Sep 29, 2009 - Research

Researchers Find More Genetic Variants Associated With Prostate Cancer



In the United States, prostate cancer affects about one in every six men.   Genomewide association studies to find common genetic variants associated with this disease have been particularly successful.

More than a dozen SNPs have been associated with prostate cancer, but researchers calculate that these variants represent only a tiny fraction of the genetic component of the disease.

Filling the Gap

To fill in the genetic gaps, researchers are turning to studies that include larger numbers of participants than ever before.   The hard work is paying off, as seen in four recent reports of Nature Genetics.   These analyses, based on the DNA of tens of thousands of men, have added at least 12 new variants to the roster of prostate cancer-associated SNPs.

One of the most striking features of these new studies is that they have identified two new SNPs on chromosome eight in a region known as 8q24.   Three other variants in this same region have already been linked to prostate cancer in both African American and European samples.   Other SNPs in the 8q24 region have been associated with breast, bladder, and colorectal cancer.

The bounty of cancer-related SNPs in the 8q24 region is puzzling to scientists because there are no actual genes in this stretch of DNA.   The closest gene, MYC, is known to be involved in cancer, but so far, there is no evidence that the cancer-associated 8q24 SNPs are affecting MYC. Future research will hopefully identify what these SNPs are doing and how they affect cancer risk.

GWAS Limitations

Even though prostate cancer genome-wide association studies have been fruitful, critics such as John Witte of UCSF argue that the findings may not be clinically useful (read his February Nature Genetics review of prostate cancer genomics here).

But that doesn’t mean that looking for variants associated with prostate cancer should be abandoned.   Finding SNPs associated with the disease could lead scientists to new treatments.

There is also the possibility of finding variants that don’t just predict whether someone is at risk for prostate cancer but whether they are at risk for a particularly aggressive form of the disease. This could help doctors discriminate between those men whose cancers require immediate treatment and those who can avoid the side effects of surgery and radiation in favor of “watchful waiting.”

“There is clear clinical utility in identifying markers that can distinguish which prostate tumors will progress rapidly and be life-threatening versus those that are relatively latent and may not substantively impact a man’s health,” Witte writes.

More Data Needed

As has been the case with most other studies looking for genetic variants associated with prostate cancer, none of the four new studies found an association between the identified SNPs and disease severity. Scientists have suggested that this indicates the studies are mainly finding variations associated with increased risk for cancer initiation.

More large studies will be needed to find disease aggression-associated variants, and researchers will need to focus on SNPs correlated with disease recurrence following treatment and/or mortality instead of just the presence or absence of disease.

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