GENETICS IN RENAL CANCER

Cancer is a genetic disease, due to the accumulation of mutations in genes (oncogenes and tumour suppressor genes that control the balance between cell birth and cell death. In some cases these are germline and inherited, while the large majority are somatic mutations. Interestingly, in most cases, such as in inherited kidney cancer syndromes, the same genes cause both inherited and sporadic (non-inherited) forms of cancer. As the molecular basis of disease continues to be elucidated, familial cancer syndromes, which consist of a range of neoplastic and non-neoplastic features, are emerging. The usual pathway of referral to a genetics clinic or familial cancer centre is via either a surgeon or an oncologist, when high-risk features that suggest a possible hereditary basis for the presenting cancer are recognized. Traditionally, these high-risk features include more than two family members with similar types of cancer over two or more generations, a young age of onset, and more than one synchronous or metachronous tumour. These features are effective in ascertaining a substantial proportion of families with hereditary cancer. However, there are a range of familial cancer syndromes that are not easily detected and can remain undiagnosed when history and examination are not extended to include cancer in other sites and non-malignant features. Identification of predisposition to develop cancer 1 is particularly important in the case of inherited kidney cancer syndromes, as it provides individuals and their families with the opportunity to undertake early surveillance for malignant complications that might in time be shown to undertake nephron-sparing surgery and to improve outcomes. Kidney cancer with diverse aggressiveness has been associated with germline mutations of one of the following genes: VHL, MET, FH, BHD or TSC. The genetic mechanism, histopathology and clinical history of kidney cancer associated with each of the above gene mutation will be discussed.