Researchers from 300 institutions around the world combined forces to discover 72 previously unknown gene mutations that lead to the development of breast cancer. Two studies describing their work published Monday in the journals Nature and Nature Genetics.

The teams found that 65 of the newly identified genetic variants are common among women with breast cancer.

The remaining seven mutations predispose women to developing a type of breast cancer known as estrogen-receptor-negative breast cancer, which doesn't respond to hormonal therapies, such as the drug tamoxifen.

The new discoveries add to previous research bringing the total number of known variants associated with breast cancer to nearly 180.

Beyond BRCA1 and BRCA2

The international team of 550 researchers across six continents, known as the OncoArray Consortium, included professor Doug Easton of the University of Cambridge, who led the investigation.

"Essentially, we used blood samples from a very large number of women (nearly 300,000), about half of whom had had breast cancer," Easton explained in an email. Next, the researchers used the DNA from the samples to look for genetic mutations.

"Think of a gene as a very long strand of DNA," said Dr. Otis Brawley, chief medical officer of the American Cancer Society , who was not involved in the research. DNA is made up of nucleic acids, and when a nucleic acid is incorrectly placed along the strand, this is referred to as a genetic mutation, noted Brawley.

Take BRCA1 and BRCA2, two well-known genes that confer a high risk of breast cancer when they contain mutations.

There are 125,950 base pairs in the BRCA 1 mutation, noted Brawley.

"Think of it as a 125,950 letter word," said Brawley. "A mutation is a misspelling such that the gene cannot code the proper protein." A gene that cannot code the proper protein leads to disease.

According to the National Cancer Institute , 55% to 65% of women who inherit a BRCA1 mutation and around 45% of women who inherit a BRCA2 mutation will develop breast cancer by age 70.

However, the BRCA1 and BRCA2 risk mutations, which are present in less than 1% of women, explain only a fraction of all inherited breast cancers.

The consortium came together, then, to discover the other causes of breast cancer susceptibility -- the additional genetic mutations that can lead to this form of cancer.

Finding the other mutations

The researchers measured DNA at over 10 million sites across the genome, said professor Peter Kraft of Harvard T.H. Chan School of Public Health, a study author.

"At each of these sites, we asked whether the DNA sequence in women with breast cancer was different than that in women without," said Kraft. "Because our study was so large, we could detect subtle differences between these two groups of women and be sure these differences were not due to chance."

According to Jacques Simard, a study author and professor and researcher at Université Laval, Quebec City, the newly discovered mutations only slightly -- by anywhere from 5% to 10% -- increase a woman's risk of developing breast cancer.

But even though, individually, these mutations don't have as big as an effect as BRCA1 and BRCA2 defects, there are many of them, so their "overall contribution is larger," said Easton. An individual woman, then, may have two or more of these common smaller risk gene mutations, and so her risk for developing breast cancer increases due to their combined effects.

Kraft noted that "taken together, these risk variants may identify a small proportion of women who are at 3-times increased risk of breast cancer." Women found to have a number of these smaller risk genetic mutations, then, would likely benefit from earlier mammography screening.

Simard agreed, noting that it may be time to "adapt" breast cancer screening guidelines based on this information instead of basing mammography guidelines on age alone. By doing so, Simard said, "we will detect a higher number of breast cancers."

Quantifying cancer risk

Brawley described the new research as "not earth-shattering." It is "most important for us nerds," he said, but less so for the general public.

These types of studies help experts identify mutations that "help us quantify the risk," said Brawley. "It helps us figure out that a non-patient, often a relative of a cancer patient, is at risk and helps us quantify that risk." Normal lifetime risk of breast cancer is 12.5% for women in the US, said Brawley.

Lisa Schlager, vice president of community affairs & public policy for the nonprofit FORCE (Facing Our Risk of Cancer Empowered), said past studies and evidence indicate that about 10% of breast cancers are hereditary.

"This new information may mean that that estimate is low," said Schlager.

It is important for patients to know whether their cancer is due to an inherited genetic mutation because they may be at increased risk of other cancers or their treatment recommendations may differ based on that fact, said Schlager.

"And their family members may be affected with the same mutation," said Schlager.

Enabling personalized medicine

For the promise of personalized medicine to be realized, our government and health system need to "embrace the ability to use genetic information to tailor health care by providing affordable access to the needed screening and preventive interventions," said Schlager. As it stands now, men with BRCA mutations as well as some women may not be covered for screening by their insurance in the US.

Brawley said "this type of genome wide screening has and is being used to identify genes that are associated with increased risk of a number of diseases, including diabetes, Alzheimer's disease, stroke and heart disease."

"The same methodology can be used for other cancers," said Easton. The screening method used by the consortium, the OncoArray, was designed to be used in many other cancer types, including prostate, ovary, colorectal and lung cancer, he said.

Simard added that the cost of the genetic screen is "quite cheap," at less than $50 per individual. "We can use just a blood sample or saliva sample. It's not difficult to obtain the material for a genetic analysis," he added.

Kraft said it was important to keep in mind that the study was conducted primarily among women of European ancestry.

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"For sure we have missed some variants associated with cancers that are common in some non-European populations but rare in Europeans," said Kraft. To find these, cancer genetic studies in Africans, African Americans, Latinas, Chinese and other populations are ongoing, he added.

Easton commented that most of the newly identified variants "are in regions of the genome that regulate nearby genes." These may someday serve as targets for new therapies or drugs to cure the disease.

In the end, the most important lesson here is the fact that this research has been a collaborative effort, said Simard.

"Scientists are not in competition against each other," he said. "We are really working together to expedite and to accelerate the discovery."