Natural 'defence' gene reveals how oestrogen fuels cancer

CANCER RESEARCH UK scientists have shown for the first time how a natural 'defence' gene involved in fighting infections such as common colds, can be triggered by hormones to ignite and drive cancers like breast, ovarian, and possibly prostate cancer. Their findings are published in the Journal of Experimental Medicine.

A team of researchers at Clare Hall Laboratories, in Cancer Research UK's London Research Institute, have shown that the female hormone oestrogen is able activate the AID protein. There is strong evidence that abnormally high levels of the AID protein can mutate genes responsible for cell growth - which could lead to cancer. This discovery could explain how hormones fuel some cancers and provide a lead to future research on prevention and treatments.

The AID protein is typically involved in normal healthy immune responses. It enables the body to make thousands of different antibodies needed to fight infections.

Lead author Dr Svend Petersen-Mahrt, head of the London Research Institute's DNA Editing laboratory said: "We know that mutations in some of our genes can cause cells to grow in an uncontrolled manner - leading to cancer. But it was not fully understood how hormones like oestrogen fuel those mutations in some forms of the disease - although we knew there was a strong connection. This research shows that AID is could be the missing link."

The international team of scientists, discovered this link by treating cells with the hormone oestrogen in the laboratory and analysed the effect of the hormones on the level of DNA mutations.

Dr Petersen-Mahrt continued: "Knowing how AID connects oestrogen to cancer is an important discovery. There are around 45,000 new cases of breast cancer in the UK each year and three quarters of these are thought to be fuelled by the hormone. But all women produce oestrogen and most of them will not develop a hormone induced cancer, so we now need to find out what other genetic and environmental factors trigger the disease in some cases and not others."

Dr Lesley Walker, director of cancer information at Cancer Research UK said: "This finding is very important because scientists have long wrestled with the task of explaining the link between oestrogen and cancer even though we knew it was core to the fight against the disease. The link is particularly pertinent to women receiving increased amounts of oestrogen for prolonged periods of time - during Hormone Replacement Therapy (HRT) for instance - because it can increase their risk of developing cancer.

"Knowing how the mutations are fuelled could help us find new ways to stop the oestrogen from activating the AID gene - potentially treating and possibly even preventing cancer. But AID is also very an important defence against infections and does not by itself do any harm. So we would need to be very careful about interfering with the way the gene works."

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