What causes prostate cancer?
No one knows precisely what causes prostate cancer. But that doesn’t mean it’s a total mystery, either. Genetic defects play a role in the development of any cancer, as do carcinogens (substances that cause DNA damage). In some instances, the defects are inherited, meaning that they affect DNA in the parent’s sperm or egg cells (which are also called germ cells) and carry through into the developing baby. These inherited (germline) defects will be present in every cell of the body, but their cancer-causing effects tend to be selective for specific organs, including the prostate.For example, the same germline defects in the BRCA1 and BRCA2 genes that boost the risk of breast and ovarian cancer in women have also been linked to aggressive, hard-to-treat prostate cancers that affect younger men. BRCA genes ordinarily repair DNA damage. When those genes are defective, DNA damage can accumulate inside cells that, in turn, grow abnormally and form tumors. Roughly a quarter of all men who have aggressive prostate cancer have defects in one or both of these genes, but most commonly in BRCA2 alone. DNA repair defects aren’t limited to just BRCA: investigators have found dozens of inherited mutations affecting numerous DNA repair genes that could potentially be involved in prostate cancer. Research published in 2019 found that men with aggressive prostate cancer are three times more likely to have defective DNA repair genes than men whose tumors are growing more slowly.
Other germline genetic defects implicated in prostate cancer occur in the ATM gene (which helps regulate cell growth), in the HOXB13 gene (which plays a role in prostate development), in the PALB2 gene (which coordinates with BRCA2 in the DNA damage response), in the CDK12 gene (which helps to stabilize the cell genome), and in so-called mismatch repair genes (which repair DNA errors that allow cancer cells to survive for unusually long durations and to resist chemotherapy). Men with advanced prostate cancer can also have gene mutations that boost their sensitivity to testosterone, making their prostate cancer cells grow more aggressively. If they have metastatic cancer and defects in a gene called CHEK2, they are not as likely to respond to hormonal treatments that aim to blunt testosterone’s effects. Research published in 2022 showed that men with localized tumors that are confined to the prostate gland rarely have germline mutations. Fortunately, as many as 90% of the gene defects that have been found so far in advanced prostate cancer can be targeted with existing drugs or drugs that are now in clinical trials.
Doctors screen for germline mutations in saliva, urine, and blood samples. But other genetic defects, which are not inherited, can develop if chemicals, radiation, or inflammation alter DNA. These somatic mutations, as they are known, are found only in the cells descending from the cell that was originally mutated, and some of them may cause prostate cancer. Doctors look for them in tumor samples.
