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Lynch syndrome (hereditary non-polyposis colorectal cancer; HNPCC) is caused by a germ-line mutation in one of the DNA mismatch repair (MMR) genes. Mutations of the MLH1 and MSH2 genes account for 70–90% of cases. Such patients develop colorectal cancer at an early age and have an excess of extra colonic malignancies, including small bowel cancer with a relative risk >100. Knowing whether to screen such families for this rare condition depends on an accurate knowledge of the absolute risk. In this study, 1496 family members with a MMR mutation from 189 families on the Dutch HNPCC registry were examined. The cumulative risk of developing small bowel cancer in MMR mutation carriers is shown in the figure, with a lifetime risk of 4.2%. The specific MMR mutation did not alter the risk nor did gender. The authors conclude that the annual incidence is too small to justify invasive screening techniques such
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