Scientists at the Johns Hopkins Kimmel Cancer Center and the Bloomberg Kimmel Institute for Cancer Immunotherapy have identified a surprising link between oral health and breast cancer. Their research shows that bacteria commonly associated with periodontal disease can promote breast cancer development, accelerate tumor growth, and facilitate its spread by damaging DNA and changing the behavior of cancer cells.
Published in Cell communication and signalingresearch focuses on Fusobacterium nucleatuma microorganism that has previously been linked to colorectal and other cancers. Researchers have found that this bacteria can enter the bloodstream and colonize breast tissue, where it can cause inflammation and early cell changes associated with cancer. In animal models of human breast cancer, the presence of this bacterium accelerated tumor growth and increased the spread of cancer cells from the breast to the lungs.
“The important point is that this oral microbe can be present in breast tissue, and there is a link between this pathogen and breast cancer,” Professor Sharma said, adding that his team’s research looked at thousands of patients and was inspired by a number of smaller studies linking periodontal disease and breast cancer.
“We wanted to dig deeper and see if we could uncover any underlying connections,” says Dr. Sheetal Parida, lead author and Sharma’s research associate.
DNA damage and tumor-promoting changes
Experiments using mouse models and human breast cancer cells revealed how this bacterium affects tissues. when F. nucleatum When introduced directly into the breast ducts, it caused metaplastic and hyperplastic lesions, non-cancerous changes in which cells grow excessively or transition to another type. These changes were accompanied by increased inflammation, DNA damage, and cell proliferation. Once the bacteria entered the bloodstream, it significantly accelerated the growth and spread of existing tumors.
The research team also uncovered important biological processes behind these effects. exposure to F. nucleatum The cell’s DNA is damaged and error-prone repair systems are activated. One of these, nonhomologous end joining, quickly reconnects broken DNA strands but can introduce mutations. Even brief exposure to this bacterium increased levels of a protein called PKcs, which was associated with cancer cell migration, invasion, increased stem-like traits, and resistance to chemotherapy.
Higher risk of BRCA1 mutated cells
Certain cells appeared to be particularly sensitive. Epithelial cells (the cells that line the breast ducts) and breast cancer cells with BRCA1 mutations were more susceptible. These BRCA1 mutant cells had increased levels of surface sugars (Gal-GalNAc) that help bacteria attach to and enter cells. As a result, these cells absorbed more F. nucleatum And it persists over time, even across multiple cell generations, reinforcing DNA damage and cancer-promoting effects.
“Our findings reveal an association between oral microbiota and breast cancer risk and progression, particularly in genetically susceptible individuals,” Sharma said. “On their own, nothing happens. These results suggest that, together with multiple risk factors, F. nucleatum may act as an environmental factor, working with inherited BRCA1 mutations to promote breast cancer and tumor aggressiveness.”
Impact on oral health and cancer risk
The researchers emphasize that further research is needed to understand how these findings apply to patient care. Future research will investigate whether maintaining good oral health can play a role in reducing breast cancer risk.
In addition to Sharma, the research team included Sheetal Parida, Deeptashree Nandi, Deepak Verma, Minyan Yi, Ashutosh Yendi, Jessica Queen, Kathleen Gabrielson, and Cynthia Sears.
This research was supported by the Breast Cancer Research Foundation, the Congressional Medical Research Program (Department of Defense Breast Cancer Research Program Grants BC191572 and BC210668), the John Fetting Breast Cancer Prevention Fund, and the Bloomberg Kimmel Institute for Cancer Immunotherapy.
