Dr Graeme Suthers and Dr Hamish Scott
Child Health Research Institute, Institute of Medical and veterinary Science, Walter and Eliza Hall Institute
Australian Familial Hematological Cancer Study
Dr Graeme Suthers and Dr Hamish Scott's research team
It is now generally accepted that 5-10% of most cancers in society are caused by mutations in highly penetrant genes and another 10–15% may still show highly significant 'familial' clustering due to low-penetrance genes, gene–environment interactions, or both.
Unlike solid tumors, hematological cancers are not in the envious position where a litany of cancer causing germ-line mutations have been identified. Is this simply as we have not looked hard enough? We know from the lessons of the molecular genetics of solid tumours such as breast and colon cancer that the identification of genes responsible for relatively rare cases of familial hematological malignancies will afford valuable insight into the mechanism underlying the more common sporadic occurrences.
While there are no specific medicine developed that act against the family cancer genes identified so far, there are already significant clinical benefits. For example, with an inherited form of colon cancer, hereditary nonpolyposis colon cancer or HNPCC, it is possible to predict with nearly 90% accuracy the risk of the disease in patients with direct germ-line mutations. With early detection, these colon cancers are curable in 90% of patients.
We have strong preliminary evidence of Australian families that have genetic predispositions to develop these hematological cancers. With the growing recognition that these families exist, we plan to identify and collect samples from these families to be used in identification of the genes responsible for predisposition to hematological cancers.
The genes responsible for these hematological cancer predisposition disorders are also likely to be mutated in sporadic hematopoietic malignancies. Familial predispositions provide a unique chance to identify these genes. These genes may act as predictive markers for disease progression or be a targets for therapeutic protocols.
