Professor Ashok Venkitaraman, Director of CSI Singapore led this ground-breaking study explains that “Cancer is caused by the interaction between our genes and factors in our environment, such as diet, exercise, and pollution. How such environmental factors increase cancer risk is not yet very clear, but it is vital to understand the connection if we are to take preventive measures that help us stay healthy longer.”
First the researchers studied patients who were at high risk of developing ovarian or breast cancers because they inherited a faulty copy of the cancer gene BRCA2 from their parents, demonstrating that cells from these patients were particularly sensitive to the effects of methylglyoxal. Methylglyoxal is a chemical that is produced when our cells break down glucose to create energy, and the researchers showed that this chemical causes faults in our DNA that are early warning signs for the development of cancer.
The researcher suggests that those who have not inherited the faulty gene could also experience higher than normal levels of methylglyoxal, such as those with prediabetes or diabetes which is connected with poor diet or obesity and can accumulate similar warning signs indicating a higher risk of developing cancer.
“Our research suggests that patients with high methylglyoxal levels may have higher cancer risk. Methylglyoxal can be easily detected by a blood test for HbA1C, which could potentially be used as a marker. Furthermore, high methylglyoxal levels can usually be controlled with medicines and a good diet, creating avenues for proactive measures against the initiation of cancer,” said Venkitaraman.
“We started the study aiming to understand what factors elevate risk in families susceptible to cancer, but ended up discovering a deeper mechanism linking an essential energy consumption pathway to cancer development. These findings raise awareness of the impact of diet and weight control in the management of cancer risks,” said first author, Dr Li Ren Kong, Lee Kuan Yew Fellow.
Additionally, this work revised Knudson’s ‘two-hit’ paradigm theory that was first formulated in 1971 about certain cancer preventing genes, which proposes that these genes must be inactivated permanently in our cells before cancer can arise. This work found that methylglyoxal is able to temporarily deactivate cancer preventing genes, suggesting that poor diet or uncontrolled diabetes can increase cancer risk over time.
In the future the team hope to identify new mechanisms underlying the connection between metabolism, diet and cancer that they have discovered to develop more effective approaches to prevent or delay the onset of cancer. They also aim to build on their novel findings with additional studies investigating if metabolic disorders such as poor diets or diabetes affect the risk of cancer in Singapore and other Asian countries.
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