What Causes Prostate Cancer?

Researchers do not know exactly what causes prostate cancer. But they have found some risk factors and are trying to learn just how these factors might cause prostate cells to become cancer cells.

On a basic level, prostate cancer is caused by changes in the DNA of a normal prostate cell. 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 DNA affects more than just how we look.

Some genes control when our cells grow, divide into new cells, and die:

• Certain genes that help cells grow, divide, and stay alive are called oncogenes.
• Genes that normally keep cell growth under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancer can be caused by DNA mutations (or other types of changes) that keep oncogenes turned on, or that turn off tumor suppressor genes. These types of gene changes can lead to cells growing out of control.

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

Inherited gene mutations

Some gene mutations can be passed from generation to generation (inherited) and are found in all cells in the body. Inherited gene changes are thought to play a role in about 10% of prostate cancers. Cancer caused by inherited genes is called hereditary cancer. Several inherited mutated genes have been linked to hereditary prostate cancer, including:

• BRCA1 and BRCA2: These tumor suppressor 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 these genes more commonly cause breast and ovarian cancer in women. But changes in these genes (especially BRCA2) also account for a small number of prostate cancers.
• CHEK2, ATM, PALB2, and RAD51D: 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 be made 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. Fortunately, this mutation is rare.

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

Acquired gene mutations

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

Every time a cell prepares to divide into 2 new cells, it must copy its DNA. 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 may make prostate cancer more likely.

For example, androgens (male hormones), such as testosterone, promote prostate cell growth. Having higher levels of androgens might contribute to prostate cancer risk in some men.

Some research has found that men with high levels of another hormone, insulin-like growth factor-1 (IGF-1), are 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.