Bruce Ponder

Bruce Ponder is Li Ka Shing Professor of Oncology at Cambridge and Director of the Cancer Research UK Cambridge Research Institute, and Co-Director of the Hutchison/MRC Research Centre and of the Strangeways Research Laboratory for Genetic Epidemiology. His interests are in inherited susceptibility to cancer, and in the effective application of basic science to cancer treatment, detection and prevention.

He trained in medicine in London and then did a PhD at ICRF in molecular biology. He trained in medical oncology at the Dana Farber Cancer Institute, Harvard Medical School. Subsequently during a Cancer Research Campaign Career Development Award he developed new methods to reveal the mosaicism in tissues of chimeric mice, with the aim of understanding the normal clonal cellular organisation  of tissues, and how this breaks down in cancer. He also provided some of the first data on the stem cell organisation of the new intestinal crypt, showing (among  other things) that intestinal crypts are clones.

During this time he developed a clinical interest in cancer genetics, establishing one of the first clinics for familial cancer. His laboratory identified ret as the gene for MEN 2 syndrome, and he was the first Chair of the International Consortium which ultimately underpinned the finding of the BRCA1 and BRCA2 genes. His research efforts are now focussed on common genetic variation and susceptibility to cancer, and his group recently completed the first successful genome scan  for  breast cancer, which has identified 7 new loci for predisposition. They have also demonstrated the potential application of this information to targeting screening and prevention.

Over the past 10 years Bruce Ponder has led the development of a new laboratory and clinical centre for cancer research in Cambridge, culminating in 2007 with the opening of the new CRUK Cambridge Research Institute. He was knighted in 2008 for services to medicine.

Common genetic variants, risk, and applications in cancer

The era of genome-wide association studies has  promised the discovery of many new common genetic variants that influence cancer susceptibility. The hope is that these will uncover new mechanisms in cancer development, and also allow prediction of individual risk which can be used to target  screening and prevention to the individuals  who can benefit most.

The common variants that have been discovered to date each confer a small increment of risk to the individual, which will in most cases not be of practical clinical value. However, a ‘risk profile’ constructed from a combination of risk alleles may provide a stronger discrimination, both for individual decisions about medical interventions, and for the classification of groups of individuals within the population, for example to set risk/benefit criteria for entry into national screening programmes.

Although conferring only small increases in individual risk, common variants account for a substantial fraction of cases of cancer within the population. Targetting the mechanisms by which these variants cause susceptibility is therefore in principle an approach to cancer prevention – analogous to the use of statins in cardiovascular disease. The problem is that this implies preventative treatment of a large fraction of the population for public health benefit but only small individual benefit.

I will discuss the issues around risk estimation and the application of the results, using breast cancer as an example.