What role does genetic predisposition play in the development of prostate cancer? Genetic predisposition plays a significant role in prostate cancer. Several genetic mutations are associated with the development of prostate cancer, but not all men who have a family history (case in the family) of the disease have a detectable mutation for the disease. The science of genetic mutations and their role in the development of cancer is in its infancy, and it is likely that there are a number of gene mutations associated with prostate cancer that have yet to be discovered. It is also possible that this condition results from a combination of genetic factors that increase the risk in some men. Therefore, even if a man does not have a known genetic mutation responsible for developing prostate cancer, he should consult his doctor if he has a family history of the condition. What role does the presence of a case of the disease in the family play in the development of prostate cancer? Men who have a father, brother or son who has prostate cancer have a higher risk of developing the disease. The risk is greater if a male relative had prostate cancer at an early age or if many men in the family are affected by the disease. It can be difficult to separate genetic factors from environmental factors as a cause of prostate cancer. Overall, about 20% of prostate cancer cases are thought to be “familial” and this may be due to a combination of shared genes and shared lifestyles. Men who have a family history (case in the family) of breast cancer in women in their lineage also have an increased risk of developing prostate cancer. Which genetic mutations and syndromes are associated with prostate cancer? It is estimated that 10% of prostate cancer cases are linked to inherited mutations for which there are now tests. The risk of prostate cancer being hereditary increases if at least three of the patient’s relatives have had prostate cancer. Some genetic mutations associated with prostate cancer include: BRCA gene mutations – both BRCA1 gene mutations and BRCA2 gene mutations carry an increased risk of prostate cancer. It is important to note that both types of mutations can be associated with different types of cancer in different family members. For example, there is greater concern in men who have one of these mutations and relatives who had breast cancer or pancreatic cancer at a young age than if the patient had several male relatives who had prostate cancer at a later age; Lynch syndrome (hereditary nonpolyposis colorectal cancer) – caused by mutations in DNA mismatch repair genes and is more strongly associated with colorectal cancer. RNASEL mutations – these mutations affect a tumor suppressor gene; HOXB13 mutations – these mutations are uncommon and are associated with prostate cancer in younger men Usually, it is not the genetic mutation itself that causes the cancer.Many of the genes associated with increased cancer risk are tumor suppressor genes. Tumor suppressor genes, such as the BRCA genes, code for proteins that work to repair damaged DNA or eliminate damaged cells from the body. When these proteins are abnormal, they cannot do their job properly. Instead of being eliminated, a cell can progress and become a cancer cell. Humans have two copies of each tumor suppressor gene, one inherited from each parent. Because both copies must usually be mutated for cancer to develop, not every man who inherits either of these mutations will develop cancer. Instead, these patients have a “genetic predisposition” to cancer. There are other types of genes, oncogenes, where only one copy needs to be mutated for cancer to develop, but this is much less common in prostate cancer. Bibliography: American Cancer Society. Prostate Cancer Risk Factors American Cancer Society. How family history affects prostate cancer risk Krstev S, Knutsson A. Occupational risk factors for prostate cancer: a meta-analysis Verywell Health. Causes and Risk Factors of Prostate Cancer