Tooth decay may make colon cancer more aggressive, according to a new study.The findings add to the growing swell of research that show oral health may be linked to much, much more than just the look and smell of our teeth.
In the last few years, research has shown dental plaque is linked to heart health, neurological disorders, and tumor growth. And now Dr. Yiping Han, a pioneer in this emerging field, has found another connection: people with bowel cancer may be harder to treat if they have poor oral health.
Dr. Han, of Columbia University’s College of Dental Medicine, said the finding helps explain why some cases advance far more quickly than others. Ultimately, it suggests we may be blinkering our vision by focusing on the tumor’s mutations alone, rather than other factors.
“Mutations are just part of the story,” Han said. “Other factors, including microbes, can also play a role.”The research team worked out how F. nucleatum – a common oral bacteria often implicated in tooth decay – accelerates the growth of colon cancer.
A third of colorectal cancers are associated with a common oral bacterium called F. nucleatum. Those cases are often the most aggressive, but nobody knew why.In a previous study, Dr Han’s research team discovered that the bacterium makes a molecule called FadA adhesin, triggering a signaling pathway in colon cells that has been implicated in several cancers.
They also found that FadA adhesin only stimulates the growth of cancerous cells, not healthy cells.Dr Han said: “We needed to find out why F. nucleatum only seemed to interact with the cancerous cells.”In the new study, the researchers found in cell cultures that non-cancerous colon cells lack a protein, called Annexin A1, which stimulates cancer growth.They then confirmed both in vitro and later in mice that disabling Annexin A1 prevented F. nucleatum from binding to the cancer cells, slowing their growth.
The researchers also discovered that F. nucleatum increases production of Annexin A1, attracting more of the bacteria.Han said: “We identified a positive feedback loop that worsens the cancer’s progression.“We propose a two-hit model, where genetic mutations are the first hit. F. nucleatum serves as the second hit, accelerating the cancer signaling pathway and speeding tumour growth.”
The researchers then looked at an RNA-sequencing data set, available through the National Center for Biotechnology Information of 466 patients with primary colon cancer.
Their findings, published online in the journal EMBO Reports, showed that patients with increased Annexin A1 expression had a worse prognosis, regardless of the cancer grade and stage, age, or sex.The research team is now looking for ways to develop Annexin A1 as a biomarker for more aggressive cancers, and as a potential target for developing new treatments for bowel and other types of cancer.