Why Prostate Cancer may Not Run in Families

Having a brother with the disease may not increase a man’s risk after all.

When a man’s brother is diagnosed with prostate cancer, his initial reaction is probably sympathy and an offer to help—but a quick second response is likely something along the lines of, “Uh-oh, I’m next.”

In two dozen studies (reviewed in this 2003 paper), having a relative with prostate cancer increased a man’s risk of getting the disease himself, and the biggest increased risk—between double and quadruple the risk, for an average among the studies of a 2.87-fold increased chance—was among those men whose brother had prostate cancer. (If a man’s father had the disease, his risk of also getting it was 2.12 times greater than if his father did not have prostate cancer.) Those findings, usually communicated through doctors who ask about a man’s family’s medical history, have led to a widespread belief that the increased risk is real and probably genetic.

Not so fast. In a new study of more than 35,000 men, scientists reach a very different—and reassuring—conclusion. The apparent increased risk of prostate cancer among men who had a brother diagnosed with the disease does not necessarily reflect the presence of a cancer-causing genetic mutation, as everyone has assumed. (In fact, scientists have not identified any reliable genetic markers of prostate-cancer risk.) Instead, the increased risk reflects the fact that when one brother is diagnosed, the other(s) run out and get a PSA exam, scientists led by Ola Bratt of Helsingborg Hospital in Sweden conclude in a study published online in the Journal of the National Cancer Institute.

Prostate cancer is a mess to understand for several reasons. After widespread PSA testing was introduced around 1990, the incidence of low-risk prostate cancer soared in the U.S. and Western Europe. There wasn’t a sudden epidemic of the disease; a man’s lifetime risk of dying of prostate cancer has remained the same, at about 3 percent, for 30 years. Instead, more prostate cancers are being detected: the lifetime risk of being diagnosed with it has risen from 9 percent to 16 percent.

Most of these cancers would not have produced symptoms for years, and some would have remained innocuous until the man died of something else. Autopsies show that 70 percent of men who die in their 60s have prostate cancer. Most never knew it, let alone were harmed by it. (That has led to the adage that if men live long enough, they’ll all have prostate cancer, but many fewer will die from it.) The popularity of PSAs, in other words, has skewed the public’s—and scientists’—sense of how common prostate cancer is.

Knowing this, Bratt’s team studied 22,511 brothers of 13,975 men who were diagnosed with prostate cancer between 1996 and 2006. They were more likely to have a PSA than men without a diagnosed brother—so much so, the scientists conclude, that it “will inflate family history as a risk factor for prostate cancer.”

In an accompanying editorial in JNCI, Ian Thompson of the University of Texas Health Science Center at San Antonio and colleagues point out that the idea “that a family history of prostate cancer increases a man’s risk of a diagnosis of this disease is now entrenched in the medical literature”—and in the public mind. Interestingly, although doctors have known about prostate cancer for decades, it is only recently that they began tying it to family medical history. Between 1977 and 1986, there were seven scientific papers on the link (0.7 papers per year). Between 1987 and 1996, there were 79 (7.9 per year). Between 1997 and 2006, there were 458 papers (46 per year). In the past four years, there have been 65 publications per year.

“Why did it take us until the mid-1980s to fully recognize ... the familial association [with prostate cancer]?” Thompson asks rhetorically. “In the PSA era, a man with a brother or father with prostate cancer was more likely to be screened ... Against the background of an enormous number of undiagnosed (but diagnosable) prostate cancers, this simple decision could lead to a prostate biopsy and exaggerate the link between family history and prostate cancer.”

Men whose brothers are diagnosed with prostate cancer can therefore feel a lot less anxious. They should not feel that their shared genes will doom them, and should think twice about rushing off to get a PSA—whose risks and benefits remain so uncertain that the U.S. Preventive Services Task Force concluded that it could not recommend routine screening for any man, and recommended that men 75 or older not get a PSA.

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