Hereditary nonpolyposis colorectal carcinoma (HNPCC): clinical application of molecular diagnostic testing

An increased risk of colorectal cancer amongst close relatives of afflicted patients has been recognized for some time. Hereditary nonpolyposis colorectal cancer (HNPCC) represents an extreme example of this risk, in which single-gene inheritance predisposes relatives of affected family members. Approaches to surveillance and management of subjects at greater or lesser heritable risk have been evolving in the past two decades, but these efforts have suffered due to our inability to better characterize and quantify that risk. Recent discovery of susceptibility loci that are linked to disease in HNPCC has already begun to refine our understanding of the pathogenesis of the disease. At a clinical level, these advances now offer an improved ability to recognize carriers of the condition. Speculation is provided as to the probable utility of genetic testing in groups with varying strengths of colorectal cancer familiality. Notions of how positive and negative tests might be applied to surveillance and treatment are explored.