What Causes Prostate Cancer?

Researchers have found some risk factors for prostate cancer, although it’s not yet clear exactly how these factors might increase prostate cancer risk. On a basic level, prostate cancer is caused by changes in the DNA of a normal prostate cell.

Gene changes that might lead to prostate cancer

DNA is the chemical in our cells that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA. But our genes affect more than just how we look.

Some genes normally help control when our cells grow, divide to make new cells, or repair mistakes in DNA, or they cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control. For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

DNA changes can either be inherited from a parent, or they can be acquired during a person’s lifetime.

Inherited gene mutations

Some gene mutations can be passed on in families and are found in all of a person’s cells. Such inherited gene changes are thought to be a major factor in up to 10% of prostate cancers. Cancer caused by inherited genes is called hereditary cancer.

Inherited mutations in several genes have been linked to hereditary prostate cancer, including:

• BRCA1 and BRCA2: These genes normally help repair mistakes in a cell’s DNA (or cause the cell to die if the mistake can’t be fixed). Inherited mutations in either of these genes greatly increase the risk of breast and ovarian cancer in women. They are also linked to some other cancers. For example, changes in these genes (especially BRCA2) are linked to an increased risk of prostate cancer.
• CHEK2, ATM, PALB2, and RAD51: Mutations in these other DNA repair genes might also be responsible for some hereditary prostate cancers.
• DNA mismatch repair genes (such as MSH2, MSH6, MLH1, and PMS2): These genes normally help fix mistakes (mismatches) in DNA that can happen when a cell is preparing to divide into 2 new cells. (Cells must make a new copy of their DNA each time they divide.) Men with inherited mutations in one of these genes have a condition known as Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), and are at increased risk of colorectal, prostate, and some other cancers.
• RNASEL (formerly HPC1): The normal function of this tumor suppressor gene is to help cells die when something goes wrong inside them. Inherited mutations in this gene might let abnormal cells live longer than they should, which can lead to an increased risk of prostate cancer.
• HOXB13: This gene is important in the development of the prostate gland. Mutations in this gene have been linked to early-onset prostate cancer (prostate cancer diagnosed at a young age) that runs in some families. This mutation is rare.

Other inherited gene mutations may account for some hereditary prostate cancers, and research is being done to find these genes.

If you have prostate cancer, testing the cancer cells for these types of gene changes might be important, for a couple of reasons:

• The results of testing might affect your treatment options. Some medicines used to treat prostate cancer (such as certain targeted drugs) are only likely to be helpful if your cancer cells have one of these gene changes.
• If testing finds a gene change, your doctor might suggest genetic counseling and testing. If the tumor cells have a gene mutation, testing some of your other cells (such as from a blood sample) for the same mutation can show if you inherited it (and therefore if it’s in all of your cells). This might help you learn more about your risk of other cancers, and possibly the risks among other members of your family. To learn more, see Genetic Counseling and Testing for Prostate Cancer Risk.

Acquired gene mutations

Some genes can change during a person’s lifetime. This type of mutation is not passed on to children, and it’s found only in cells that come from the original mutated cell. These are called acquired mutations. Most gene mutations linked to prostate cancer develop during a man’s life, rather than having been inherited.

Every time a cell prepares to divide into 2 cells, it needs to make a copy of its DNA for the new cell. This process isn’t perfect, and sometimes errors occur, leaving defective DNA in the new cell. It’s not clear how often these DNA changes might be random events, and how often they are influenced by other factors (such as diet, hormone levels, etc.).

In general, the more quickly prostate cells grow and divide, the more chances there are for mutations to occur. Therefore, anything that speeds up this process might make prostate cancer more likely.

For example, androgens (male hormones), such as testosterone, can promote prostate cell growth. Having higher levels of androgens might contribute to prostate cancer risk in some men, although studies so far have not found a consistent link.

Some research has found that men with high levels of another hormone, insulin-like growth factor-1 (IGF-1), might be more likely to get prostate cancer. However, other studies have not found such a link. Further research is needed to make sense of these findings.

As mentioned in Prostate Cancer Risk Factors, some studies have found that inflammation in the prostate might be linked to prostate cancer. One theory is that inflammation might lead to cell DNA damage, which could contribute to a normal cell becoming a cancer cell. More research is needed in this area.

Exposure to radiation or cancer-causing chemicals can cause DNA mutations in many organs, but so far these factors haven’t been shown to be important causes of mutations in prostate cells.