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Five inherited genes point to risk of dying from prostate cancer

Kathleen Blanchard's picture

Now researchers can better predict when prostate cancer should be aggressively treated, versus monitoring, thanks to new research. Scientists have found five inherited gene variants that can make prostate cancer deadly.

The discovery means it may be possible to identify men at highest risk with blood tests that can identify the gene mutations, say researchers.

The finding is significant for men who may not need aggressive prostate cancer treatment. Surgery or radiation that can lead to impotence or urinary leakage. Many prostate cancer patients may require no treatment.

Prostate cancer SNPs genotyped in American and Swedish men

The study, from Janet L. Stanford, Ph.D., co-director of the Fred Hutchinson Center’sProgram in Prostate Cancer Research and a member of its Public Health Sciences Division, identifies five SNPs - single-nucleotide polymorphisms, or genetic mutations that are thought to contribute to the development or spread of prostate cancer, in two separate studies.

For the study, researchers analyzed genes in 1,309 prostate cancer patients in the Seattle area, age 35 to 74, at the time of diagnosis.

Among 937 SNPs in 156 candidate genes, 22 SNPs were found to be associated with lethal forms of prostate cancer.

In a second study, the 22 SNPs were genotyped in 2,875 prostate cancer patients in Sweden, age 35 to 74. Five of the gene variants were again found to be associated with deadly prostate cancer.

Dr. Stanford explains, “The panel of markers we’ve identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. 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.

The five genes identified for lethal prostate cancer included:

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• LEPR – The leptin receptor gene, which helps control tissue growth, inflammation, blood-vessel development and bone density.

• RNASEL – A gene which is linked to hereditary prostate cancer and associated with programmed cell death, known as aptosis.

• IL4 – The Interleukin 4 gene is linked to growth of tumors, development of new blood vessels that fuel cancer growth and spread to other areas of the body.

• CRY1 – cryptochrome 1 is thought to affect circadian rhythm and hormone levels that can also fuel prostate cancer growth and progression

• ARVCF – a gene that signals other cells, contributing to prostate cancer progression when it is overexpressed.

“While previous studies have suggested that genetic background influences prostate cancer outcomes, this is the first study to validate genetic markers associated with lethal disease,” Stanford said.

Men studied had a 50 percent higher chance of dying from the disease when they carried four or five of the gene variations.

The researchers are planning further studies to validate their findings. The finding could lead to a simple blood test that can identify men at high risk of dying from prostate cancer. Understanding the role of inherited genes in prostate cancer progression could also lead to personalized treatment.


Cancer Epidemiol Biomarkers: doi:10.1158/1055-9965.EPI-11-0236
“Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality”
Daniel W. Lin, et al.
August, 2011