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Linking Human Genetics with Molecular Medicine: Will Hereditary Renal Cancer Play a Major Role?

An inherited or familial predisposition to form kidney tumors represents less than 4% of all renal malignancies. However, hereditary renal cancer (HRC) syndromes offer important opportunities for gene discovery and function. Basic and clinical HRC investigation often provides unique insight into regulation of cell growth, cell proliferation, tumor invasion and metastasis. The genetics, biochemistry and physiology of renal tumorigenesis has been directly impacted and significantly expanded by HRC research over the last ten years. Mutations have been identified in several genes tightly linked to increased risk for development of renal cancer. Inheritance of these mutated genes causes specific hereditary syndromes often associated with clinically significant non-renal manifestations. Molecular and biochemical alterations of most HRC gene products are also detected in sporadic renal cancer emphasizing the importance of HRC gene function in non-hereditary carcinogenesis. Despite these important molecular findings, the clinical contribution of HRC research has generally been limited to genetic screening and prognostic assessment. HRC patients and their physicians continue to face difficult decisions regarding cancer control and quality of life despite advances in minimally invasive surgical and radiological techniques. The ultimate challenge for clinicians and scientists will be translation of molecular and genetic research into clinical tools that impact diagnosis, treatment and prevention. This bench to bedside report describes the diagnosis, genetics, pathophysiology and current cancer treatment options available for HRC syndromes.