Researchers from the Murdoch Children’s Research Institute (MCRI) have found that genetic techniques could be used to ‘switch on’ proteins that may protect against stomach cancer.
The research investigated Helicobacter (H.) pylori, a bacteria that can cause chronic inflammation, potentially leading to stomach cancer.
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H. pylori infects the stomach of roughly half the world’s population. Acquired during early childhood, it triggers inflammation of the stomach lining which, according to the researchers, is harmless in around 85 per cent of infected individuals.
However, in the remaining 15 per cent of people, chronic inflammation caused by H. pylori infection has more serious consequences, causing peptic ulcers and stomach cancer.
Current preventative therapy for stomach cancer is based on antibiotic eradication of H. pylori. However, an increased global prevalence of antibiotic resistant H. pylori strains has resulted in current treatment strategies becoming less effective, leading to efforts to find new ways to combat stomach cancer.
Led by Dr Treve Menheniott and Professor Andy Giraud, researchers investigated the interaction of Gastrokine-2 (GKN2) — a protein normally present at high levels in healthy human stomach — and H. pylori in vulnerable people.
They found that GKN2 is ‘switched off’ in people with stomach cancer, and suggest that it might function to protect against H. pylori infection and related stomach cancer risk.
To investigate this possibility, the team used specialist genetic tools to ‘switch off’ GKN2 in mice. These ‘GKN2-deficient’ mice, when infected with the stomach cancer-causing H. pylori bacteria, developed more severe stomach inflammation, accelerated precancerous disease and tumours, than mice with normal GKN2 levels.
The team showed that when normal levels of GKN2 were restored in a stomach cancer mouse model, tumour growth was significantly inhibited.
According to Dr Menheniott, who is also an Honorary Fellow at the University of Melbourne, findings identify GKN2 as a critical suppressor of inflammation-driven stomach cancer.
“Restoring GKN2 protein to normal levels in advanced H. pylori infections or stomach tumours may help to slow or prevent progression of this often fatal disease,” he said. “As such, GKN2 may have novel therapeutic value in 15 per cent of infected individuals for whom antibiotic treatment fails or in people with irreversible precancerous stomach lesions.”
Professor Andy Giraud, said that the research could help protect those at risk of stomach cancer by inhibiting tumour growth.
“While the survival rate for people with stomach cancer is only around 27 per cent, these findings are really exciting for us because stomach cancer can be treated much more efficiently if diagnosed early,” said Professor Giraud.
According to the Cancer Council, stomach cancer affects nearly twice as many men as women. The risk of being diagnosed with stomach cancer by age 85 is one in 63 for men compared to one in 136 for women.
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