Prostate cancer

Prostate cancer begins when cells in the prostate gland start to grow out of control. The prostate is a gland found only in men, just below the bladder and in front of the rectum. Its function is to produce some of the fluid that forms part of semen.

The size of the prostate can change as a man ages. In young men, it is about the size of a walnut, but it can be much larger in older men.

In terms of the incidence of prostate cancer, statistics indicate that 1 in 8 men may develop prostate cancer at some point in their lives. This absolute risk should be taken as a starting point, as individual risk may be higher or lower, depending on uncontrollable factors such as age (most cases are detected in men over 50), race (the risk in men of African descent is higher) and family history. It also depends on controllable factors such as weight and diet.

Prostate cancer is always caused by a genetic abnormality (a “mistake” in the genetic material). Most of the time, 85-90% of the time, these genetic abnormalities occur sporadically, as a result of the natural ageing process. However, the remaining 5-10% are due to a genetic abnormality inherited from the father or mother.

There is no sure way to prevent prostate cancer. Many risk factors, such as age, race and family history, cannot be controlled. But there are some things you can do to reduce your risk of prostate cancer.

Along with a healthy lifestyle (proper weight, balanced diet, and exercise), screening (PSA testing) is an essential tool for the prevention and early detection of prostate cancer. When prostate cancer is detected at an early stage, there is a good chance of recovery.

In the case of a family history, it may also be advisable to perform a genetic test to determine whether there is an increased risk. In case of a positive result, this will help to determine further preventive strategies to be taken.

Approximately 10% of prostate cancers have an inherited cause. Genes associated with hereditary prostate cancer include:

• BRCA1 and BRCA2: these tumour suppressor genes normally help repair errors in a cell’s DNA (or cause the cell to die if the error cannot be repaired). Inherited mutations in these genes most commonly cause breast and ovarian cancer in women. But changes in these genes (especially BRCA2) are also responsible for prostate cancers.
• CHEK2, ATM, PALB2 and RAD51D: Mutations in these other DNA repair genes may also be responsible for some hereditary prostate cancers.
• DNA error repair genes (such as MSH2, MSH6, MLH1 and PMS2): these genes normally help repair DNA errors that can occur during DNA replication. People with inherited mutations in one of these genes may have Lynch syndrome (also known as hereditary non-polyposis colorectal cancer) and have an increased risk of colorectal, prostate and other cancers.
• RNASEL (formerly HPC1): the normal function of this tumour suppressor gene is to help cells die when something goes wrong inside them. Inherited mutations in this gene can allow abnormal cells to 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 prostate cancer diagnosed at an early age that runs in some families. 

In most cases, the results obtained from the analysis of these genes allow for detailed and informative genetic counselling and a specific recommendation on clinical procedure.

When family history suggests the presence of a heritable mutation, or if a close relative has a mutation in one of the risk genes, predictive genetic testing can be offered.

Genetic testing for prostate cancer is indicated in patients with a family history suggestive of a familial mutation.

Positive result matching the mutation found in the family

If you have tested positive and have been found to have the known familial mutation that is or was responsible for the development of prostate cancer in your family, then you have a significantly higher risk of developing the disease in your lifetime than the rest of the population. It does not imply that you have or will develop the disease, but it does imply that you should intensify surveillance and follow preventive guidelines. In addition, there may be an increased risk of cancer for their offspring.

Positive result in a family in which the causal mutation is not known to exist

In the case of a positive result in a patient for whom no family member with the disease has been or can be tested, it can be assumed that the same mutation also caused the disease in family members who developed prostate cancer. In other words, this person also has a higher risk of developing cancer.

Negative result in a family with known causal mutation

If you have a negative result, this means that the known familial mutation responsible for the development of prostate cancer in the family is not detected in the patient or that there may be a mutation in a gene that has not yet been associated with prostate cancer. This means that you do not have an increased risk of developing prostate cancer. Therefore, you have the same risk as the general population (approximately 4%) of developing prostate cancer in your lifetime.

Negative result in a family with no known causal mutation

If no known mutation has been found in any family member despite there being some people affected by prostate cancer, it may be that another gene is responsible for the development of the cancer and/or that the cancers in your family are not due to an inherited predisposition.

Finally, the result of the genetic test may indicate the presence of a genetic variant that doctors do not have enough information about to be able to assess correctly (variant of uncertain (unknown) significance, VUS). In these situations, the benefit to the patient cannot always be defined.

In order to decide whether a genetic study is advisable, it is ideally important to compile a family tree over 3 generations. By analysing this tree, it can be determined whether there is an increased risk of prostate cancer and a genetic test can be recommended. As a general rule, it is recommended if at least one of the following criteria is met:

• 3 or more first-degree relatives with prostate cancer.
• 2 or more first-degree relatives in the same part of the family diagnosed with prostate cancer before the age of 55.
• Prostate cancer in 3 generations on the same side of the family (paternal or maternal).

If you have or have already had prostate cancer, it is advisable to undergo the study when:

• You have or have had prostate cancer before the age of 50.
• Other members of your family have been diagnosed with breast, ovarian or pancreatic cancer.

The decision about whether or not to have a genetic test to establish the risk of prostate cancer is a personal one and should always be made after genetic counselling. This counselling should try to answer any questions about:

• What it means to do the test
• How the patient may feel while waiting for the results to come back
• What kind of actions can be considered after the results have been obtained

Genetic diagnosis is an essential preventive tool. If a mutation in one of the genes is detected through genetic diagnosis, the risk of developing cancer increases considerably. It is therefore vital that people carrying the mutation undergo different preventive diagnostic methods on a regular basis.

Accurate and regular follow-up is essential to reduce the incidence of cancer and radically reduce the associated mortality.

There are private insurance policies that cover preventive genetic analysis in first-degree relatives of affected persons with a detected familial mutation.
However, there are private insurances that do not cover the costs and are therefore paid by the patient.