Vera Villanueva

A new Yale study has found that eight out of 10 people at risk of breast cancer, ovarian cancer, prostate cancer, pancreatic cancer and melanoma are not aware of their elevated risk.

In a clinical study of more than 50,000 patients between 2014 and 2016, researchers collaborating in a cross-institutional project involving Yale’s department of genetics discovered that screening the DNA of a large number of individuals could help identify cancer risk. The study was published in the Journal of the American Medical Association on Sept. 21.

“We looked amongst 50,000 patients and found about 270 individuals that had the genetic mutation [that indicated an increased risk of cancer],” said Michael Murray, the study’s senior author and director for clinical operations at Yale’s Center for Genomic Health. “When we asked how many knew about it through their routine health care management, only 18 percent did.”

By participating in the study, 82 percent of the individuals with the genetic mutation learned about their increased cancer risk for the first time. To obtain this information, the researchers performed a technique called exome sequencing — in which only the DNA used to produce proteins is sequenced, rather than every segment of DNA present in an individual’s cell.

“98 or 99 percent of DNA does not code for protein, so that is outside of the exome,” Murray said. “The 1 to 2 percent that does code for proteins is called the exome. We could get most of the information from somebody’s genome that we wanted to look at through just looking at the exome.”

The researchers searched for a variant of the BRCA1 and BRCA2 genes, which have both been heavily studied and implicated in human cancers, especially breast cancer. By detecting the presence of a BRCA1/2 variant through exome sequencing, the researchers were able to identify individuals with a higher risk of cancer.

Co-investigator and physician at Nationwide Children’s Hospital in Columbus Kandamurugu Manickam, who handled most of the study’s day-to-day operations, said that the researchers hope to improve early detection methods and combine the exome-sequencing technique with existing family history screens.

“Even if we took a good family history, a lot of them had family history that we would not think is suspicious,” Kandamurugu said. “Population screening is the way we can get around this.”

Prior to this technique, genetic screening was laborious and costly, according to Murray. Advances in sequencing technology have allowed techniques such as exome sequencing to become more mainstream, providing important and useful information.

“The standard norm has been to do single-gene analysis, and up until about three years ago, it cost $3,000 to have that test done on someone personally,” Murray said.

In the future, the study’s results will need to be replicated, Manickam said, and he and the other researchers hope to better understand the biological mechanism behind these risks. People are also becoming more open to population screening and to the benefits that it provides, he added.

It costs $2,999 to have a genome sequenced by Veritas Genetics at a diagnostic level, according to the company’s website.

Vikram Shaw | vikram.shaw@yale.edu

Alayna Lee | alayna.lee@yale.edu .