Does hereditary nonpolyposis colorectal cancer explain the observed excessrisk of colorectal cancer associated with family history?

Several studies have found an increased risk of colorectal cancer associate d with a family history of colorectal cancer. Some studies, although not al l, have also suggested that family history of colorectal cancer may be a ri sk factor for adenomatous polyps. Hereditary nonpolyposis colorectal cancer is a known genetic syndrome predisposing to colorectal cancer. The hypothe sis of this paper is that the preponderance of the genetic or familial risk for colorectal cancer in the United States is mediated by hereditary nonpo lyposis colorectal cancer. To test this hypothesis, I have incorporated wha t is known about hereditary nonpolyposis colorectal cancer into a genetic m odel that generates probabilities of family clustering of colo-rectal cance r. Using this model, which assumes that all familial risk for colorectal ca ncer is due to hereditary nonpolyposis colorectal cancer, the expected rela tive risks for colorectal cancer (and adenomas) associated with given types of family histories were calculated. The relative risks predicted by the m odel fairly closely matched the results found in the literature, especially those reported from a large cohort study. As observed in several studies, the model predicts that relative risks decrease sharply with age. In contra st to the elevated risk for colorectal cancer, the model predicts no elevat ed risk for adenomas associated with family history of colorectal cancer.