A team of researchers from the National University of Singapore (NUS) has made a significant breakthrough in understanding how poor diets contribute to an increased risk of cancer and other common diseases, such as diabetes. The findings of this study promise to enhance strategies for cancer prevention and promote healthier ageing.
Professor Ashok Venkitaraman spearheaded the research at the Cancer Science Institute of Singapore (CSI Singapore) and the NUS Centre for Cancer Research (N2CR) at the Yong Loo Lin School of Medicine. The team collaborated closely with colleagues from the Agency for Science, Technology and Research (A*STAR).
Professor Venkitaraman, the Director of CSI Singapore, highlighted the complexity of cancer’s causation, which involves genetic factors and environmental influences like diet, physical activity, and pollution. He stressed the importance of clarifying these interactions to devise effective preventative measures contributing to sustained health.
Central to their research was the study of methylglyoxal, a byproduct of glucose breakdown in cells, implicated in diabetes, obesity, and poor dietary habits. This chemical was found to be particularly damaging to the DNA of patients with an inherited risk of breast or ovarian cancers linked to a defective BRCA2 gene. Such damage serves as an early indicator of potential cancer development.
Further investigations revealed that individuals without the genetic defect but with elevated methylglyoxal levels—such as those suffering from diabetes or pre-diabetes associated with poor diet—also showed signs of increased cancer risk. Professor Venkataraman explained that detecting high methylglyoxal levels through a simple blood test, like the HbA1C, could be a marker for cancer risk, paving the way for preventative treatments through medication and dietary adjustments.
Dr Li Ren Kong, a Lee Kuan Yew Fellow at N2CR and the study’s first author mentioned that their initial goal was to explore risk factors in genetically predisposed families. Still, they uncovered a crucial link between energy metabolism and cancer development. This underscores the importance of diet and weight management in cancer risk reduction.
The research also challenged a long-standing theory in cancer genetics, known as Knudson’s ‘two-hit’ hypothesis, which posits that cancer-preventing genes need to be permanently disabled for cancer to emerge. The team’s findings suggest that temporary inactivation of these genes by compounds like methylglyoxal, mainly through repeated poor dietary choices or unmanaged diabetes, could cumulatively heighten cancer risk over time. These insights could significantly redirect future cancer research.
Their groundbreaking work, published in the prestigious journal Cell on 11 April 2024, has set the stage for subsequent studies. The team plans to explore further how metabolic disorders affect cancer risks in different populations, particularly in Singapore and other Asian contexts.
Looking ahead, the researchers are eager to delve deeper into the mechanisms they’ve uncovered between metabolism, diet, and cancer. Their goal is to develop more effective strategies to prevent or delay the onset of cancer, potentially transforming the landscape of cancer research and prevention.
More information: Li Ren Kong et al, A glycolytic metabolite bypasses “two-hit” tumor suppression by BRCA2, Cell. DOI: 10.1016/j.cell.2024.03.006
Journal information: Cell Provided by National University of Singapore
