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5 Genes Linked to Aggressive Prostate Cancer

5 Genes Linked to Aggressive Prostate Cancer Study Could Lead to Test That Determines Which Patients Need Aggressive Treatment WebMD Health News By Salynn Boyles Reviewed by Laura J. Martin,...

Aug. 16, 2011 -- Researchers in Seattle and Sweden have identified five inherited genetic markers that could help spot men with the most aggressive and deadly forms of prostate cancer.

They say the discovery may lead to a simple blood test to help distinguish between men with prostate cancer who need aggressive treatment and those who don't.

Overtreatment is a major concern in prostate cancer in part because the most widely used therapies -- surgery and radiation -- can cause lifelong side effects including impotence and incontinence.

Genetic markers that can distinguish between patients with aggressive and non-aggressive prostate cancers are urgently needed, Janet L. Stanford, PhD, of the Fred Hutchinson Cancer Center tells WebMD.

She adds that the markers identified by her research team represent the first evidence that gene variants known as single-nucleotide polymorphisms (SNPs) play a role in prostate cancer progression.

Identifying High-Risk Patients

SNPs are single-letter variations within the four-letter DNA alphabet. They are increasingly recognized as having an important role in disease progression.

"Ultimately, these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile," Stanford says in a news release.

About 200,000 prostate cancers are diagnosed each year in the U.S. About 30,000 men die of the disease.

Often prostate cancer is slow growing. Men with the disease often die of other causes before the malignancy turns deadly.

But prostate cancer patients are usually treated with either surgery or radiation because there is no reliable way to determine if an individual patient's prostate cancer is slow growing or aggressive, William Phelps, PhD, of the American Cancer Society tells WebMD.

In the newly published study, Stanford and colleagues analyzed DNA samples from 1,309 Seattle-based prostate cancer patients, looking for gene variants suspected of being involved in tumor progression.

The analysis of 156 candidate genes identified 22 SNPs linked to prostate cancer-specific death.

In a separate analysis, the researchers examined these variants in stored DNA samples from close to 2,900 prostate cancer patients in Sweden who had been followed for an average of six and a half years.

Five of the 22 SNPs emerged as being significantly associated with death from prostate cancer in this larger group of patients.

The variants included:

  • LEPR, a leptin receptor gene involved in tissue growth, inflammation, the development of blood vessels and bone density. The bone density association may explain why prostate cancers often spread to the bone before spreading to other organs, the researchers suggested.
  • RNASEL, a gene associated with programmed cell death, inflammation, and the ability of cells to multiply rapidly.
  • Interleukin 4, which is associated with tumor growth, blood vessel development, and cancer cell migration.
  • Cytochrome 1, which is a gene involved in circadian rhythms, which could affect testosterone levels.
  • ARVCF, a gene that is involved in cell communication, which has previously been linked to cancer progression.

 

Reducing Overtreatment for Prostate Cancer

Patients who carried four or all five of the SNPs had a 50% higher risk of dying from their cancer than patients who had two or fewer of the SNP variants.

The next step is to confirm the findings in different groups of patients and to determine if these five SNPs or any of the other identified gene variants are useful for predicting death from prostate cancer, Stanford says.

The study was published online today and will appear in the September issue of Cancer Epidemiology, Biomarkers and Prevention.

Phelps says finding better tests to identify patients who will benefit from therapy is an important goal for reducing the harms from prostate cancer overtreatment, along with finding more effective targeted therapies that do not have life-altering side effects.

"There has been an explosion of research examining targeted cancer therapies, and while we haven't struck pay dirt in prostate cancer yet, I think it's just a matter of time," he says.

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