an active area of medical research.  In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a woman's risk of developing ovarian cancer. These factors include age, ethnic background, and hormonal and reproductive factors. A history of ovarian cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood. + GHR + ovarian cancer