Here's why diabetes increases the risk of cancer

Here's why diabetes increases the risk of cancer
© Getty Images

Diabetes is linked to increased cancer risk, raising questions as to whether the prevalence of cancer will increase in the next few decades. 

About one in nine people in the United States has type 2 diabetes, according to the Centers for Disease Control and Prevention. The number of people living with diabetes continues to rise even as the incidence rate for the disease is leveling off. Obesity is a significant risk factor for diabetes, and childhood obesity is on the rise. In fact, nearly 25 percent of 12- to 19-year-olds are classified as obese. All signs point to more people living with diabetes and its associated complications.

One of the lesser-known complications is an increased risk for cancer of the liver, pancreas, endometrium, kidney and breast. A recent study suggests that overall cancer risk in women with diabetes may be about 6 percent higher compared to men’s disease risk. The exact reasons for this link are unclear, but excess circulating insulin, estrogen and pro-inflammatory hormones from fatty tissue are thought to play a significant role. These biological events can promote cell mutation and tumor progression.

ADVERTISEMENT

My research suggests that there are additional reasons why people with diabetes are more susceptible to cancer. Keep in mind that DNA damage could lead to the development of tumors.

For the past 12 years, the Termini Lab at City of Hope has been investigating the relationship between diabetes-induced DNA damage and cancer. This could be the Trojan horse that makes our bodies more vulnerable to developing cancer. We found that elevated blood sugar levels, called hyperglycemia, can damage DNA. It can chemically modify DNA bases — genetic coding information. These modifications induce mutations — the kind that is associated with some cancers.

We were the first laboratory to measure this base damage and describe their mutations in human cells. Our study in animal models of type 2 diabetes and a more recent clinical study in humans confirmed that these DNA modifications are significantly more prevalent in both mouse models of type 2 diabetes and in humans.

The second and perhaps more significant damage is in the form of DNA strand breaks that result from unrepaired base modifications. These breaks can cause DNA fragments to rearrange; genes are shuffled in unexpected ways that could lead to abnormal cellular functions.

To be fair, a typical cell falls victim to thousands of “attacks” every day as a result of normal metabolic reactions and environmental exposures. A DNA “damage control team” scours our genome to patch up the injuries. The problem arises when the damage control team is put on the sidelines by damage to something called nucleotide excision repair (NER). When this happens, it brings about a rare condition called xeroderma pigmentosum, which increases human susceptibility to DNA damage and significantly elevates cancer risk.

ADVERTISEMENT

We examined whether elevated glucose could be a factor that causes cancer by mimicking the high-glucose environment found in people with diabetes. We measured the expression of genes and proteins in cell and mouse models and compared the results to a controlled group. We found significant changes in NER and metabolic pathways. Notably, elevated glucose significantly reduced the repair of DNA damage. In fact, the low repair rate was comparable to cells derived from a patient with xeroderma pigmentosum.

Increased genomic instability (DNA damage, mutations and DNA strand breaks) should be considered a complication of diabetes. Efforts should be directed toward addressing these complications therapeutically. 

The bottom line is more people are living with diabetes, which is linked to cancer. Worldwide obesity has nearly tripled since 1975, according to the World Health Organization. The fact that type 2 diabetes can result from obesity paints a world where cancer could close the gap on heart disease, the No. 1 cause of death globally. It was recently reported that cancer now tops heart disease as the leading cause of death among middle-aged adults in some countries. 

Others and I are trying to stop that from happening. My lab is investigating whether drugs approved by the U.S. Food and Drug Administration can stimulate DNA repair. We are testing our hypothesis in diabetic animal models with the hope that, eventually, therapies can be developed to minimize cancer susceptibility in people with diabetes.

We are up to the difficult task. In 1978 City of Hope conducted research that led to the development of synthetic human insulin. Its diabetes efforts are led by, Arthur Riggs, Ph.D., the man who co-created that technology. Additionally, City of Hope, with support from The Wanek Family Project for Type 1 Diabetes, is committed to designing a cure for patients coping with type 1 diabetes.

For now, there are things you can do to lower your risk of diabetes and, hence, cancer. Though some people are genetically more prone to get diabetes, lifestyle choices can lower your risk of type 2 diabetes. Here are some life hacks: Reduce your sugar intake, make healthier food choices that are low in fat and include a lot of fiber. Lastly, don’t forget to exercise regularly.

John Termini, Ph.D., has been investigating the relationship between diabetes-induced DNA damage and its role in enhanced cancer susceptibility for more than 12 years. He is a professor in the Department of Molecular Medicine at City of Hope, a research and treatment center for cancer and diabetes.