ProstateDx ClearTM is a multi-gene test that analyzes 16 prostate cancer susceptibility genes.
What is hereditary prostate cancer?
Cancer development is a complex process. If certain genes are mutated and do not give cells proper instructions about when to grow and divide, then cancer could develop. Environmental factors, such as UV light, tobacco and diet can increase mutation rates. Some of these mutations will be repaired, but some mutations will not. These mutations will be present in some cells in the body and this will increase the risk of cancer development.
However in families with hereditary forms of cancer, a mutation is present in a very important gene and is present in all cells in the body. Inheriting a cancer-causing mutation in one of the cancer-associated genes does not mean that cancer will definitely occur. It means only that your risk is higher than for someone who does not carry such a mutation in their cells.
Prostate cancer is the second most common cancer among men in the United States. According to the National Institute of Health, about 1 in 7 men will be diagnosed with prostate cancer at some point in their life, with more than 60% of men diagnosed after age 65. African American men have a higher risk of developing prostate cancer than white males do. Approximately 10% of prostate cancers are hereditary. The same mutations in cancer predisposing genes that increase the risk of breast and ovarian cancer in women, also increase the chance of prostate cancer and male breast cancer in men. And fathers are just as likely to pass the risk for breast and ovarian cancer to their daughters, as are their mothers. Men carrying a pathogenic mutation in the BRCA1 or BRCA2 gene have an increased risk of prostate cancer, pancreatic cancer, and male breast cancer (Table 1).
What is hereditary prostate cancer?You could have an inherited risk if:
- 3 or more first-degree relatives diagnosed with prostate cancer at any age
- Prostate cancer seen in 3 generations on the same side of the family
- 2 or more close family members (i.e brother, father, grandfather) on the same side of the family diagnosed with prostate cancer before 55.
What is ProstateDx ClearTM?ProstateDx ClearTM is a multi-gene test that analyses point mutations, gross deletions and duplications in the following genes associated with inherited prostate, breast, colorectal and some other types of cancer: ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, MLH1, MRE11A, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, RAD51D and TP53. We use next-generation sequencing (NGS) technology to identify variants in the coding regions of these genes. The identified variants are classified according to the guidelines for sequence variant interpretation of the American College of Medical Genetics and Genomics (ACMG). Variant classification categories include pathogenic, likely pathogenic, variant of unknown significance (VUS), likely benign, and benign.
- Pathogenic variants - Genetic changes with known clinical significance that is associated with an increased risk of hereditary cancer.
- Likely pathogenic variants – Genetic changes that have some preliminary clinical data indicating an association with hereditary cancer but not sufficient to make a definitive determination of pathogenicity.
- Variants of uncertain significance (VUS) – Genetic changes with either conflicting or no supporting data to determine their pathogenicity.
- Negative Result – No variant of clinical or uncertain significance was detected. Negative result does not eliminate the risk of developing cancer.
Benign variants that have sufficient evidence to be considered of no clinical significance and likely benign variants that are not likely to increase the risk of cancer will not be shown on the report.
What are the possible benefits of ProstateDx Clear testing?Any hereditary cancer susceptibility testing reduces the uncertainty about the risks of cancer for people and their families. Such testing may be able to explain the cancer history in your family. If a cancer predisposing mutation is identified, it can help your doctor to guide your medical care and decrease the risk of prostate and other associated cancers.
ProstateDx ClearTM genes, Associated Cancers and CharacteristicsProstateDx ClearTM is a multi-gene test that analyzes 16 prostate cancer susceptibility genes ( listed below ). Although all males (especially after age 50) have some risk of developing prostate cancer at some point in their lives, having a mutation in one of the prostate cancer susceptibility genes increases this risk. Men who have a mutation in one of the prostate cancer susceptibility genes also have an increased risk of pancreatic, gastric, male breast and other cancer types.
|Click on any gene to view its definition|
The BRCA1 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA1 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA1 protein plays a critical role in maintaining the stability of a cell's genetic information.
Research suggests that the BRCA1 protein also regulates the activity of other genes and plays an essential role in embryonic development. To carry out these functions, the BRCA1 protein interacts with many other proteins, including other tumor suppressors and proteins that regulate cell division.
The BRCA2 protein is involved in repairing damaged DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several other proteins to mend breaks in DNA. These breaks can be caused by natural and medical radiation or other environmental exposures, and they also occur when chromosomes exchange genetic material in preparation for cell division. By helping to repair DNA, the BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic information.
Researchers suspect that the BRCA2 protein has additional functions within cells. For example, the protein may help regulate cytokinesis, which is the step in cell division when the fluid surrounding the nucleus (the cytoplasm) divides to form two separate cells. Researchers are investigating the protein's other potential activities.
The CHK2 protein is activated when DNA becomes damaged or when DNA strands break. DNA can be damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material.
In response to DNA damage, the CHK2 protein interacts with several other proteins, including tumor protein 53 (which is produced from the TP53 gene). These proteins halt cell division and determine whether a cell will repair the damage or self-destruct in a controlled manner (undergo apoptosis). This process keeps cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.
Nibrin interacts with two other proteins, produced from the MRE11A and RAD50 genes, as part of a larger protein complex. Nibrin regulates the activity of this complex by carrying the MRE11A and RAD50 proteins into the cell's nucleus and guiding them to sites of DNA damage. The proteins work together to mend broken strands of DNA. DNA can be damaged by agents such as toxic chemicals or radiation, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division. Repairing DNA prevents cells from accumulating genetic damage that may cause them to die or to divide uncontrollably.
The MRE11A/RAD50/NBN complex interacts with the protein produced from the ATM gene, which plays an essential role in recognizing broken strands of DNA and coordinating their repair. The MRE11A/RAD50/NBN complex helps maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division. Because these functions are critical for preventing the formation of cancerous tumors, nibrin is described as a tumor suppressor.
The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors.
Because p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the "guardian of the genome."