Abstracts
1997 Digestive Disease Week

Cumulative incidence of extracolonic and colorectal cancers in MLH1 and MSH2 mutation carriers of HNPCC.

KM Lin, M Shashidharan, CA Ternent, AG Thorson, GJ Blatchford, MA Christensen, S Lemon, HT Lynch. Department of Colorectal Surgery and Preventive Medicine, Creighton University School of Medicine, Omaha, NE.

The extracolonic tumor spectrum of hereditary nonpolyposis colorectal cancer (HNPCC) includes endometrium, ovary, stomach, small bowel, breast, hepatobiliary and urologic system. Purpose: The cumulative incidence of extracolonic and colorectal cancers was determined for MLH1 and MSH2 mutation carriers in hereditary nonpolyposis colorectal cancer. Methods: Twenty-two females and 27 males from 2 HNPCC kindreds underwent genetic testing which revealed a MSH2 germline mutation. Likewise, 28 females and 28 males from 2 HNPCC kindreds were found to have a MLH1 germline mutation. The cumulative incidence of extracolonic and colorectal cancers by age 60 was calculated for each group and compared. Results: The cumulative incidence of extracolonic cancers was 69% in MSH2 females compared to 34% in MSH2 males (p=0.042). This difference was not identified between MLH1 females and males. When analyzing each gender separately, the extracolonic cancer cumulative incidence was 69% in MSH2 females compared to 19% in MLH1 females (p=0.024) and 34% in MSH2 males compared to 5% in MLH1 males (p= 0.046). The cumulative colorectal cancer incidence was 90% in MSH2 and 91% in MLH1 members. Conclusion: By age 60, the cumulative incidence of extracolonic cancers was higher in females than males with the MSH2 germline mutation. Carriers of the MSH2 germline mutation had a higher cumulative incidence of extracolonic cancers than the MLH1 carriers. Colorectal cancer cumulative incidence was equal in the two germline mutations. [Figure not available.]