Study doubles genetic factors linked to cancers

A massive collaboration between cancer researchers at more than 160 institutions worldwide has nearly doubled the number of genetic regions known to be associated with three major cancers: breast, ovarian, and prostate.

Individually, each of the 74 new genetic risk factors identified has very little predictive power, each increasing a person’s cancer risk by a tiny amount. Collectively, however, the results reported in 13 papers published Wednesday represent a major step.

Researchers said using a composite of the risk factors now known for the cancers could conceivably lay the basis for tests that could be used to stratify the population into high- and low-risk groups. Those tests could help determine who is at greatest risk from cancers discovered in 2.5 million people worldwide each year and therefore might benefit from aggressive screening,preventive treatment or lifestyle changes.


For example, Rosalind Eeles, of the Institute of Cancer Research in the United Kingdom, said that if a person’s father had prostate cancer, that individual is typically told he has a 25 percent risk of developing prostate cancer, too. But, she said, examining the 77 genetic regions now associated with the disease could show that person’s lifetime risk is higher -- above 50 percent.

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It remains unclear what people found to be at high risk should do, whether they should they get screened more frequently or at a younger age with mammograms or for a marker of prostate cancer called prostate specific antigen, or take other steps.

“What we don’t know is, if your risk is over 50 percent of getting prostate cancer in your lifetime, we don’t know if we should just PSA screen you, whether we should do a biopsy, whether we should do an MRI scan,” said Eeles, who led one of the papers, published in the journal Nature Genetics. She said that in London, a pilot study has already begun to try and understand better what having any of the newly discovered genetic risk factors reveal about how aggressive the disease is, by comparing genetic profiles with screening results.

Screening has been a contentious topic in the United States over the past few years, as official guidelines for the frequency of mammograms and prostate cancer tests have changed, sparking objections and concerns from patients, disease advocacy groups, and physicians. What has become clear is the need to fine-tune screening, so that those who could benefit the most from it receive it. The US Preventive Services Task Force, which makes recommendations on screening, has so far mainly been trying to write guidelines for the general population.

“The problem was they were trying to make a one-size-fits-all recommendation, and what we all know is that the whole point of cancer risk is it’s not one-size-fits-all,” said Dr. Leif Ellisen, director of breast and ovarian cancer genetics at the Massachusetts General Hospital Cancer Center. For “colon cancer, prostate cancer, breast cancer, we know numerous risk factors in each case -- and the idea there should be a one-size-fits-all approach to screening just doesn’t make sense.”


Boston cancer researchers said one goal of the new, large studies, which analyzed genetic regions in more than 200,000 people, is that they could provide ways to design more effective, individualized prevention and treatment strategies. But they said the public health repercussions of the explosion of new genetic regions, called SNPs, associated with the three cancers is still unknown.

“What is this all going to mean, in terms of to the patient? I’m still not sure yet,” said Dr. Philip Kantoff, chief clinical research officer of Dana-Farber Cancer Institute. “The hope is more educated screening and treatment strategies. The problem with that is you have to add a bunch of these together to get to a point where the risk levels are significant enough.”

So, for example, by the time enough genetic risk areas are added together to increase someone’s lifetime risk of cancer a clinically significant amount, only 1 percent of the population might carry the variants found in all those regions. The open question, Kantoff, said, is whether that is going to be important as a medical screening tool.

Ellisen said the study was very interesting because it began to identify groups of factors that increase risk by an amount that might change how one screened a woman with breast cancer.

“When you’re getting two-, three-, four-fold increased risk, that’s when we begin to recommend different recommendations for screening and prevention in patients,” Ellisen said. “If a woman has a 20 percent lifetime risk [of breast cancer], which is two-fold or more the population average, she could consider an MRI screen in addition to lifetime mammography screening.”


Still, the researchers noted that although the large studies have the promise of dramatically increasing knowledge of the biology of cancer, the known genetic risk factors still account for about a third of the genetic risk for each cancer. That means there is much more to understand, and it is still essential for people to realize they can reduce their chances of getting cancer by reducing environmental and lifestyle exposures.

Carolyn Y. Johnson can be reached at Follow her on Twitter @carolynyjohnson.