Researchers find new genetic markers for breast cancer risk

0

What is your true risk of developing breast cancer in the next 10 years or perhaps over a lifetime? 

A major international research collaboration aimed at tracing the genetic fingerprints of breast cancer has doubled the number of possible culprits involved in the most common cancer affecting women worldwide. The discovery is expected to help pinpoint who is most at risk of developing breast cancer.

The group involving Canadian scientists discovered 72 new genetic markers that contribute to the risk of developing breast cancer, more than doubling the number to nearly 180 genetic variations.

The initiative by the OncoArray Consortium involved two studies by 550 researchers from about 300 institutions on six continents. They pooled and analyzed the genetic data of 275,000 women, and 146,000 of them received a breast cancer diagnosis.

Researchers isolated genetic areas that are specifically associated with hormone-dependent breast cancers and others associated with hormone-independent breast cancer that do not respond to therapies like tamoxifen.

Researchers believe these discoveries will lead to a predictive cancer test for women, as well as changes in screening based on personal risks of developing breast cancer. 

Published online in the journals Nature and Nature Genetics, the studies show distinct biological characteristics for two different types of cancers that develop differently, explained Jacques Simard, head of the Research Centre of the University Hospital of Laval University, holder of the Canada Research Chair in Oncogenetics and one of the principal authors. 

Breast cancer is the result of complex interactions between a large number of genetic variations and our environment, Simard said. For some women, the hereditary component — a combination of rare variations in such genes as BRCA1 and BRCA2 — results in a very high risk of developing the disease, and increases the risk for ovarian cancer as well. But the mutation is rare, affecting about 15 per cent of all breast cancers. 

However, the newly identified genetic markers are very common, although their individual risks are low, Simard said. But when combined, the risks are multiplied, he said. A woman with more variants will have a greater risk of developing the disease, he added.

“We have 180 variations, but we don’t know which ones a woman will have,” Simard said. “It’s like playing poker. You just don’t know which card you have, and some cards have more weight than others.”

However, Simard and his colleagues say a single test — a mathematical-risk assessment — based on genetic profiling (that takes into account the new markers) in addition to lifestyle factors can identify women who are predisposed to cancer. 

“This is a major application of this discovery,” Simard said.

However, risk assessment testing is currently not available.

“But the good news is that we have developed the tool and we have a team in place,” said Simard, who with his colleagues is hoping for a research grant to fund a genetic profiling and risk-prediction pilot study in Quebec and Ontario.

Personalized screening would go a long way to improve cancer prevention, reduce over-testing and over-diagnosis as well as false positives, Simard added, while increasing survival and quality of life. For example, one in five cancers are detected in women under age 50.

“These women would benefit from early and more intense testing,” Simard said, yet the current recommendation for the general population is for women to get a mammogram as of age 50. 

But based on a risk assessment, some women would be eligible for the more sensitive magnetic resonance imaging (MRI) testing and at an earlier age, Simard said. 

“We are estimating that 25 per cent of all cancer will be diagnosed in a minority of women who are at higher risk. This is major,” he said. “On the other hand, we will be able to identify women at substantially lower risk” who could start mammogram testing later and have them at a lower frequency.

Researchers said the studies also led to a greater understanding of the biological mechanism underlying breast cancer.

Most of the variants were not found within genes, but in areas of the genome that regulate the activity of nearby genes, Simard said.

“It’s like traffic lights on street corners regulating traffic,” he said. “The variations were not located there by chance. We now have a better understanding of how certain genes are regulated, and that may lead to new targets for new therapies.”

Research funding was provided by Genome Canada, the Canadian Institutes of Health Research, Genome Que?bec, the Quebec Breast Cancer Foundation, Cancer Research U.K. and the U.S. National Cancer Institute, among others.

cfidelman@postmedia.com

Source Link

Share.