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Has prostate cancer found its BRCA?

A newly discovered gene variation greatly increases a man’s odds of developing prostate cancer, but it is too early to say if the findings will be useful for genetic screening.

Most of the 240,000 new prostate cancers diagnosed each year appear in men without a strong family history of the disease. However scientists have known for years that prostate cancer runs in some families, yet they made little progress identifying genes that greatly increase a person’s risk of the disease.

So far nearly 50 gene variations have been linked to prostate cancer, but each one has a small influence on the disease and together these variations boost a person’s risk of prostate cancer by at most 4.2-fold, says Rosalind Eeles, a geneticist at the Institute of Cancer Research and The Royal Marsden Hospital in London who was not involved in the new study. It appears today in the New England Journal of Medicine.

The newly identified variation, which lies in a development gene called HOXB13, probably plays a more consequential  role in prostate cancer. Kathleen Cooney, at the University of Michigan in Ann Arbor, and her team discovered the variation in four families with a history of prostate cancer. All of the 18 men with prostate cancer carried the same variation. Cooney’s team found it by sequencing more than 200 genes on a swath of chromosome 17 that had been previously linked to hereditary prostate cancer.

Among a different group of 5,083 unrelated men with prostate cancer, 72 carried the mutation. Cooney’s team found just a single man out of 1,401 without prostate cancer with the mutation. Men with a family history of prostate cancer and who were diagnosed before the age of 55 were the most likely to possess the variation, Cooney notes.

The HOXB13 variation is likely to be linked to only a small proportion of prostate tumours, but it may prove useful in screening men with a family history of prostate cancer, says Cooney. “We’re optimistic that this could be important for patients and families and this might give an opportunity for early detection and treatment,” she says. Her team plans to secure intellectual property rights for genetic tests based on the findings.

Such a test could be similar to testing done for rare mutations in the genes BRCA1 and BRCA2 in women with a family history of breast or ovarian cancer. Certain mutations in those genes substantially increase a woman’s risk of those diseases.

Scientists will need to learn much more about the mutation before a test is ever developed. “What we need to do next is determine if you have a mutation in this gene how likely are you to get prostate cancer and at what age,” says Elaine Ostrander, a geneticist at the National Human Genome Research Institute in Bethesda, Maryland, who was not involved in the study. It is also unclear whether men with with the HOXB13  variation are more likely to die from prostate cancer than men without the variation, or whether their tumours are more aggressive, Cooney says.

Earlier this year, the United States Preventive Services Task Force determined that the prostate specific antigen (PSA) test commonly used as a screening tool in healthy men does not save lives and subjects men to unnecessary treatment (See Evidence is against PSA testing — but will that change anything?)

Ostrander expects scientists to find more mutations strongly linked to hereditary prostate cancer. Scientists studying families with a history of the disease have in the past homed in on relatively large portions of the genome. With next generation DNA sequencing, it is now feasible for scientists to sequence the hundreds of genes in these regions to narrow their searches. Cooley’s team is “the first off the blocks and I’m looking forward to seeing other mutations identified,” Ostrander says.

Image of a prostate tumour micrograph via Wikimedia Commons

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    Ed Yong said:

    The headline’s a little misleading, because prostate cancer’s BRCA is, well, BRCA.

    BRCA2 (and possibly BRCA1) is a high-risk prostate cancer gene.

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