Prostate cancer genes

Prostate cancer, also known as carcinoma of the prostate, is the development of cancer in the prostate, a gland in the male reproductive system.[1] Most prostate cancers are slow growing; however, some grow relatively quickly.[2][3]The cancer cells may spread from the prostate to other parts of the body, particularly the bones and lymph nodes.[4] It may initially cause no symptoms.[3] In later stages it can lead to difficulty urinating, blood in the urine, or pain in the pelvis, back or when urinating.[5] A disease known as benign prostatic hyperplasia may produce similar symptoms. Other late symptoms may include feeling tired due to low levels of red blood cells.[3]

Factors that increase the risk of prostate cancer include: older age, a family history of the disease, and race. About 99% of cases occur in those over the age of 50. Having a first-degree relative with the disease increases the risk two to threefold. In the United States it is more common in the African American population than the white Americanpopulation. Other factors that may be involved include a diet high in processed meat, red meat, or milk products or low in certain vegetables.[2] An association with gonorrhea has been found, but a reason for this relationship has not been identified.[6] Prostate cancer is diagnosed by biopsy. Medical imaging may then be done to determine if the cancer has spread to other parts of the body.[5]

Prostate cancer screening is controversial.[2][3] Prostate-specific antigen (PSA) testing increases cancer detection but does not decrease mortality.[7] The United States Preventive Services Task Force recommends against screening using the PSA test, due to the risk of overdiagnosis and overtreatment, as most cancer diagnosed would remain asymptomatic. The USPSTF concludes that the potential benefits of testing do not outweigh the expected harms.[8]While 5α-reductase inhibitors appear to decrease low-grade cancer risk they do not affect high-grade cancer risk and thus are not recommended for prevention.[2] Supplementation with vitamins or minerals does not appear to affect the risk.

A BRCA mutation is a mutation in either of the BRCA1 and BRCA2 genes, which are tumor suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Harmful mutations in these genes may produce a hereditary breast-ovarian cancer syndrome in affected persons. Only 5-10% of breast cancer cases in women are attributed to BRCA1 and BRCA2 mutations (with BRCA1mutations being slightly more common than BRCA2 mutations), but the impact on women with the gene mutation is more profound.[1] Women with harmful mutations in either BRCA1 or BRCA2 have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal.[2] The risk of breast and ovarian cancer is higher for women with a high-risk BRCA1 mutation than with a BRCA2 mutation. Having a high-risk mutation does not guarantee that the woman will develop any type of cancer, or imply that any cancer that appears was actually caused by the mutation, rather than some other factor.

High-risk mutations, which disable an important error-free DNA repair process (homology directed repair), significantly increase the person’s risk of developing breast cancer, ovarian cancer and certain other cancers. Why BRCA1 and BRCA2 mutations lead preferentially to cancers of the breast and ovary is not known, but lack of BRCA1 function seems to lead to non-functionalX-chromosome inactivation. Not all mutations are high-risk; some appear to be harmless variations. The cancer risk associated with any given mutation varies significantly and depends on the exact type and location of the mutation and possibly other individual factors.

Mutations can be inherited from either parent and may be passed on to both sons and daughters. Each child of a genetic carrier, regardless of sex, has a 50% chance of inheriting the mutated gene from the parent who carries the mutation. As a result, half of the people with BRCA gene mutations are male, who would then pass the mutation on to 50% of their offspring, male or female. The risk of BRCA-related breast cancers for men with the mutation is higher than for other men, but still low.[3] However, BRCA mutations can increase the risk of other cancers, such as colon cancer, pancreatic cancer, and prostate cancer.

Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels ofbreast cancer and ovarian cancer in genetically related families (either one individual had both, or several individuals in thepedigree had one or the other disease). The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family.[1]

Hereditary causes

 Approximate proportion of hereditary breast cancer cases caused by each gene
  BRCA1 mutations (28%)
  BRCA2 mutations (19%)
  All other known genes (8%)
  Unknown genes or multiple genes (45%)

A number of genes are associated with HBOC.[2] The most common of the known causes of HBOC are:

  • BRCA mutations:[2] Harmful mutations in the BRCA1 and BRCA2 genes can produce very high rates of breast and ovarian cancer, as well as increased rates of other cancers.

Other identified genes include:

  • TP53: Mutations cause Li-Fraumeni syndrome. It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene.[2]
  • PTEN: Mutations cause Cowden syndrome, which produces hamartomas (benign polyps) in the colon, skin growths, and otherclinical signs, as well as an increased risk for many cancers.[2]
  • CDH1: Mutations are associated with lobular breast cancer and gastric cancer.[2]
  • STK11: Mutations produce Peutz–Jeghers syndrome. It is extremely rare, and creates a predisposition to breast cancer, intestinal cancer, and pancreatic cancer.[2]
  • CHEK2: Approximately one out of 40 northern Europeans have a mutation in this gene, making it a common mutation. Considered a moderate-risk mutation, it may double or triple the carrier’s lifetime risk of breast cancer, and also increase the risk of colon cancer and prostate cancer.[2]
  • ATM: Mutations cause ataxia telangectasia; female carriers have approximately double the normal risk of developing breast cancer.[2]
  • PALB2: Studies vary in their estimate of the risk from mutations in this gene. It may be moderate risk, or as high as BRCA2
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  • Connie’s comments: Cancer/toxins reside in fat tissues and the same cancer that can attack breasts and ovaries can also attack the prostate.