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Mystery Solved? This Is How Diabetes Increases Cancer Risk…

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Diabetes, dubbed the silent killer, is known to increase the risk for several cancers, including colon cancer, postmenopausal breast cancer, pancreatic cancer and liver cancer to name a few. This correlation has always been puzzling for researchers and they have been working to solve this medical mystery. Earlier it was suspected that hormone dysregulation, chronic inflammation and insulin resistance may be behind the increased cancer risk in diabetics.

Researchers, led by John Termini of the City of Hope, a research and treatment center for cancer and diabetes, have come out with a new theory for the increased cancer risk associated with diabetes.

According to the researchers, when blood sugar levels are high, the DNA suffers more damage and gets repaired less often compared to when blood sugar is at a normal, healthy level, thereby increasing one's cancer risk.

As part of the research, in tissue culture and rodent models of diabetes, Termini and colleagues looked for a specific type of damage in the form of chemically modified DNA bases, known as adducts. In diabetic models, they found that a DNA adduct, called N2-(1-carboxyethyl)-2'-deoxyguanosine, or CEdG, occurred more frequently than in normal cells or mice. They also found that high glucose levels interfered with the cells' process for fixing the damaged DNA.

"Exposure to high glucose levels leads to both DNA adducts and the suppression of their repair, which in combination could cause genome instability and cancer," according to Termini.

In a clinical study, the researchers found that two specific proteins, mTORC1 and HIF1a, were showing less activity in diabetes, and this perhaps could be the reason as to why the damaged DNA was not getting repaired.

According to Termini, many drugs that stimulate HIF1a or mTORC1 are already there on the market. Metformin, a common diabetes medicine, also stimulates DNA repair. Termini is now planning to test Metformin, in combination with drugs that specifically stabilize HIF1a or mTORC1 in diabetic mammals. If this proves to be effective in reducing cancer risk in diabetic animals, the test can be performed in humans, he said. However, the only available method now to lower the risk of cancer in diabetes patients is to control their blood sugar, Termini pointed out.

Roughly 425 million people in the age group of 20-79 years worldwide were having diabetes in 2017, according to data published by the International Diabetes Federation. This number is estimated to reach 629 million by 2045.

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