Lower Cancer Incidence in Amsterdam-I Criteria Families Without Mismatch Repair Deficiency

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by significantly increased risks for colon cancer as well as for cancers of the endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, and ovary.1,2 Most studies have not reported increased risks for lung, breast, or prostate cancers in HNPCC kindreds. Many experts currently use the term HNPCC synonymously with a hereditary DNA mismatch repair (MMR) gene deficiency, and studies of cancer risks in the syndrome have generally focused on families with MMR deficiency. Based on fairly consistent cancer risks in studies of various designs, clinical screening guidelines have been proposed, focusing especially on screening for cancers of the colon and endometrium.3-6 However, in the broader clinical realm and in some current medical literature, the term HNPCC continues to be based on pedigree criteria, typically the strict Amsterdam I criteria (AC-I),7 which have 3 elements: (1) there are at least 3 relatives with histologically verified colorectal cancer (1 a first-degree relative of the other 2), and familial adenomatous polyposis should be excluded; (2) at least 2 successive generations should be affected; and (3) 1 of the relatives’ colorectal cancers should be diagnosed before age 50 years.