More than 160,000 new cases of prostate cancer are diagnosed in the United States each year, making it the second most common cancer in men after skin cancer, according to the American Cancer Society. It’s also among the most common causes of cancer death in men, second only to lung cancer. So it’s no wonder there’s a high demand for a better understanding of the genetic causes of the disease—insight that could lead to the development of genetic tests to identify who faces the highest risk.
A transatlantic team of scientists led by the London-based Institute of Cancer Research (ICR) has made a major step towards the development of such a test. They identified 63 new genetic variants that increase the risk of prostate cancer. By combining those variants with 100 others that had previously been identified as culprits in prostate cancer, they were able to identify men who are six times more likely to develop the disease because of inherited risk, according to a statement.
The researchers, who were partly funded by the National Institutes of Health (NIH), analyzed DNA from 80,000 men with prostate cancer and 61,000 healthy men. They used a type of gene-analysis technology called OncoArray to scrutinize single-letter changes in the DNA of those men. The study included five scientists from the University of Southern California's Keck School of Medicine.
Each of the 63 newly discovered variants barely influenced prostate-cancer risk on its own, but when several of them were inherited together, the danger rose dramatically. For example, the men in the top 10% of the population with inherited variants faced a one in four chance of developing prostate cancer, according to the statement. The study was published in Nature Genetics.
The researchers were surprised to discover that several of the variants related to prostate cancer were in genes that come into play when cells communicate with the immune system. They believe that finding warrants further investigation, because it could inform efforts to develop immunotherapy treatments for prostate cancer. The study only involved white males, but parallel research is underway in other ethnic groups, said Christopher A. Haiman, professor of preventive medicine at the Keck School of Medicine, in a statement.
Indeed, understanding the genetic underpinnings of prostate cancer could boost treatment strategies, particularly in patients whose tumors are resistant to standard treatments. Last month, for example, a team at the University of California, San Francisco, published research focused on two genetic mutations that have been found in half of patients with treatment-resistant prostate cancer. After discovering that aggressive prostate tumors with both mutations produce too much of a growth-promoting protein, they found a compound that could block that protein.
The ICR-led team believes the ability to identify men who are born with genetic variants that increase the risk of prostate cancer could change how physicians screen healthy men for the disease—potentially catching more prostate tumors in their earliest stages, when they are easier to treat. The information from the study might also be useful for developing prevention strategies, they believe.
"We are on the cusp of moving from theory to practice,” said Paul Workman, professor and CEO of the ICR, in the statement, “from explaining how genetics affects prostate cancer risk, to testing for genetic risk and attempting to prevent the disease.”