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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Clinical implications of advances in the molecular genetics of colorectal cancer.

AIMS AND BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common occurring hereditary form of colorectal cancer (CRC) where it accounts for as much as 10 percent of the total CRC burden. HNPCC is characterized by an autosomal dominant inherited predisposition to early age of onset (= 44 years) of CRC with proximal predominance (= 70% proximal to the splenic flecture) with an excess of synchronous and metachronous CRC (45% 10 years after initial hemicolectomy or segmental resection as opposed to subtotal colectomy), features which characterize the Lynch syndrome I variant, while the Lynch syndrome II variant of HNPCC shows all of these features, but in addition, there is a marked excess of carcinoma of the endometrium, ovary, small bowel, stomach, pancreas, and transitional cell carcinoma of the ureter and renal pelvis, lesions which are integral to this syndrome. Because of the early onset, we recommend colonoscopy to be initiated at age 25 and repeated every other year through age 35 and then annually thereafter. Women need to undergo endometrial aspiration biopsy at the time of initial colonoscopy. METHODS AND RESULTS: Major advances in the molecular genetics of HNPCC have occurred during the past two years with identification of the hMSH2 gene at chromosome 2p and the hMLH1 gene at chromosome 3p, both of which have been cloned. PMS1 at chromosome 2p and PMS2 2 at chromosome 7q have also been implicated in HNPCC's etiology. CONCLUSIONS: Genetic counseling is mandatory for presymptomatic DNA testing and for delivering information about the patient's germline status. Patients with germline mutations are offered prophylactic subtotal colectomy as an option to continued colonoscopy. It is now important for physicians to take careful cancer family histories so that this disorder can be readily identified, thereby enabling the initiation of highly targeted surveillance and management programs.[1]

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