Caspase-12 is found in around 20% of people of African descent, but was entirely lost from all other ethnicities around 60,000 years ago. "It's a mystery why only African populations retained this enzyme," says Dr. Maya Saleh, a medical scientist in the Critical Care Division at the MUHC and assistant professor in the Department of Medicine at McGill University. "It's possible that in Africa the protein could once have had a protective function fighting autoimmune diseases or perhaps parasites, like malaria; today caspase-12 provides no benefit to those who carry it, and often leaves the body more vulnerable to life-threatening infections and sepsis ('septic shock'). "Only by investigating the mechanisms by which caspase-12 works can we hope to inhibit its destructive effects," says Dr. Saleh.

Dr. Saleh and a research team from Merck and the La Jolla Institute for Allergy and Immunology in San Diego conducted laboratory experiments using mice deficient in the caspase-12 gene. "We discovered that caspase-12 blocks the body's inflammatory response to infection by blocking the activity of another useful enzyme," says Dr. Saleh. "It's kind of like the bad leading the good astray." Dr. Saleh's discovery is a major step forward and will allow researchers to develop treatments that may help strengthen the immune system of those people unfortunate enough to have the caspase-12 gene product.

mcgill

Dr. Tutt and his collaborators, Dr. Mackay, of University College London, and Max Parmar, of the Medical Research Council clinical trials unit, are supported by Breakthrough Breast Cancer and Cancer Research UK.

All cancers are caused by copying mistakes in DNA, which cause cells to start dividing uncontrollably, and BRCA1 and BRCA2 are essential to repairing these errors.

Two copies of each gene are inherited, one from each parent, but when one copy is mutated the other has no back-up, making cancers more likely to develop.

The resulting tumours have no working copy of the DNA repair gene at all, while the healthy tissue around them has one normal copy.

This makes them more vulnerable to Carboplatin.

The research may one day lead to improved quality of life and survival for women with this rare but important form of genetic breast cancer.

Dr. Mackay says the trial is unique because it is the first to treat a specific genetic population of breast cancer patients.

He hopes this will mean an improved quality of life and survival for women with this rare but significant form of genetic breast cancer.

There is currently there is no specially tailored chemotherapy treatment for women with faulty BRCA genes who have recurrent breast cancer, and such patients receive standard chemotherapy which is not always effective and can have unpleasant side effects.

Patients interested in signing up for the trial need to have a known fault in either BRCA1 or BRCA2, have a cancer that has spread beyond the breast and lymph glands and for which surgery is not suitable.

They must also not had any chemotherapy since the cancer spread.