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

Abstract

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.