Hereditary Colorectal Cancer: eMedicine Gastroenterology

Background

Hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal-dominant syndrome, accounts for 2-5% of all colorectal carcinomas. Colorectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) presents at an earlier age than in the general population and is characterized by an increased risk of other cancers, such as endometrial cancer and, to a lesser extent, cancers of the ovary, stomach, small intestine, hepatobiliary tract, pancreas, upper urinary tract, prostrate, brain, and skin.



Table 1. Seven different genes are known to be associated with HNPCC, 
and all of them are involved with DNA mismatch repair, identified with
the frequencies below.

Mismatch Excision Repaired MMR	Chromosome Location	Frequency of HNPCC Cases
MSH2	2p16	45-50%
MLH1	3p22.3/A>	20%
MSH6	2p16	10%
PMS2	7p22.1	1%
PMS1	2q32.2	Rare
MSH3	5q14.1	Rare
EXO1	1q43	Rare
Other genes not yet discovered Table 2. Incidence of different types of cancers between individuals with Lynch syndrome and those in the general population. Table Type of Cancer General Population Risk (by age 70 y) Lynch Syndrome Risk (by age 70 y)   Endometrial 1.5% 40-50% Ovarian 1% 9-12% Upper Urinary Tract Less than 1% 4-10% Stomach Less than 1% 13% (higher in Asians) Small Bowel Less than 1% 1-3% Brain Less than 1% 1-4% Biliary Tract Less than 1% 1-5%		20-25%