Blood cell gene fault linked to breast and ovarian cancer

In collaboration with the Press Association

Scientists have linked a rare genetic fault in the immune system to an increased risk of breast and ovarian cancers.

The research from a team at The Institute of Cancer Research suggests an entirely new way tumours develop.

The lead researcher on the study, Professor Nazneen Rahman, said it was one of her lab's "most interesting and exciting discoveries".

According to the study, published in the journal Nature, women with faults in a gene called PPM1D in their blood cells were 20 per cent more likely to develop breast or ovarian cancer.

That is twice the average breast cancer risk and more than 10 times the ovarian cancer risk of women in the general population.

The discovery could have implications for future genetic testing and targeted prevention, especially in the case of ovarian cancer.

Dr Emma Smith, Cancer Research UK's senior science information officer said: "This exciting discovery could help doctors identify women at higher risk of developing breast and ovarian cancer in the future.

"This may have a particular impact on ovarian cancer, which is often diagnosed at a late stage.

"Understanding the genetic mistakes that drive these cancers may also lead to new ways to treat these diseases."

The researchers speculate that they have uncovered a new cancer-causing process, since the PPM1D gene appears to operate differently to other genes known to increase the risk of breast and ovarian cancer, such as BRCA1 and BRCA2.

The team found that changes in PPM1D were not inherited and rather than being present in every cell - as in most inherited cancer-causing genes - they were only present in immune cells known as lymphocytes.

Even more surprisingly, the PPM1D gene was not altered in women's cancer cells, nor in their normal breast or ovarian cells, the study discovered.

The changes make the PPM1D gene overactive, reducing the action of a gene called TP53, one of the most frequently altered genes in cancer cells.

The ICR's Professor Nazneen Rahman, who led the study, said: "This is one of our most interesting and exciting discoveries. At every stage the results were different from the accepted theories.

"We don't yet know exactly how PPM1D mutations are linked to breast and ovarian cancer, but this finding is stimulating radical new thoughts about the way genes and cancer can be related."

Professor Rahman said the findings could also help inform women's decisions about future medical treatments.

A woman might, for example, consider keyhole surgery to remove her ovaries after completing her family if she knew she had PPM1D changes and had a one in five chance of developing ovarian cancer.

The study was funded by Cancer Research UK, the ICR, the Wellcome Trust and Breakthrough Breast Cancer.

Researchers analysed 507 genes involved in DNA repair in 1,150 women with breast or ovarian cancer, identifying PPM1D gene changes in five women.

They then sequenced the PPM1D gene in 7,781 women with breast or ovarian cancer and 5,861 people from the general population.

25 of the women with cancer had faults in PPM1D, compared with only one in the general population, a highly statistically significant difference, the researchers said.

Copyright Press Association 2012


  • Ruark E. et al. (2012). Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer, Nature, DOI: