The Genetics of Prostate Cancer

What are genes?

Genes are small individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in prostate cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

A person may either be born with a genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Most prostate cancer (about 75%) is considered sporadic, meaning that the damage to the genes occurs by chance after a person is born. Familial (runs in the family) prostate cancer is less common (about 20%) and occurs because of a combination of shared genes and shared environmental or lifestyle factors. Hereditary (inherited) prostate cancer is rare (about 5%) and occurs when gene mutations are passed within a family, from one generation to the next.

What are the chances a mutated gene is inherited?

Every cell usually has two copies of each gene: one inherited from a person’s mother and one inherited from a person’s father. Hereditary prostate cancer appears to follow an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a gene mutation also has a 50% chance of having the same mutation.

What is a man's average risk for prostate cancer?

A man with an average risk for prostate cancer has about a 14% chance of developing prostate cancer by age 80. The risk of prostate cancer is slightly higher for black men than for white men.

How common is prostate cancer?

Prostate cancer is the most common cancer and the second most common cause of cancer death for men. In 2009, an estimated 192,280 men in the United States will be diagnosed with prostate cancer. It is estimated that 27,360 deaths from this disease will occur this year. Although the number of deaths from prostate cancer is declining among all men, the death rate remains more than twice as high for black men than for white men.

How can a man know if he has inherited a genetic mutation that increases his risk of prostate cancer?

Only genetic testing can determine whether a man has a genetic mutation, but there are no genetic tests available to specifically determine a man's chance of developing prostate cancer. Currently, there is not one gene that definitively causes prostate cancer, although some genes or gene mutations have been shown to be more common for men with prostate cancer. Research to identify genes associated with an increased risk of prostate cancer is ongoing, and men with a strong family history of prostate cancer may be eligible to participate in such studies.

For more information, read about Genetic Testing and Clinical Trials.

How does a man know if prostate cancer runs in his family?

A man may have an increased risk of developing prostate cancer if two or more close relatives have prostate cancer. Familial prostate cancer is when two or more first-degree relatives (father, brother, son) are diagnosed with prostate cancer. Hereditary prostate cancer is when a family has any of the following characteristics:

Three or more first-degree relatives with prostate cancer
or

Prostate cancer in three generations on the same side of the family
or

Two or more close relatives (father, brother, son, grandfather, uncle, nephew) on the same side of the family diagnosed with prostate cancer younger than age 55
Not all doctors agree with the same definitions for familial prostate cancer and hereditary prostate cancer, but the terms are used to help researchers and doctors learn more about these groups of patients and their family histories. Having a family history of prostate cancer does not necessarily mean that a man will develop prostate cancer.

What is a man's risk if prostate cancer runs in his family?

If a man has a first-degree relative with prostate cancer, his risk of developing prostate cancer is two to three times greater than the average risk. The risk increases as more relatives are diagnosed with prostate cancer. Researchers have made progress in understanding how certain changes in the DNA of cancer cells can cause normal prostate cells to become cancerous, and this information may help doctors understand how prostate cancer can run in families.

Most experts strongly recommend that people concerned about a family history of prostate cancer first consult a genetic counselor. Genetic counselors are trained to determine the possibility of hereditary cancer risk for a family and can identify appropriate genetic testing or research studies.

Which inherited genetic mutations raise the risk of prostate cancer?

Researchers continue to find genes that may be associated with an increased risk of prostate cancer. However, more research is needed to better understand these genes before genetic testing can be used to determine a man’s risk of developing prostate cancer.

One gene known to increase the risk of prostate cancer, by as much as three times the average risk, is located on chromosome 17. The normal function of this gene is not known, but men who inherit a mutated version of the gene have a 44% higher level of the prostate-specific antigen (PSA) protein, a protein in the blood used to help diagnose prostate cancer. However, not everyone with this gene will develop prostate cancer.

Other genes that may cause an increased risk of developing prostate cancer, include HPC1, HPC2, HPCX, and CAPB. Research on these genes is still new and genetic tests are not yet available for routine screening because it is not clear that they definitely cause prostate cancer.

Are there other genetic conditions associated with an increased risk of prostate cancer?

Men with BRCA1 and BRCA2 (BRCA stands for BReast CAncer) gene mutations have an increased risk of prostate cancer. BRCA1 and BRCA2 gene mutations are most commonly associated with hereditary breast and ovarian cancer (HBOC) syndrome. Men with BRCA1 mutations have a slightly increased risk, while men with BRCA2 mutations have about a 20% risk of developing prostate cancer during their life, usually before age 65. For this reason, men with BRCA1 or BRCA2 gene mutations are encouraged to begin annual prostate cancer screening at age 40. Men with BRCA1 or BRCA2 gene mutations also have an increased risk of breast cancer.

BRCA1 and BRCA2 are tumor suppressor genes. A tumor suppressor gene makes proteins that prevent tumor formation by limiting cell growth. Mutations in a tumor suppressor gene causes a loss of the ability to restrict tumor growth and, as a result, cancer can develop. Genetic testing for the BRCA1 and BRCA2 genes is available. However, mutations in BRCA1 and BRCA2 are thought to be responsible for only a small percentage of familial prostate cancer cases. Genetic testing may only be appropriate for families with prostate cancer that may also have HBOC.

For more information, read the Cancer.Net Guide to Hereditary Breast and Ovarian Cancer.

What is a man's risk level?

In addition to family history, other environmental and lifestyle factors may influence the risk of prostate cancer. Discussing family history and personal risk factors with a doctor can help a man better understand his risk. If a man has a higher than average risk, he may consider genetic counseling and early detection screening.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to prostate cancer cannot predict that a man will develop cancer. Controllable risk factors, such as eating a balanced, heart-healthy diet (a diet low in saturated fat, cholesterol, and sodium), maintaining a healthy weight, exercising, limiting alcoholic beverages, and avoiding tobacco products also play a role. Research to better understand the link between genetic mutations and prostate cancer is ongoing. Talk with a doctor for more information about risk factors, prevention, and screening for prostate cancer