New Genetic Markers Point to Increased Risk of Prostate Cancer

Scientists from the Cancer Genomics Research Laboratory and colleagues have pinpointed 23 new genetic markers associated with increased risk of prostate cancer, the second leading cause of cancer death in American men.

Knowing who is at high risk for the disease can help doctors identify individuals who are more likely to require aggressive screening and follow-up.

The research, published in Nature Genetics, analyzed more than 10 million genetic markers (single-nucleotide polymorphisms) from more than 43,000 men with prostate cancer and nearly 44,000 men without the disease.

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From their analysis, the group identified 23 new genetic variants linked to the disease. These, together with 76 previously known genetic markers, account for one-third of the inherited risk of prostate cancer in individuals of European ancestry.

Participants in the study came from Australia, Ghana, Japan, the United Kingdom, and the United States. Fifteen of the genetic variants were associated with increased prostate cancer risk among European descendants. Seven markers were for non-European populations; and one was linked to early-onset of the disease, in men under age 55.

In part of the study, the scientists looked specifically for genetic associations linked to increased risk of aggressive prostate cancers, which grow and spread relatively rapidly and become life-threatening. The ability to screen for these high-risk tumors — as opposed to slow-growing, low-risk malignancies — would be valuable for preventing overtreatment. This is a pressing issue in patient care.

The analysis found no genetic associations that would discriminate between the aggressive and relatively benign forms of the disease.

The study did, however, isolate men who are the top 10 percent at highest risk for prostate cancer, which in the future could help reduce over-diagnosis at the doctor’s office and improve treatment strategies.

An estimated one in seven men in the United States will be diagnosed with prostate cancer in his lifetime. The mortality rate has declined about 45 percent since screening began using prostate specific antigen levels as a guide. But this test does not tell if the disease is high- or low-risk, meaning that many patients get unnecessary treatments (some with side effects) out of an abundance of caution. Additional, ongoing studies will address these outstanding questions.

The current research was co-led by Stephen J. Chanock, M.D., Director of the National Cancer Institute (NCI) Division of Cancer Epidemiology and Genetics and director of NCI’s Cancer Genomics Research Laboratory. Bioinformatics analyst Zhaoming Wang of the Frederick National Laboratory for Cancer Research and a member of the genomics research lab was among the many collaborators on the research.