Inherited genetic variation linked to aggressive prostate cancers

In collaboration with the Press Association

Researchers have discovered five inherited genetic differences that can increase the risk of men developing an aggressive form of prostate cancer.

The researchers hope that their findings could eventually pave the way for a simple blood test to identify patients who need aggressive treatment and those who would benefit from a more conservative monitoring before treatment approach.

The international research team, led by Dr Janet L Stanford from the Hutchinson Center's Prostate Cancer Research Programme, looked at DNA samples from more than 1,300 prostate cancer patients in Seattle.

They examined single-nucleotide polymorphisms (SNPs) - variations in just one 'letter' of a person's DNA sequence that are often linked to inherited characteristics - including a raised or lowered risk of cancer.

Finding that 22 of the SNPs were more common among study participants who had more aggressive forms of prostate cancer, the group checked their results against data from 2,875 prostate cancer patients in Sweden.

The team found that five of the original 22 SNPs were more likely to be present in men who had died of prostate cancer (and hence were likely to have had aggressive disease). They were found near or in five genes that may affect prostate cancer progression: LEPR, RNASEL, IL4, CRY1 and ARVCF.

Patients with four or all five of these genetic markers had a 50 per cent higher risk of dying from their prostate cancer than those with two or fewer.

The results show that the more of the SNPs a man inherited, the greater his risk of dying from prostate cancer.

The findings were published in the Cancer Epidemiology, Biomarkers and Prevention journal.

Dr Laura McCallum, Cancer Research UK science information officer, said: "These results need to be confirmed in different populations of men, but if successful could help identify men with more aggressive forms of prostate cancer. If doctors can tell how a cancer will respond to treatment from the outset, they can make the best possible decisions about the care of each man with the disease."

"These findings also offer new insights into the genetic causes of prostate cancer - the more we learn about how the disease develops, the greater chance we have of identifying people at risk and finding new treatments."

Professor Doug Easton, director of Cancer Research UK's Genetic Epidemiology Unit at the University of Cambridge, said: "Work by Cancer Research UK and others has uncovered over 30 SNPs that are associated with prostate cancer risk. This new study is particularly interesting because it links other DNA changes with prostate cancer aggressiveness or survival. Before any test based on these results is developed though, we need to see if these early results are confirmed in larger studies.

"A challenge with all such studies is to translate potential associations into tests that are clinically useful. My own group is working on a very large study of over 40,000 patients to uncover links that can one day be exploited in the clinic."

Copyright Press Association 2011

References

  • Lin, D. W. et al. Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality. Cancer Epidemiology, Biomarkers and Prevention. DOI: 10.1158/1055-9965.EPI-11-0236