GENETIC-IMPLICATIONS OF DOUBLE PRIMARY CANCERS OF THE COLORECTUM AND ENDOMETRIUM

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dom inant condition predisposing to cancers of the colorectum and endometr ium. Endometrial cancer is the most commonly occurring extracolonic ca ncer in HNPCC. Estimates of the cumulative incidence of endometrial ca ncer in women with mutations in the HNPCC genes range from 22-43%. In order to determine how frequently double primary cancers of the colore ctum and endometrium are the result of a hereditary factor, we conduct ed a registry based study in Ontario and Quebec, Canada. We obtained p edigrees on 80 women diagnosed with double primary cancers of the colo rectum and endometrium at less than 70 years of age. Family histories of cancer were obtained for all first degree relatives of these women and cancer rates were compared with age standardised provincial incide nce rates in order to estimate the relative risks. There was a total o f 82 cancers observed in relatives below the age of 55, compared with 31.2 expected, giving a relative risk of 2.6 (95% confidence interval (CI) 2.1-3.3). The relative risk for colorectal cancer below 55 was 16 .1 (95% CI 11.6-21.8). This risk decreased with increasing age of onse t of cancers in probands. For probands with both colorectal and endome trial cancer diagnosed under the age of 55, the relative risk of color ectal cancer in relatives below the age of 55 was 30.5 (95% CI 18.8-46 .6). Similar patterns were observed for endometrial and pancreatic can cer. There were non-significant increases in rates of cancer of the oe sophagus, stomach, small intestine, and bladder. There was no increase d risk of breast cancer. The risk of lung cancer was decreased, especi ally in older relatives. Our findings indicate the presence of a signi ficant genetic component of cancer in women with double primary cancer s of the colorectum and endometrium.