Study Unlocks New Insight about Breast Cancer Risk

A new study led by a researcher at New York Institute of Technology provides insight that could change how scientists and clinicians understand genetic predisposition to breast cancer, a condition that affects one in eight U.S. women in her lifetime.  

Understanding a patient’s genetic predisposition to breast cancer can help clinicians predict the likelihood of disease development and select the most effective treatment options. While 27 percent of all breast cancers may be caused by inherited genetic mutations, not all mutations have the same impact. For example, BRCA gene mutations, which are known to directly increase breast cancer risk, are found in only ten percent of breast cancer patients. Yet, these patients can be up to six times more likely to develop breast cancer. On the other hand, some studies suggest that having many commonly occurring variations in DNA building blocks can impact one’s chances of developing breast cancer.  

Now, a new study published in Life Science Alliance by William Letsou, Ph.D., assistant professor of biological sciences at New York Institute of Technology, suggests another scenario: having a certain, rare combination of common variants could highly increase breast cancer risk.  

Letsou and his co-authors, including researchers from St. Jude Children’s Research Hospital, the University of Minnesota, and the University of Alberta (Canada), developed a new algorithm to analyze the genetic makeup of 9,000 women with breast cancer. Within this group, the researchers singled out women carrying the same variant of a single-nucleotide polymorphism (SNP), a variation of one DNA base in a gene sequence, that was previously linked to breast cancer risk.  

The researchers discovered that the women with this SNP could be further categorized into subgroups based on other nearby variants they had inherited. Although these inheritance patterns were rare, the team noted that they occurred more frequently in those diagnosed with breast cancer—in fact, four times as often. These findings suggest that having a certain combination of common variants could significantly increase one’s breast cancer risk.   

“To date, the role of computational biology has been to uncover how thousands of common polymorphisms additively impact disease risk. Basically, the more variants you carry, the higher your risk of developing certain cancers. However, our new computational method shows that having a specific combination of common variants may be enough to increase disease risk,” says Letsou.  

The researchers hope that their method will uncover additional rare combinations of SNPs in other genes, which may, in the long term, allow clinicians to better assess breast cancer risk and inform targeted therapies for different subsets of patients.