- Researchers unveil a new theory on why people with diabetes have a higher rate of cancer.
- The team says the DNA in people with diabetes experiences more damage and isn’t repaired as frequently when blood sugar levels are high.
- One cancer expert, however, says this theory is still unproven and more research is needed.
Last year, researchers determined that people with diabetes have a significantly higher risk of cancer than the general population — but why they do was still a mystery.
Recent research has provided a deeper understanding and firmer theory as to what’s happening in a body with diabetes that increases the likelihood of cancer growth.
“It’s been known for a long time that people with diabetes have as much as a 2.5-fold increased risk for certain cancers,” explained John Termini, PhD, a professor of molecular medicine at the City of Hope National Medical Center in California and lead author of a study presented this past weekend at the American Chemical Society Fall 2019 National Meeting & Exposition in San Diego.
Essentially, Termini and his team said they discovered that DNA in a person with diabetes experiences more damage and isn’t repaired as frequently or successfully when blood sugar levels are high compared to a person with normal blood sugar levels.
Earlier theories included:
- excess levels of insulin that stimulate cancer cell growth
- excess body fat that produces higher levels of adipokines, which
promote cancer growth
- excess hormone production that promotes chronic inflammation, which is linked to cancer
Termini added that while these theories may play a role, research has been unable to produce solid evidence to support them. This led him to pursue a different theory focused on DNA damage and blood sugar levels.
Specifically, the research team honed in on a type of DNA damage referred to as “adducts” that develop more frequently in mice with diabetes compared to mice without diabetes.
While a mouse (or person) without diabetes would be generally successful in repairing this type of DNA damage, researchers found that high blood sugar levels directly interfered with the repair process.
Further, two specific proteins — mTORC1 and HIF1α — that play a crucial role in DNA repair were identified as having less activity in people with diabetes.
“We found that if we stabilize HIF1α in a high-glucose environment, we increase DNA repair and reduce DNA damage,” said Termini. “And mTORC1 actually controls HIF1α, so if you stimulate mTORC1, you stimulate HIF1α.”
One expert in the cancer field emphasizes, however, that this research is still a theory.
“This research is showing that chronic exposure to elevated glucose levels significantly increases this adduct. They’re then hypothesizing that it is more likely to cause errors in the DNA,” Dr. Noah D. Kauff, chief of cancer genetics at the Northwell Health Cancer Institute in New York, told Healthline.
“In terms of the exact mechanism, all cancer is ultimately the result of DNA damage because fundamentally the property that all cancers share is that they have developed damage in the critical signal in the DNA,” Kauff explained.
“There’s an error in the critical instruction within the DNA that would normally tell the damaged cells when to stop growing,” he added.
Kauff noted that everyone experiences DNA damage in their body.
“Every time our cells divide, they have to copy our DNA. Every cell has an entire copy of our DNA, which is 3 billion chemical letters, and errors and damage inevitably occur,” he explained.
For a person with diabetes, Kauff says, this research reveals there are two more things that help cancer form.
The first is the likelihood of errors within newly divided cells and the failure to properly repair those errors.
“But Mother Nature is good to us and offers a lot of mechanisms to fix errors,” Kauff said. “Just having increased errors doesn’t necessarily lead to DNA defects. They are still hypothesizing that chronically elevated glucose levels are the reason behind these two contributions to increased cancer growth.”
Termini and his researcher team also found that metformin — one of the most prescribed drugs in the first line of defense in type 2 diabetes treatment — actually stimulates the repair process of damaged DNA.
“We’re looking at testing metformin in combination with drugs that specifically stabilize HIF1α or enhance mTORC1 signaling in diabetic animal models,” explained Termini.
Kauff, however, said there isn’t data yet to support using metformin specifically to prevent cancer.
“It’s another reason to take metformin,” explained Kauff. “But at this time, it certainly shouldn’t be considered a cancer-prevention method directly. Instead, it may play a role in reducing blood sugar levels, which in turn reduces a patient’s risk of cancer.”
The most essential steps any person with type 2 diabetes could take to reduce their cancer risk is to improve their blood sugar levels and lose weight through getting more exercise, improving their diet, quitting smoking, and reducing alcohol intake.
“That sounds like such an easy solution, but it’s extremely difficult for most people to maintain glycemic control,” Termini said. “As the incidence of diabetes continues to rise, the cancer rate will likely increase as well.”