Hereditary Prostate Cancer Risk: A Major Gene Mutation Is Found
Scientists William Isaacs, right, and Charles Ewing
found that men who inherit the HOX B13 mutation
are 10 to 20 times more likely to get prostate cancer
than other men, and at a younger age.Bill Isaacs might not have imagined it would take more than 20 years, but he knew he was in for a long, tough haul when he started searching for genetic links to cancer in families that had been devastated by prostate cancer. With the technology that existed in the late 1980s, it was a nightmare version of "find the needle in the haystack" – with millions of potential needles in hundreds, and then thousands, of haystacks. But Isaacs, Ph.D., his dedicated research team and soon, collaborators at other institutions, plugged away. It made sense that a major mutation had to be out there: Something was clearly different with these families, most of whose men tended to develop prostate cancer, and at a younger age. But for a very long time, the genetic Holy Grail of a "highly penetrant" gene – a mutation that, if inherited, will dramatically raise a man's risk of developing prostate cancer – proved elusive.
The scientists knew a major gene
His research has been generously supported by donors including Mr. P. Kevin Jaffe and the Peter Jay Sharp Foundation. "We have never seen anything like this before," adds Walsh, a co-author of the study. "It all came together to suggest that this single change may account for at least a portion of the hereditary form of prostate cancer." Among other implications, this discovery may lead to a genetic test that could help save lives as men who turn out to have this mutation begin regular screening, perhaps even starting as early as their thirties.
Patrick Walsh, who has been seeing increasingly younger men with prostate cancer, is struck by how many of them have a family history of the disease. One of his patients, a 49-year-old man, has an unforgettable legacy: Every male in his family has died of prostate cancer: His father, his father's three brothers, and his grandfather. Walsh, then Director of the Brady, launches the first of a series of genetic studies.
A study of 691 of Walsh's radical prostatectomy patients demonstrates that a family history of prostate cancer is a major factor that increases risk of the disease. Men who have a father or brother with the disease have a twofold higher risk, and this increases if there are three or more first-degree relatives affected.
Based on the data collected in Walsh's families, a study published in the Proceedings of the National Academy of Sciences demonstrates for the first time that the aggregation of cases in families is caused by Mendelian inheritance of a rare gene.
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