Study uncovers mechanism linking diet, diabetes, and cancer risk

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The study also calls into question a long-standing idea concerning cancer-protective genes. Recent research has discovered that a mutation in one of a cell's two BRCA2 genes is associated with a variety of cancers.

The connection between a poor diet or poorly controlled metabolic conditions such as diabetes and higher cancer risk is partly elucidated by a previously unidentified mechanism that deactivates genes inhibiting tumour formation.

Using mouse models, human tissue, and in vitro-produced human breast organoids, researchers from Singapore and the UK discovered that disruptions in glucose metabolism may promote the growth of cancer by momentarily blocking the BRCA2 gene, which guards against tumours.

Cancer pharmacologist Li Ren Kong of the Cancer Science Institute of Singapore (CSI Singapore), who is the study's primary author, states that "these findings raise awareness of the impact of diet and weight control in the management of cancer risks."

"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," he added.

The study also calls into question a long-standing idea concerning cancer-protective genes. Recent research has discovered that a mutation in one of a cell's two BRCA2 genes is associated with a variety of cancers. Interestingly, mice and human cells with this mutation do not exhibit the typical symptoms of genetic instability observed in cells with both copies of the gene altered.

In mice, having only one copy of BRCA2 impacted does not appear to create significant difficulties with organ development or DNA repair in most tissues. However, cells with this mutation tend to be more prone to stress, such as exposure to environmental pollutants like formaldehyde or acetaldehyde, which can lower BRCA2 protein levels and cause functional issues.

How do disruptions in glucose metabolism affect BRCA2 function?

The researchers initially looked at persons who had inherited one defective copy of BRCA2. They discovered that these people's cells were more susceptible to methylglyoxal (MGO), which is created when cells break down glucose for energy during glycolysis.

The researchers observed that MGO can temporarily block the BRCA2 protein's tumor-suppressing capabilities, causing mutations associated with cancer development. 

Overall, their findings imply that alterations in glucose metabolism can affect BRCA2 function via MGO, leading to cancer genesis and progression. This new knowledge may help to develop cancer prevention or early detection measures.