How The Body's Immune System Can Trigger Cancer

How The Body's Immune System Can Trigger Cancer

A key weapon in the body's immune system armoury may play a major role in triggering cancer, new research suggests.

Scientists were surprised to find that the family of virus-fighting proteins produce gene defects linked to several cancers.

The discovery was especially unexpected because one of the main functions of the molecules is to protect DNA from attack by viruses.

The body's immune system could trigger cancer

The proteins, known as APOBEC cytidine deaminases, cause clusters of mutations that can outnumber all others associated with cancer, say the researchers.

They were found to account for more than two-thirds of some bladder, cervical, breast, head and neck, and lung tumour mutations.

All cancers are ultimately the result of mistakes in the genetic code that remain uncorrected. These can have a number of causes, including toxic chemicals and radiation.

The new evidence, from a study of a million mutations in 2,680 cancer samples, suggests APOBEC proteins may be one important trigger.

In some samples nearly 70% of mutations could be traced to the molecules.

The scientists wrote in the journal Nature Genetics: "Here we have developed a single detailed hypothesis - that APOBEC cytidine deaminases are a significant source of mutagenesis in human cancer genomes."

Lead researcher Dr Dmitry Gordenin, from the US National Institute of Environmental Health Sciences, said the proteins may have caused "many mutations" across the human genome, or genetic code book.

It was possible APOBEC-triggered mutations and viral infection were linked, the scientists added.

Story continues below...

Cervical and head and neck cancers, both strongly associated with human papillomavirus (HPV) infection, had especially large numbers of APOBEC mutations.

The discovery could lead to new ways to avoid cancer, the researchers believe.

Co-author Dr Steven Roberts, a member of the same NIEA team, said: "We hope that determining the environment link to these mutations will lead to viable cancer prevention strategies."

A second study published in Nature Genetics shows that a genetic abnormality linked to cancer is associated with type 2 diabetes.

People with type 2 diabetes were already known to have a higher risk of some cancers, especially lymphoma and leukaemia.

The research showed a connection with mutations called clonal mosaic events (CMEs) which result in extra or missing copies of large chunks of DNA.

People with CMEs have a 10-fold increased risk of blood cancers.

The study showed that CMEs were four times more common in people with type 2 diabetes than in the general population.

"This finding may partly explain why people with type 2 diabetes are more likely to get blood cancers," said study leader Professor Philippe Froguel, from Imperial College London. "It could have profound clinical implications."

It may be useful for doctors to test for CMEs in patients with diabetes to identify those at highest risk of cancer, said the researchers.