Prostate Cancer Can Be Inherited Since 1992, the presence of a familial prostate cancer gene (or genes) had been suspected; the undeniable link between a family history of prostate cancer and a man's risk of developing the disease was characterized as the distinct phenomenon of Hereditary Prostate Cancer (HPC). Investigators from the Brady Urological Institute, in collaboration with scientists from the National Human Genome Research Institute and from Umea University in Sweden, first linked the disease to a gene at a specific location on chromosome 1. This particular gene is probably responsible for about one-third to half of cases of hereditary prostate cancer and only about 10 percent of all cases of prostate cancer are thought to be purely hereditary. But many scientists believe that the defective gene or mechanisms involved in hereditary cancer are the same ones that somehow go askew in "sporadic" cancer, disease that just develops over the course of a lifetime he kind most men get. (Most scientists believe that cancer happens because of a combination of "hits" at least one genetic aberration, plus one more things environmental, such as a poor diet or smoking. Think of a genetic slot machine, in which to develop disease you need to get two, three or five oranges in a row; having a bad gene is worth at least one orange.) Identifying the gene enables us to identify the families that carry this mutation and in doing so, to identify men who are at high risk for developing the disease, so prostate cancer can be detected in time to cure it. Men with HPC tend to develop the disease far sooner even as young as their late thirties or early forties than other men. Unfortunately, by the time these men even start routine screening for prostate cancer, it may already be too late to cure it. An estimated 250,000 American men may carry the defective gene, named HPC1. These men appear to have extremely high odds a nearly 90 percent likelihood of developing prostate cancer by age 85. The gene doesn't appear to discriminate. It may be active over a wide variety of geographic regions and ethnic backgrounds. In the study, the susceptibility was found in Caucasian and black men scattered throughout the United States, as well as Caucasians in Canada and Sweden. How the Search Began Prostate cancer is a confoundingly common disease. That's why, for years, scientists downplayed the idea that (just like more conspicuous illnesses such as hemophilia) it could be inherited even though it was known to run in families. Thirty years ago, Mormon genealogists in Utah noted that prostate cancer seemed to "cluster" in families and that, among familial cancers, this clustering of prostate cancer was actually more common than breast or colon cancer (yet both of these were recognized to have a hereditary predisposition). But for some reason, prostate cancer got lumped in the category of ailments that simply come with old age. With this perception muddying the water, these observations went relatively unexplored for a couple of decades largely because prostate cancer was so common in older men. In the 1980s, Patrick C. Walsh, chief of urology at Johns Hopkins Hospital, began to see increasingly younger men for surgical treatment of prostate cancer, and was struck by how many of them had a family history of the disease. Then, in 1986, he met a 49yearold patient with a tragic, unforgettable legacy: "He told me that every male member of his family had died of prostate cancer: His father, his father's three brothers, and his grandfather," says Walsh. "At that time, virtually every physician in the United States could tell you that a woman's risk for breast cancer was increased twofold if her mother or sister had it. I wondered why similar information wasn't available about prostate cancer." So Walsh set out to find some answers, initiating the first of a series of studies, ably led by Bob Carter, an MD-PhD student, and Gary Steinberg, a former resident, and aided by pediatric geneticist Barton Childs, MD, and genetic epidemiologist Terri Beatty. The first question: Would the observations that had been pretty much limited to Utah Mormons hold true with a larger, more diverse group of men? A study of 691 patients, who had come for a radical prostatectomy, confirmed that having a family history of prostate cancer did indeed increase a man's risk of developing the disease. Next, the researchers ruled out environmental factors; further, their results strongly suggested that increased susceptibility to prostate cancer could be inherited from either parent. They then went on to define and characterize hereditary prostate cancer, showing the clear link between family history and a man's probability of developing prostate cancer. (Briefly, if your father or brother has prostate cancer, your risk is two times greater than the average American man's, which is about 13 percent. It goes up from there: Depending on the number of affected relatives you have and the age at which they develop the disease, your risk could be as high as 50 percent if you are in a family that meets the criteria for HPC if you have at least three close relatives, such as a father and two brothers affected, or two relatives if both were younger than 55 years old; or if your family has disease in three generations a grandfather, father or brother.) Then came this study. Out of a pool of 2,500 families that met the criteria for HPC came an elite group of 91 families handpicked and rigorously screened by Walsh and behavioral scientist Sally Isaacs. Sadly, the families selected for the study were those hardest-hit by prostate cancer so there could be no mistaking hereditary cancer for "simply bad luck" in which several men in the same family happened to develop the disease. The families filled out detailed questionnaires about their health, occupations and family history, and sent blood samples to Hopkins. It was their DNA that pointed to the marker, or signpost for the gene. Until more is learned about HPC, men in HPC families should have a digital rectal examination and PSA test every year, beginning at age 40. |