Risk of cancer revealed by follow-up of families with hereditary non-polyposis colorectal cancer: a population-based study

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by susceptibility to large-bowel cancer, frequently with early onset and localized in the right colon. Several tumours of other sites may also occur with increased frequency in these families. During the period 1984-1989, 28 families with HNPCC were identified in our Health Care District through a population-based colorectal cancer registry. Moreover, 61 additional families were selected and classified as having ´´suspected´´ HNPCC. The objective of the present study is to report the occurrence of new cases of cancer in the 5- to 6-year follow-up of individuals at risk of tumour development in either HNPCC or ´´suspected´´ families. There were 374 family members at risk in HNPCC and 468 in ´´suspected´´ families, contributing, respectively, 2,377 and 2,712 persons/year at risk. Thirty-four new tumours developed among HNPCC family members vs. 29.3 expected; however, the occurrence of colorectal cancer in this group was significantly higher than expected, and this excess was particularly evident in the age-groups 41-50 and 51-60. In ´´suspected´´ HNPCC, 38 new tumours developed vs. 24.5 expected; at variance with the other group, besides colorectal neoplasms, lung, liver and brain tumours also occurred significantly in excess. Moreover, the increased risk was uniformly distributed among different age-groups. In conclusion, HNPCC family members are at increased risk of developing colorectal cancer, with an earlier onset than the general population; in contrast, high-risk individuals in ´´suspected´´ HNPCC families seem to be prone to a broader neoplastic spectrum, and risk of tumours does not seem to be limited to any particular age-group.