by Cecilia Lacks, PhD
Researchers are looking for genetic hot spots in prostate cancer patients, and it appears that they found some in a marker area 8q24 (a region labeled 24 on the long arm of chromosome 8).
"What we're looking for are places where a frequency of genetic changes match or correlate with a frequency of prostate cancer development, and we have strong evidence to believe we’ve found an area," Brian Helfand, MD, PhD, said.
This finding, while only a beginning, holds great promise for understanding what genetic changes cause prostate cancer and what interventions might prevent it from developing.
Helfand explained that in the future, the knowledge of who might be known carriers of the markers would let these men know they are not candidates for any "watchful waiting" program and they should be followed closely after their radical prostatectomy.
Helfand, who works with Dr. Catalona, is co-investigator of a study supported by the Urological Research Foundation that looked at the tissue and blood samples of 551 men (patients of Dr. Catalona) with prostate cancer.
Helfand said his findings showed that carriers of the genetic variant on chromosome 8q24 had a 40% chance of having a close family member with prostate cancer compared with a 20% chance among men without the variant.
In this group of men with CaP, 8q24 variant carriers also had a cancer that was more likely to spread to the lymph nodes and more difficult to cure with surgery alone.
Statistically, they also had higher Gleason scores, extracapsular tumor extension, and seminal vesicle invasion.
In the past, researchers looked at specific DNA codes of known genes and at variations within these genes called alleles.
This research is different in that the researchers examined sequences in an area of the genome that does not encode any known gene and, in that area, looked at the variations or alleles present.
Most people have seen the very long and involved list of alphabet letters that represent a genetic code. In one area a part of a code might be CCATT but in a substantial number of men with prostate cancer, that code is CAATT.
The place where the changed code is spotted (in this example it is the second letter; C to A) is called an allelic variation.
Looking for variations that might be connected to a specific disease is arduous and complicated. It can be compared to looking for, not just the needle in a haystack but, the head of the needle in a haystack.
Chromosome 8, for example, has about 146 million base pairs. Only the development of new technology made the search possible.
In the case of 8q24, a group of scientists and doctors from around the world, including Dr. Catalona, participated in a study with an Icelandic company, deCODE Genetics, to identify genetic risks for prostate cancer. They found a statistical connection between variant alleles in the area of 8q24 and men with prostate cancer.
This time is the first that a genetic mutation associated with prostate cancer has been found in a large population of prostate cancer patients.
Now that the findings have been replicated in more than 10,000 patients at several respected research institutions, numerous research studies are looking at this genetic area: its relationship to prostate cancer, its potential for treatment recommendations, and its possibility for changing or preventing the development of prostate cancer.
Scientists don't understand yet is how or why these genetic variations affect prostate cancer risk, but some practical applications seem obvious with these new findings.
"They may be used to develop some of the first clinical genetic tests for prostate cancer susceptibility and aggressiveness. And they may provide fundamental insights into the causes and development of prostate cancer, insights that could help us identify new molecular targets for treatment and prevention."
"But they will require results from many more studies and testing in clinical practice to prove their usefulness. A lot of complex work has yet to be done," Dr. Catalona said.