Gene linked to aggressive prostate cancer identified

December 12th, 2007 - 3:26 pm ICT by admin  

Washington , Dec 12 (ANI): Two genome-wide association studies have found that a genetic variant of the DAB2IP gene raises the risk of aggressive prostate cancer.

The study was carried out by research teams from the Translational Genomics Research Institute (TGen), Wake Forest University School of Medicine, the Karolinska Institute in Stockholm , Sweden , and Johns Hopkins Medical Institutions made the discovery jointly.

It was led by John Carpten, Ph.D., director of TGens Division of Integrated Cancer Genomics.

The DAB2IP gene was suspected to be involved in tumor suppression, indicating that such a protective mechanism may go awry in men with the variant form.

This finding may help doctors to design specific treatment depending upon the genetic makeup of the patient.

Both genetic and environmental factors play a pivotal role in the development of prostate cancer, and some of the consistent genetic factors have been identified only recently. It is still unclear, if men who are genetically prone to the disease have a greater tendency to get more aggressive disease than men who are not.

Because there is no way to tell whether a person has or will have the aggressive version versus the mild version of prostate cancer, both forms are treated the samewith radiotherapy or surgery to remove the prostate gland, said Carpten.

He added: The identification of this genetic variant could lead to better risk assessment for aggressive disease, providing doctors with more information on how to best treat men who may be diagnosed with prostate cancer,

The researchers, after analyzing 3,159 samples, concluded that men having the DAB2IP variant seem to be carrying almost 36 pct increased risk of advanced prostate cancer.

In most cases, prostate cancer is not a death sentence, but it would be ideal to identify men with an aggressive form of disease, said Jianfeng Xu, M.D., Dr.PH, a senior author and a professor of epidemiology and cancer biology at Wake Forest University School of Medicine.

He added: Our finding suggests the possibility of developing a blood test to gauge disease type so doctors could decide if more aggressive treatment is needed.

DNA samples from 500 men with advanced prostate cancer and 500 healthy men of the same age were analyzed in Sweden .

Entire genome was examined for more than 550,000 single nucleotide polymorphisms (SNPs), which are locations on chromosomes where a single unit of DNA, or genetic material, may vary for different persons.

Then they analysed 60,000 SNPs that have also been evaluated by a similar study conducted by the National Cancer Institute (NCI) called Cancer Genetic Markers of Susceptibility (CGEMS). This evaluation pointed out seven SNPs appearing to be linked to disease aggressiveness.

Also, researchers screened another 1,242 men with advanced disease and 917 healthy men who were part of a research project at Johns Hopkins Medical Institutions. This group included both African and European Americans.

With the help of these multiple screenings, it was found that the variant form of DAB2IP is linked with an increased risk of having aggressive disease.

Senior authors Henrik Gronberg, M.D., Ph.D., a professor of epidemiology from Karolinska Institute, and William Isaacs, Ph.D., a professor of urology at Johns Hopkins Medical Institutions owed the results to advances in technology allowing them to take a more systematic approach to looking at the entire genome.

Instead of solely studying genes that they suspect may be related to disease susceptibility, they can study the entire genome and look for associations.

By using state-of-the-art technologies, we can find genes that were not previously known or thought to be involved with disease risk, said David Duggan, Ph.D., head of TGens Advanced Genomics Technology Lab.

He added: If we can then learn more about the proteins they produce, it could lead to new understanding about disease mechanisms and new treatments.

The study was reported in the Journal of the National Cancer Institute. (ANI)

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