Benign extracolonic manifestations associated with hereditary nonpolyposis colorectal cancer

Hereditary nonpolypotic colorectal cancer (HNPCC) patients have a high predisposition to develop colorectal and associated cancers. The mismatch repair genes (MMR) have been demonstrated to be altered in the germline of patients with HNPCC. The question arises whether defective MMR targets candidate genes other than genes involved in cancerogenesis. In this retrospective study, we analyzed the frequency of 23 extracolonic manifestations encountered in familial colorectal cancer patients. In a matched case-control design, two sets of pairs were identified with sporadic colorectal cancer and esophageal cancer. Coronary heart disease (CHD) and degenerative joint disease (DJD) were significantly increased in cases versus controls with esophageal cancer. This tendency was notable but not significant in the patients with sporadic colon cancer. In the combined analysis with both sets of controls, the observed difference was significant. This observation indicates that defective MMR may not only affect pathways leading to neoplasia. Prospective clinical studies should focus on exact patient histories in order to detect associated nonmalignant disease.