Critical step towards DNA test to detect early bowel cancer

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Researchers from Cancer Research UK’s Cambridge Research Institute analysed 261 tumour samples taken from patients who had either benign bowel polyps or had developed bowel cancer.

They revealed that the DNA methylation patterns of two genes called SFRP2 and IGF2 identified and distinguished between tumours and benign polyps - with an accuracy of more than 90 per cent.

DNA methylation is essential for life. In healthy cells a compound called a methyl group is tagged to DNA where it acts as a ‘red light’, preventing certain genes from producing proteins. But this process can go wrong in cancer cells. DNA methylation can also contribute to the cause and development of cancer by blocking important protective genes.

Lead author, Dr Ashraf Ibrahim, at Cancer Research UK’s Cambridge Research Institute at the University of Cambridge, said: “The molecular signals, which tell genes whether to make proteins or not, can become jumbled in cancer cells. We’ve identified several places where this signal becomes damaged and shown this is linked to bowel cancer development.

“The majority of bowel cancers develop from benign polyps that turn cancerous - and this crucial research deepens our understanding of the molecular changes behind this development. This first step in detecting molecular ‘flags’ for bowel cancer, could, one day, lead to a simple test to search DNA for the early signs of the disease.”

The scientists also measured levels of an enzyme called DNMT3B, which helps add methyl groups to DNA. They found levels of the enzyme in tumour samples increased from lower amounts present at the polyp stage to higher levels in bowel cancer. The increase in enzyme levels corresponded with the increased amount of DNA methylation - and provided an explanation for these changes.

Bowel cancer is the third most common cancer in the UK. About 38,610 people are diagnosed with the cancer each year in the UK - more than 100 people every day.

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “This important research opens the way to improve detection of bowel cancer as early as possible when it is easier to treat successfully.

“Our research has played an important part in the excellent progress being made in the treatment of bowel cancer – the five-year survival rates for bowel cancer have doubled over the last 40 years.

“We’ve come a long way in improving screening and developing better treatments – our scientists have been involved in testing many drugs that are used to treat bowel cancer and they’ve had a key role in pinning down the genetic causes of the disease.

“But, there is still more to be done. Research like this is vital in our goal to develop the best methods to detect, monitor and treat cancer and improve survival.”

Reference

1. Ibrahim A, Arends M, et al. Sequential DNA methylation changes are associated with DNMT3B overexpression in colorectal neoplastic progression. Gut 2011. doi: 10.1136/gut.2010.223602

klíčová slova: DNA methylation, DNA test, bowel polyps, bowel cancer