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Sir Bruce A. J. Ponder, FRCP, FMedSci, FRS
Emeritus Professor of Oncology
University of Cambridge, United Kingdom
Seeking to improve risk assessment for hereditary breast cancers.
A mathematical system is employed to discern how alterations in breast cancer risk genes interact to influence risk.
Results from these studies may improve our understanding of inherited risk of breast cancer and inform prevention strategies.
Rare mutations in the BRCA genes cause greatly increased risks of breast and ovarian cancers in some families. All our genes have some degree of normal variation between individuals. Sometimes these variations are good; sometimes they carry a disadvantage, which for some genes may include a very small extra risk of breast cancer. We all inherit a different set of gene variants from our parents – rather like a hand of cards.
Some people get a ‘good’ hand in respect of breast cancer, some a ‘bad’ hand. The result is a wide range of risk across the population.
Although the risks attached to any one gene are small, the difference between the worst and the best ‘hand’ of genes can be quite large. Over 100 such genes have now been identified, but working out how they act is difficult, and has been tackled laboriously one gene at a time – which misses the point that they act together.
Dr. Ponder and his team have developed new ways to understand how the known genes combine to alter risk. They have now “mapped” the genes that are linked to risk for breast cancer into gene networks. Many of these genes lie in the same part of the network involved in the actions of female (estrogenic) hormones.
Dr. Ponder's studies have shown that the level of estrogen activity is a balance between the effects of opposing groups of genes. In the coming year, the group will include new genes in a faster and simpler analysis, to explore other possible mechanisms of risk.
Results from these studies may improve our understanding of mechanisms of inherited risk of breast cancer, and thus of ways of prevention.
Bruce Ponder is Emeritus Professor of Oncology at Cambridge, former Head of Oncology and Director of the Cancer Centre, and was the Founding Director of the Cancer Research UK Cambridge Research Institute. He established one of the first clinics for familial cancer and contributed to gene discovery and genetic epidemiology in thyroid, breast and ovarian cancer. His focus is now on common genetic variation and cancer susceptibility. Over the past 10 years he has led the development of a new laboratory and clinical center for cancer research in Cambridge, culminating in 2007 with the opening of the new CRUK Cambridge Research Institute. From 2010-2014 he served as President of the British Association for Cancer Research, and was knighted in 2008 for "services to medicine".