A/Prof Alexander Dobrovic
Peter MacCallum Cancer Centre, Department of Pathology
It is possible that some individuals at risk of developing certain cancers can be identified by looking for low level changes in their normal tissues. We propose to examine readily obtainable normal tissues such as blood for inactivation of genes that usually block the progression of cancer in order to identify patients at risk of developing specific cancers. Once these patients are identified, appropriate risk reducing measures such as early screening or dietary intervention can be taken.
How do we identify individuals who are predisposed to cancer?
Up to now the emphasis has been on identifying individuals with a strong familial history or a history of environmental exposure to cancer causing agents such as cigarette smoke. The aim of this study is to investigate whether the same genes that are known to be mutated in hereditary cancer may be inactivated (silenced) by a type of mechanism known as DNA methylation.
DNA methylation of such genes is known to occur in cancers but the novelty of this study is to examine normal tissues for evidence of DNA methylation of the same genes to identify individuals that may be at increased risk of developing breast and gastric cancer. It may then be possible to decrease this risk by dietary or other interventions to reduce this methylation and thereby decrease the risk of developing cancer.
The MGMT gene which repairs a specific type of DNA damage which increases the mutation frequency is frequently silenced in cancer. Using a very sensitive methodology developed by us, it was shown that methylation of the MGMT gene is strongly associated with a DNA sequence variation. This indicates that somatic methylation which can predispose to cancer may in many instances have a genetic origin. This paper was judged important enough to attract an editorial in the same issue of the journal in which the paper appeared.
Cancer Council Research Grant
$99,000 per annum for three years