A previously unknown mechanism that inactivates genes that suppress tumor formation helps explain why cancer risk increases associated with unhealthy eating habits or uncontrolled metabolic conditions such as diabetes.
Researchers in Singapore and the UK used mouse models, human tissue and lab-grown human breast organoids to show that changes in glucose metabolism can temporarily disable genes that protect us from tumors. They discovered that it may help cancer grow. BRCA2.
“These findings increase awareness of the impact of diet and weight management in managing cancer risk.” To tell The lead author of the new study is cancer pharmacologist Lee Leng Kong from the Cancer Science Institute of Singapore (CSI Singapore).
“We began our study with the aim of understanding the factors that increase the risk of cancer-prone families, but ultimately discovered deeper mechanisms linking essential energy expenditure pathways and cancer development. I decided to do it.”
The discovery also calls into question long-established theories about genes that protect against cancer. Knudson’s “two-hit” paradigmFirst proposed in 1971, both copies tumor suppressor genes It must be permanently inactivated within our cells before cancer can develop.
A recent study found that one of the two cells has a mutation. BRCA2 gene Involved in various cancers.Interestingly, mouse and human cells with this mutation Does not show the usual signs of genetic instability Both copies of the gene are found in mutated cells.
With a mouse, BRCA2 to be influenced Doesn’t seem to cause any major problems in organ development or DNA repair Present in most organizations. However, cells with this mutation appear to be more vulnerable to stresses such as: Exposure to environmental toxins Some drugs, such as formaldehyde and acetaldehyde, can reduce BRCA2 protein levels and cause functional problems.
“We still don’t fully understand how these environmental factors increase cancer risk, but understanding the relationship is essential to taking preventive measures to stay healthy longer. ” To tell Ashok Venkitaraman, oncologist and cancer researcher at CSI Singapore;
The researchers first studied people who had inherited one defective copy. BRCA2. They found that these people’s cells were more sensitive. Methylglyoxal (MGO), produced when cells break down glucose for energy during the process of glycolysis.
Glycolysis produces more than 90% of MGO within cells. enzyme pair Usually kept at minimal levels. If MGO levels cannot be maintained, high MGO levels can lead to the production of harmful compounds that damage DNA and proteins. In conditions such as diabetes, where hyperglycemia increases his MGO levels, these harmful compounds contribute to complications of the disease.
The researchers found that MGO can temporarily override the tumor suppressor function of the BRCA2 protein, resulting in mutations associated with cancer development. This effect can be seen not only in non-cancerous cells, but also in patient-derived tissue samples, some cases of human breast cancer, and mouse models of pancreatic cancer.
as BRCA2 Alleles are not permanently inactivated, and the functional form of the protein they produce may return to normal levels later. However, cells repeatedly exposed to MGO may continue to accumulate cancer-causing mutations each time production of the existing BRCA2 protein fails.
Overall, this suggests that changes in glucose metabolism may interfere with BRCA2 function via MGO and contribute to cancer development and progression.
These results were obtained from clinical tests and small human tissue samples, and researchers are working on a larger study to examine possible links between dietary factors, diabetes, and other metabolic disorders. They say further research is needed using large-scale clinical studies and animal models.
MGO can temporarily take away the BRCA2 protein’s ability to repair DNA, so even in people with two functional copies, a poor diet or uncontrolled diabetes can lead to cancer over time. It makes sense that it could increase the risk of BRCA2 gene. This new information could lead to strategies for cancer prevention and early detection.
“Methylglyoxal is easily detected in blood tests for HbA1C and could potentially be used as a marker,” Venkitaraman said. To tell.
“Additionally, high methylglyoxal levels can usually be controlled with medication and a proper diet, paving the way to preventing the development of cancer.”
This study cell.
