Poor diet increases cancer risk: Scientists uncover missing link

ISLAMABAD, April 18 (Online): Poor nutritionTrusted Source is associated with many health conditions, among them obesity, heart disease, type 2 diabetes, and cancers, including those of the breast, uterus, and large intestine. High intakes of sodium, saturated fats, and sugars can increase the risk of chronic conditions like heart disease and type 2 diabetes, but what links diet and cancer is less clear.
Although many foods are said to be associated with increased or decreased cancer risk, according to the National Cancer InstituteTrusted Source, no studies have yet shown that any dietary component directly causes or protects against cancer.

Now, a study from the National University of Singapore, published in CellTrusted Source, has discovered a mechanism that may help to explain why poor diet increases cancer risk.
In cell studies, the researchers found that methylglyoxal, which is produced when cells break down glucose to release energy, can inhibit genes that protect against cancer. They suggest that poor diet leads to higher levels of methylglyoxal, increasing the likelihood of cancer.

“This study suggests a potential correlation between high levels of methylglyoxal, a metabolic by-product, and a genetic mutation pattern seen in some cancers. It is an interesting area to explore further, but we need further lab research and clinical testing to conclusively establish if methylglyoxal levels are directly linked to cancer risk.”
— Dr. Tayyaba Jiwani, science engagement manager at Cancer Research UK, who was not involved in the study, speaking to Medical News Today.

Breast cancer gene increases effect of methylglyoxal
Methylglyoxal is a by-productTrusted Source of the metabolism of glucose, proteins and lipids. It is a reactive small molecule that can disrupt cell function, so is broken down by enzymes into less harmful substances. However, if too much methylglyoxal is produced, the study suggests, the excess can then damage DNATrusted Source.
The researchers first investigated the effect of methylglyoxal in cells from people who had inherited a copy of a mutated gene — BRCA2 — that increases the risk of breast and ovarian cancers.
They discovered that methylglyoxal temporarily disabled tumor suppression by BRCA2, which could increase the likelihood of cancer developing.

Prof. Ashok Venkitaraman, corresponding author, NUS Centre for Cancer Research, National University of Singapore, told Medical News Today:
“[M]ethylglyoxal triggers the destruction of BRCA2 protein, reducing its levels in cells. (It doesn’t prevent expression of the BRCA2 gene.) This effect is temporary, but can last long enough to inhibit the tumor-preventing function of BRCA2.”
Methylglyoxal damaged DNA in cells that had the mutated form of the BRCA2 gene. Repeated exposure to methylglyoxal increased the level of damage to the DNA.

“It is well documented that some individuals are at a high risk of developing breast, ovarian, pancreatic or other cancers because they inherit a faulty copy of the cancer-preventing gene — BRCA2 — from their parents,” Venkitaraman said.
“Our recent findings show that cells from such individuals are particularly sensitive to the effects of methylglyoxal, which is a chemical produced when our cells break down glucose to create energy. We find that methylglyoxal inhibits the tumor-preventing function of BRCA2, eventually causing faults in our DNA that are early warning signs of cancer development,” he added.

Similar effects seen without gene
“The study revealed that even individuals without a genetic predisposition might still face an increased cancer risk if they present with elevated methylglyoxal levels. This scenario is commonly observed in those with diabetes or pre-diabetes, conditions often linked with obesity or suboptimal dietary and lifestyle habits.”
— Kelsey Costa, MS, RDN, registered dietitian nutritionist and founder of Dietitian Insights, who was not involved in the study, speaking to Medical News Today.

Costa explained how methylglyoxal might have this effect:
“Methylglyoxal produces a group of complex compounds known as advanced glycation end-products (AGEs), which accumulate in the body and contribute to various health conditions, including diabetes and obesity. These AGEs have been linked to increased oxidative stress and inflammation, both of which are critical factors in cancer development.”
High levels of methylglyoxal are common in people with prediabetes and diabetes, and can also result from obesity and eating a poor diet.

“Diabetes is a condition where the body has trouble controlling blood sugar (glucose) levels, so people with prediabetes/diabetes have higher than normal levels of glucose. Some of this excess glucose is broken down by glycolysis, in turn elevating methylglyoxal,” Venkitaraman told MNT, explaining also that:
“Poor diets rich in sugar or refined carbohydrates are known to cause blood glucose levels to spike.”

What the findings might mean
Venkitaraman cautioned that, as their work was carried out in cells, not patients, it would be premature to give specific advice to reduce cancer risk on the basis of their findings. However, he explained how their work might influence thinking about genes and cancer:
“Our work also revises a longstanding theory about certain cancer-preventing genes. This theory — called the Knudson’s ‘two-hit’ paradigmTrusted Source — was first formulated in 1971 and proposed that these genes must be inactivated permanently in our cells before cancer can arise.”

“Our latest findings show that methylglyoxal can temporarily inactivate such cancer-preventing genes, suggesting that repeated episodes of poor diet or uncontrolled diabetes can ‘add up’ over time to increase cancer risk,” he said.
Dr. Jiwani cautioned that more research was needed to confirm the effects of methylglyoxal:
“The study shows that exposing cancer cells in the lab to high levels of methylglyoxal can transiently deplete the tumor-suppressor protein BRCA2, increasing the risk of DNA damage. But this alone doesn’t prove that these cells will go on to become cancerous. Additional research is needed to see if these same effects occur in the more complex contexts of our tissues, organs, and bodies, where metabolic reactions and by-products are intricately regulated.”

More evidence that diet affects cancer risk
Costa told MNT that this research provides another reason to try and follow a healthy diet:
“Diets rich in unhealthy processed foods, red meats, added sugars, and refined grains, like the typical Western diet, may lead to an increase in methylglyoxal due to metabolic dysfunction, posing a risk for various diseases, including obesity, cardiovascular diseases, diabetes, and an elevated risk of cancer.”

“As is often the case, the best way to reduce methylglyoxal production and maintain metabolic, microbiome, and overall health is to eat a balanced, plant-forward diet that is rich in dietary fiber and bioactive compounds, with a focus on whole and minimally processed foods,” she advised.
One diet often advocated for improving health is the Mediterranean diet and, Costa said, and there is now evidence that it might reduce methylglyoxal levels.

“In fact, in a recent study,” she said, “following a Mediterranean diet was linked to lower methylglyoxal levels in the bloodstream, which appeared to help maintain kidney health among individuals with type 2 diabetes and coronary heart disease.”