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 much of how a cell functions, including its rate of growth, how often it divides, when it should live, and when it should die. Genes control these functions by producing proteins that carry out specific tasks for the cell. These proteins act as messengers in 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?

Scientists now know that the cancer process probably begins because one or more genes in a cell are mutated (damaged or missing). This means that they either code for an abnormal protein or no protein at all. The net result is that the cascade of information flow in the cell is disrupted.

Genetic mutations can occur at two distinct time points: either a person is born with the genetic mutation in all of their cells (germline mutation) or a person acquires an alteration in a single cell during his or her lifetime which is then passed on to all cells that are descended from that single cell (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. Hereditary prostate cancer (about 5%) occurs when gene mutations are passed from generation to generation. Familial prostate cancer (about 20%) occurs due to a combination of shared genes and shared environmental or lifestyle factors.

What are the chances a mutated gene is inherited?

Normally, every cell has two copies of each gene: one inherited from the mother and one inherited from the father. Hereditary prostate cancer appears to follow an autosomal dominant inheritance pattern. In autosomal dominant inheritance a mutation happens in only one copy of the gene. This means that a parent with a mutation may pass on a copy of their working gene or a copy of their altered gene. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation.

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

A man at 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 in black men than in white men.

How common is prostate cancer?

Prostate cancer is the most common cancer among men. In 2008, approximately 186,320 men in the United States will be found to have prostate cancer. Prostate cancer is the second leading cause of cancer death in men, and an estimated 28,660 deaths are expected to occur in the United States in 2008. Although the number of deaths from prostate cancer is declining among all men, the death rate remains more than twice as high in black men than in 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 person has a genetic mutation. There are currently no genetic tests available to specifically determine someone's chances of developing prostate cancer. People with a strong family history of prostate cancer may be eligible to participate in research studies designed to identify genes associated with an increased risk of prostate cancer.

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

Having two or more close relatives with prostate cancer may increase a man's risk of prostate cancer. When two or more first-degree relatives (father, brother, son) are diagnosed with prostate cancer, it may be called familial prostate cancer. It is called hereditary prostate cancer if any of the definitions below apply to a family:

• 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

While not all doctors agree with the same definitions for familial prostate cancer and hereditary prostate cancer, the terms are used to allow researchers and doctors to learn more about these groups of patients and their 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 general population risk. The risk increases as more relatives are diagnosed with prostate cancer. During the last few years, scientists have made great progress in understanding how certain DNA changes can cause normal prostate cells to become cancerous, and this information may help us to understand more clearly how prostate cancer can run in families.

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

Which inherited genetic mutations raise the risk of prostate cancer?

There are a growing number of genes thought to be associated with an increased risk of prostate cancer. However, more research is needed to better understand how these genes impact the risk of prostate cancer before genetic testing becomes available.

Researchers have isolated the first mutant gene known to increase the risk of prostate cancer, perhaps by as much as three times. The gene, the normal function of which is not known, is located on human chromosome 17. Tests have already shown that men who inherit a mutant 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.

Researchers have identified other inherited genes that appear to be responsible for an increased likelihood of developing prostate cancer, including HPC1, HPC2, HPCX, and CAPB. Research on these genes is still preliminary and genetic tests are not yet available; that is, these genes are not ready for use in routine clinical screening tests as it is not yet clear that they are the specific genes responsible for prostate cancer.

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

The risk of prostate cancer is increased in men with BRCA1 and BRCA2 gene mutations, which 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 an estimated lifetime risk approaching 20%. Much of this increased risk applies to men under 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. Tumor suppressor genes make proteins that suppress tumor formation by limiting cell growth. Mutations in tumor suppressor genes result in 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 also have a history suggesting HBOC.

What is a person's risk level?

In addition to family history, there are other environmental and lifestyle factors that 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 person has a higher than average risk, he may benefit from genetic counseling and early detection strategies.

A risk factor is anything that increases a person's risk of developing a disease. Having a particular genetic mutation linked to prostate cancer does not yet accurately predict that a person will develop cancer. Research is underway to clarify these risks. Controllable risk factors include eating a balanced diet, maintaining a healthy weight, exercising, limiting alcoholic beverages, and avoiding tobacco products. Research continues to better understand the link between genetic mutations and prostate cancer. Consult a doctor for more information.

Additional Resources

Guide to Prostate Cancer