The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by increased risk for cancer, especially colorectal cancer. It has been recommended that colon cancer control programs for family members be expanded to include endometrial cancer, the commonest extracolonic cancer observed in HNPCC families. We estimated the age-specific and cumulative endometrial cancer risk for women at high risk for HNPCC.

Family history data from three large HNPCC registries were combined for this study. High risk family members were identified without regard to extracolonic cancer. Life table methods were used to calculate estimates of risk.

One thousand eighteen women from 86 families were included in the study. Cumulative incidence was 20% by age 70, compared to 3% in the general population. Risk was highest in women most likely to carry the HNPCC gene (P < 0.001). In this group, during the highest risk years (age 40 to 60), average annual risk exceeded 1%. There was no significant difference among the registries, despite different ascertainment practices regarding endometrial cancer.

Interventions to reduce endometrial cancer morbidity and mortality are justified by the risk levels observed. Prophylactic total hysterectomy and bilateral salpingo-oophorectomy should be recommended to women in HNPCC families who have a syndrome cancer or offspring with a syndrome cancer. Endometrial cancer screening should be available to women at high risk. Studies of screening protocols are needed.