Study finds high concentrations of glucose cause genetic mutation in pancreatic cells, which can eventually lead to pancreatic cancer.
Pancreatic cancer is one of the toughest cancer diseases. One reason is due to its non-specific low-key symptoms at early onset such as upper abdominal pain, back pain, lack of appetite, fatigue, or weight loss. None of these symptoms are considered a clear indication.
When pancreatic cancer is eventually diagnosed, around 80 per cent of the cases are metastasis, and only 20 per cent are treatable with surgery. Despite this, 80 per cent of successfully treated patients would still develop metastasis of pancreatic cancer.
Only when the mechanism of pancreatic cancer is understood, can an effective therapeutic be developed.
So, researchers from Academia Sinica in Taiwan have published their findings in Cell Metabolism, where they pinpoint the cause and effect of pancreatic cancer, and shed light on the prevention and treatment of the disease.
KRAS is a gene known to enhance cell growth, it is also reputable in causing cancer cell growth when it is defective.
The researchers found 94 per cent of KRAS defects were reported among pancreatic ductal adenocarcinoma (PDAC) cancer cases, which is an aggressive type of pancreatic cancer. Survival rates of PDAC are three to six months after diagnosis.
Their study observed normal pancreatic tissues from pancreatic cancer patients with and without diabetes. Normal pancreatic tissues from diabetic patients have significantly higher KRAS gene mutation than non-diabetic tissue samples.
Mice tests also showed if fed with high sugar high fat diet for a long period of time, their blood sugar will tend to increase. However, after examining the pancreas, colon, intestine, liver, lung and kidney tissues, only the tissues from the pancreas appeared to have DNA damage and KRAS gene mutation.
So what is exactly causing the KRAS gene mutation in pancreatic cells?
Since the pancreas is responsible for metabolism, the team figured the digestion process may play a role in the damage of DNA.
They conducted a series of cell experiments treated with high concentrations of glucose, glutamine (amino acids), and palmitic acid (saturated fatty acids) separately and results showed high concentrations of glucose caused a genetic mutation in the pancreatic cells.
There was also a significant decrease of dNTP (deoxy-ribonucleoside triphosphate) within the cells when there are increased levels of glucose inside the cells. dNTP is a type of nucleotide transformed from glucose intakes inside our body and is important for DNA replication and repair.
When excess amount of glucose is absorbed into the pancreatic cells, a glycosylation process would be activated. This post-translational modification specifically compromised the ribonucleotide reductase (RNR) activity, leading to deficiency in dNTP pools.
Due to the decrease in dNTP pools, the genomic process of pancreatic cells might cause replication stress to increase mutations including oncogenic KRAS mutation.
Once the gene had a mutation, defected pancreatic cells are unleashed and grew quickly, resulting in pancreatic cancer.
Their study also indicates that, although the excessive glucose triggers the glycosylation and blocks the self-repair mechanism, such scenario only happens to pancreatic cells, not the lung cancer cells, nor the colon cancer cells, although these two diseases have a strong correlation with diabetes.
This study confirmed the fact that too much glucose adds the burden to the frontline metabolism actions in pancreas and causes cancer. The bottom line – protect the pancreas, avoid high sugar diets! [APBN]