Question: What are the genetic changes related to breast cancer ?
Answer: 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. In most cases of breast cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the breast. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in breast cancer cells. Less commonly, gene mutations present in essentially all of the body's cells increase the risk of developing breast 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 breast cancer. Some breast cancers that cluster in families are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. These genes are described as "high penetrance" because they are associated with a high risk of developing breast cancer, ovarian cancer, and several other types of cancer in women who have mutations. Men with mutations in these genes also have an increased risk of developing several forms of cancer, including breast 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. They are described as tumor suppressors because they help keep cells from growing and dividing too fast or in an uncontrolled way. 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 breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene; hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes 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 breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors. Mutations in dozens of other genes have been studied as possible risk factors for breast 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 breast 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 breast cancer. In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast 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 person's risk of developing breast cancer. These factors include gender, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood.