"This is a major step toward a better understanding of the factors responsible for prostate cancer, and would not have been possible without the intense effort and collaboration of a large number of scientists and patients in the U.S., Finland and Sweden" said Dr. Patrick C. Walsh, Urologist-in Chief at Johns Hopkins, who is an author on the paper.
The project's co-director Dr. Jeffrey Trent, of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH), agrees. "There are 200,000 to 300,000 new prostate cancer cases diagnosed each year, and 40,000 deaths annually. This finding is significant in that it accounts for perhaps 15 to 20 percent of 20,000 to 30,000 hereditary prostate cases, and with prostate cancer accounting for more than a third of all cancers that affect men, this is an important public health problem," said Trent.
The newly discovered gene is the second prostate cancer gene to be located by the international team, which is led by scientists at NHGRI and Johns Hopkins in collaboration with researchers at the University of Tampere in Finland, the University of Maryland, Umeň University in Sweden, and the Mayo Clinic in Rochester, MN. For this current study, more than 1500 affected men from over 360 families prone to prostate cancer were studied.
The first gene these researchers located, known as HPC1 (for human prostate cancer 1) is on chromosome 1, one of 22 pairs of non-sex human chromosomes. The X-chromosome gene will be called HPCX. Now that the scientists have mapped its location, they are studying several genes in that region to identify the precise location of the gene.
"There's none that jumps out at us and screams that it's the gene we're looking for," said
Dr. William Isaacs of Johns Hopkins, the project's co-director. "One of the X chromosome genes that people have been studying is the androgen receptor, which once seemed like a very good candidate gene because variations in the androgen receptor can increase prostate cancer risk. But its far away, essentially unlinked to the region we're looking at."
The study confirms researchers' long-held suspicion that the X chromosome might be important in prostate cancer. Since the 1960s, they have known that a man's risk of prostate cancer is higher if his brother has prostate cancer than if his father had the disease. That inheritance pattern is characteristic of genetic traits known to be on the X chromosome and passed from mothers to sons, such as muscular dystrophy and hemophilia. So one plausible explanation of the data has been that a gene for susceptibility to prostate cancer probably lies on the X chromosome. The specific mapping of the HPCX confirms that suspicion.
"Mapping HPCX brings us one step closer to understanding the origins of prostate cancer, at least in some families," said Dr. Francis Collins, NHGRI director, one of the paper's authors. "Now we need to identify the precise gene and the misspelling which correlates with risk of cancer. That will lead to better abilities to predict which men are at highest risk, which can allow them to be carefully watched for early signs of prostate cancer. Such predictive information can be very useful, since early diagnosis can be life-saving in this disease. In the longer term, understanding the molecular causes of prostate cancer is expected to usher in a new generation of more effective therapies."
"The finding points out once again the importance of facilitating multinational collaborative efforts to address a complex disease like cancer, particularly prostate cancer, which is among the hardest cancers to analyze from the standpoint of a geneticist," Trent said. The fact that prostate cancer is so common, he explained, increases the difficulty of distinguishing cancers due to an inherited mutant gene from those due to other causes. Another challenge for genetics, he noted, is that prostate cancer, even hereditary prostate cancer, is rarely diagnosed before the age of 60 and frequently much later-by which time a patient's parents and grandparents have died and cannot be studied.
NHGRI oversees the NIH's role in the Human Genome Project, an international research effort to develop tools for gene discovery.
For interviews with NHGRI researchers contact: Jeff Witherly: 301-402-8564 or Galen Perry: 301-402-3035.
Researchers at Johns Hopkins are asking individuals from families in which three or more close relatives have had prostate cancer and who wish to participate in a research study on the genetics of that disease to contact the study team at (410) 614-5434, or write to Dr. Patrick C. Walsh, Hereditary Prostate Cancer Study, Dept. W., Brady Urological Institute, Johns Hopkins University Hospital, Baltimore, MD 21287.
Howard University in Washington, D.C., with funding from the National Institutes of Health (NIH), has organized a national study network to find genes involved in hereditary prostate cancer (HPC) in African Americans. Howard University and NIH collaborate on this study with seven medical centers across the United States. To learn more, visit the study website at: http://www.nhgri.nih.gov/About_NHGRI/Dir/Prostate_Study/index.html or phone toll free at 1-888-218-6157.
For more information about prostate cancer, call the Cancer Information Service at 1-800-4-CANCER. Additional information is also available through the NHGRI web site at http://www.nhgri.nih.gov.