A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: Meeting Highlights and Bethesda Guidelines

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is a distinct autosomal dominant syndrome accounting for approximately 5%–6% of the total colorectal cancer burden with clinical and pathologic features caused by defective mismatch repair genes ( 1 ). Germline mutations in hMSH2, hMLH1, hPMS1, hPMS2, and MSH6/GTBP have been identified in affected individuals ( 2 , 3 ). HNPCC is characterized by early-onset colorectal cancer (median age at diagnosis 45 years); right-sided predominance; excess synchronous and metachronous colorectal neoplasms; and an increased incidence of extracolonic neoplasms, including endometrial, small-bowel, gastric, renal pelvis and ureter, and ovarian tumors and skin lesions, such as sebaceous adenomas, carcinomas, and keratoacanthomas ( 4–10 ).