DO WE KNOW WHAT CAUSES PROSTATE CANCER?

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

On a basic level, prostate cancer is caused by changes in the DNA of a prostate cell. Scientists have made great progress in understanding how certain changes in DNA can make normal prostate cells grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes, the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. However, DNA affects more than 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. Others that normally slow down cell division, repair mistakes in DNA, or cause cells to die at the right time are called tumour suppressor genes. Cancer can be caused in part by DNA changes (mutations) that turn on oncogenes or turn off tumour suppressor genes.

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

Inherited DNA mutations

Inherited DNA changes in certain genes seem to cause about 5% to 10% of prostate cancers. Several mutated genes have been linked to a man’s inherited tendency to develop prostate cancer, including:

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 might let abnormal cells live longer than they should, which can lead to an increased risk of prostate cancer.

BRCA1 and BRCA2: These tumour 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 inherited BRCA changes also account for a very small number of prostate cancers.

DNA mismatch repair genes (such as MSH2 and MLH1): These genes normally help fix mistakes (mismatches) in DNA that are 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 these genes have a condition known as Lynch syndrome, and are at increased risk of colorectal, prostate, and some other cancers.

Other inherited gene mutations may account for some cases of hereditary prostate cancer, although none of these is a major cause. More research is being done on these genes.

DNA mutations acquired during a man’s lifetime

Most DNA 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 is not perfect, and sometimes errors occur, leaving flawed DNA in the new cell. It is not clear how often these DNA changes might be random events, and how often they are influenced by other factors (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.

The development of prostate cancer may be linked to increased levels of certain hormones. High levels of androgen (male hormones, such as testosterone) promote prostate cell growth, and might contribute to prostate cancer risk in some men.

Some researchers have noted that men with high levels of another hormone, insulin-like growth factor-1 (IGF-1), are more likely to get prostate cancer. IGF-1 is similar to insulin, but it affects cell growth, not sugar metabolism. However, other studies have not found a link between IGF-1 and prostate cancer. Further research is needed to make sense of these findings.

Some studies have found that inflammation in the prostate may contribute to prostate cancer. One theory is that inflammation might lead to cell DNA damage, which might in turn push a cell closer to becoming cancerous. More research in this area is needed.

Exposure to causing chemicals can cause DNA mutations in many organs, but these factors have not been proven to be important causes of mutations in prostate cells.

What are the risk factors for prostate cancer?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

But risk factors don’t tell us everything. Many people with one or more risk factors never get cancer, while others who get cancer may have had few or no known risk factors.

We don’t yet completely understand the causes of prostate cancer, but researchers have found several factors that might affect a man’s risk of getting it.

Age

Prostate cancer is very rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50. About 6 in 10 cases of prostate cancer are found in men over the age of 65.

Race/ethnicity

Prostate cancer occurs more often in African-American men and in Caribbean men of African ancestry than in men of other races. African-American men are also more than twice as likely to die of prostate cancer as white men. Prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. The reasons for these racial and ethnic differences are not clear.

Geography

Prostate cancer is most common in North America, north-western Europe, Australia, and on Caribbean islands. It is less common in Asia, Africa, Central America, and South America.

The reasons for this are not clear. More intensive screening in some developed countries probably accounts for at least part of this difference, but other factors such as lifestyle differences (diet, etc.) are likely to be important as well. For example, men of Asian descent living in the United States have a lower risk of prostate cancer than white Americans, but their risk is higher than that of men of similar backgrounds living in Asia.

Family history

Prostate cancer seems to run in some families, which suggests that in some cases there may be an inherited or genetic factor. Having a father or brother with prostate cancer more than doubles a man’s risk of developing this disease. (The risk is higher for men who have a brother with the disease than for those with an affected father.) The risk is much higher for men with several affected relatives, particularly if their relatives were young when the cancer was found.

Gene changes

Scientists have found several inherited gene changes that seem to raise prostate cancer risk, but they probably account for only a small percentage of cases overall. For example:

·  Inherited mutations of the BRCA1 or BRCA2 genes raise the risk of breast and ovarian cancers in some families. Mutations in these genes may also increase prostate cancer risk in some men.

·  Men with Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC), a condition caused by inherited gene changes, have an increased risk for a number of cancers, including prostate cancer.

Other inherited gene changes can also raise a man’s risk of prostate cancer. Recently, some common gene variations have been linked to a higher risk of prostate cancer. Studies to confirm this are needed to see if testing for the gene variants will be useful in predicting prostate cancer risk.

Diet

The exact role of diet in prostate cancer is not clear, but several factors have been studied.

Men who eat a lot of red meat or high-fat dairy products appear to have a slightly higher chance of getting prostate cancer. These men also tend to eat fewer fruits and vegetables. Doctors aren’t sure which of these factors is responsible for raising the risk.

Some studies have suggested that men who consume a lot of calcium (through food or supplements) may have a higher risk of developing prostate cancer. Dairy foods (which are often high in calcium) might also increase risk. But most studies have not found such a link with the levels of calcium found in the average diet, and it’s important to note that calcium is known to have other important health benefits.

Obesity

Most studies have not found that being obese (very over-weight) is linked with a higher overall risk of getting prostate cancer.

Some studies have found that obese men have a lower risk of getting a low-grade (less dangerous) form of the disease, but a higher risk of getting more aggressive prostate cancer. The reasons for this are not clear.

Some studies have also found that obese men may be at greater risk for having more advanced prostate cancer and of dying from prostate cancer, but not all studies have found this.

Smoking

Most studies have not found a link between smoking and prostate cancer risk. Some research has linked smoking to a possible small increase in the risk of death from prostate cancer, but this finding will need to be confirmed by other studies.

Workplace exposures

There is some evidence that fire-fighters are exposed to substances (toxic combustion products) that may increase their risk of prostate cancer.

Inflammation of the prostate

Some studies have suggested that prostatitis (inflammation of the prostate gland) may be linked to an increased risk of prostate cancer, but other studies have not found such a link. Inflammation is often seen in samples of prostate tissue that also contain cancer. The link between the two is not yet clear, but this is an active area of research.

  

Sexually transmitted infections

Researchers have looked to see if sexually transmitted infections (like gonorrhea or chlamydia) might increase the risk of prostate cancer, because they can lead to inflammation of the prostate. So far, studies have not agreed, and no firm conclusions have been reached.

Vasectomy

Some studies have suggested that men who have had a vasectomy (minor surgery to make men infertile) have a slightly increased risk for prostate cancer. But other studies have not found an increased risk among men who have had this operation. Research on this possible link is still under way.