SINGAPORE: The National University of Singapore (NUS) announced in a press release late last week that a research team has discovered new findings that could explain how a poor diet or uncontrolled diabetes could, over time, increase the risk of cancer.

The university said on April 12 that “the insights gained from this study hold promise for advancing cancer prevention strategies aimed at promoting healthy ageing.”

The groundbreaking study was led by Professor Ashok Venkitaraman and carried out by scientists from the Cancer Science Institute of Singapore (CSI Singapore) at NUS and NUS Centre for Cancer Research (N2CR) under the Yong Loo Lin School of Medicine, with colleagues from the Agency for Science, Technology and Research (A*STAR).

“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,” said Prof Venkitaraman, the Director of CSI Singapore.

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Patients who inherited a faulty version of the cancer gene BRCA2 from their parents were studied by the research team. This gene causes them to have a high risk of developing breast or ovarian cancers.

Cells from the patients showed that they were especially sensitive to the effects of the chemical methylglyoxal, which is produced when a body’s cells break down glucose to create energy.

“The study showed that this chemical can cause faults in our DNA that are early warning signs of cancer development,” NUS said.

Individuals who’ve not inherited a faulty version of BRCA2 but may have higher-than-normal levels of methylglyoxal, including pre-diabetes or diabetes patients, may show the same warning signs of a higher risk of developing cancer.

Diabetes and pre-diabetes are connected with a poor diet or obesity. Prof Venkitaraman further explained that the chemical may be detected easily through a blood test for HbA1C.

However, the even better news is that high methylglyoxal levels can usually be controlled with a good diet and medication, which allows proactive measures against cancer cells from even beginning to develop.

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“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 Dr Li Ren Kong, a Lee Kuan Yew Fellow from N2CR and the study’s first author.

The team’s research also suggests a novel mechanism for tumour formation, revising a long-held theory on specific genes that prevent cancer.

The theory, Knudson’s ‘two-hit’ paradigm, dates back to 1971 and proposes that genes need to be permanently inactivated in cells before cancer arises.

However, the team from NUS has discovered that methylglyoxal can temporarily inactivate genes that prevent cancer. This suggests that repeatedly having a poor diet or uncontrolled diabetes may “add up” as time goes by to raise the risk of cancer.

“This new knowledge is likely to be influential in changing the direction of future research in this area,” NUS wrote, adding that significant findings from the team were published on one of the most influential scientific journals in biomedical research, Cell, on 11 April 2024.

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The university also said that the next step in the team’s research involves studies to understand if “metabolic disorders such as diabetes or poor diets, affect cancer risk in Singapore and other Asian countries.”  /TISG

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