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 environmental carcinogens that cause DNA damage.
Defects in the BRCA1 and BRCA2 genes known to boost the risk of breast and ovarian cancer have 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. In 2015 scientists published the results of a study showing that about a quarter of all men who have aggressive prostate cancer have defects in either BRCA1 or BRCA2 or in both genes, but most commonly in BRCA2 alone. DNA-repair defects aren’t just limited to BRCA: a study in 2016 found that 84 inherited mutations affecting 16 different DNA repair genes could potentially be involved, although men with advanced metastatic prostate cancer would likely have just one or a few of them.
Other 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), 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, a hormone that makes prostate cancer cells grow more aggressively. 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.
Risk factors
Risk factors are sometimes confused with causes. Risk factors are characteristics or conditions that increase the odds of getting a disease. So while the causes of most prostate cancers remain elusive, innumerable studies have identified risk factors. Here are some of them.
Age. The risk of prostate cancer increases with age. About 90% of cases are diagnosed in men over age 55, and the median age for diagnosis is 66, according to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data. The number of cases diagnosed tapers off in men ages 75 and older, partly because men that age aren’t screened as often.
Family history. Prostate cancer runs in families. A man who has a father or brother with prostate cancer is two to three times more likely to have prostate cancer—or to develop the disease in the future—than a man with no first-degree male relatives with the disease. And if two or more first-degree relatives have a prostate cancer history, the risk is five to 10 times greater than for the man with no affected first-degree relatives. The age at which relatives are diagnosed has some bearing on the risk calculations. Diagnosis before age 60 increases the risk, probably because early-onset prostate cancer is more likely to be caused by inherited mutations.
Race. African American men have the highest prostate cancer incidence and death rates of any group in the United States. The incidence of prostate cancer among African American men is almost 70% higher than it is among white men (203.5 vs.121.9 per 100,000 men), and the death rate from the disease for African American men is more than double the rate for their white counterparts (44.2 vs. 19.1 per 100,000 men).
Nationality. Prostate cancer incidence varies greatly among countries. The highest rates are in Australia and New Zealand, Western Europe, Canada and the United States, and the Caribbean, while the lowest rates are in south central Asia (Thailand and India) and northern Africa.
Diet. Men who eat a lot of red meat or high-fat dairy products seem to have a higher risk of developing the disease. In fact, a 2015 study found that men who ate a mostly Western diet high in red and processed meats, fat, and dairy food had two-and-a-half times the risk of prostate cancer—and a 67% increased risk of death from any cause—as men who ate a diet rich in vegetables, fruits, fish, and whole grains. More recently, a 2016 study linked diets high in saturated fat—the type of fat found in fatty beef and cheese—to prostate cancers that are more aggressive, while a 2017 study found that diets rich in fruits, vegetables, legumes, nuts, and fish are protective against aggressive prostate cancers. Some studies have also found that high levels of calcium (much more than what is in the average diet) seem to increase the risk. Dr. Marc Garnick, editor in chief of the Annual, cautions his patients against taking more than 1,100 milligrams of calcium per day, as higher amounts can increase the risk of heart problems.
Eating too much, especially unhealthy foods, can lead to weight gain—and obesity seems to increase the risk of developing aggressive prostate cancer (as well as other types of cancer). Although it’s not entirely clear how obesity might contribute to prostate cancer, one theory involves insulin, the hormone that enables cells in the body to use energy from glucose and fatty acids in the blood. Excess weight causes people to develop insulin resistance, a condition in which cells become less sensitive to insulin’s effects. To compensate for this resistance, their bodies produce higher and higher levels of insulin over time. Insulin is a growth factor, so as the insulin level rises, it may help drive the out-of-control cell growth in cancer directly or through the action of related hormones called insulin-like growth factors.
Ejaculation frequency. In 2015, Harvard researchers reported the strongest evidence yet that men who ejaculate frequently have a lower risk of prostate cancer. In a large, ongoing study, men ages 20 to 29 and those 40 to 49 who ejaculated more than 21 times per month had a 20% lower prostate cancer risk than those who ejaculated four to seven times a month. It’s not clear why frequent ejaculation is protective, although some experts believe the release of semen flushes harmful substances from the prostate.
Other factors. Researchers have examined other factors that might play a role in the development of prostate cancer—including sexually transmitted diseases, prostatitis, and vasectomy—but study findings have been inconsistent, and no firm conclusions have been drawn.