Increased Incidence of Colorectal Cancer in Patients with Prior Endometrial Cancer: A Populationbased U.S. Study: ACG Colorectal Cancer Prevention Award

Abstract

Purpose: Recent population-based study from Manitoba, Canada showed that endometrial cancer (EC) survivors were at increased risk of colorectal cancer (CRC). The evidence thus far had been equivocal and limited to regional registries. We evaluated the risk of subsequent CRC in endometrial cancer patients using Surveillance, Epidemiology, and End Results (SEER-9) registry of U.S. population. Methods: The National Cancer Institute's SEER-9 database was queried to identify adult patients between 1973-2000 with an index diagnosis of EC (ICD-O-3 code C54.1), after excluding any patient with cancer prior to being listed with SEER and allowing sufficient time for subsequent CRC to develop. Relative risk of developing CRC was determined comparing the observed incidence of subsequent CRC amongst EC survivors to that in general population with similar demographics and time period. Byar's accurate approximation to the exact Poisson distribution was used to calculate 95% confidence intervals (CI) and to determine statistical significance. All analysis was performed using SEER*STAT software. Results: Patients with history of EC had 1.35 fold greater incidence of CRC than controls (RR 1.35, 95% CI: 1.25-1.47) with an absolute risk excess of 6.14 cases per 1,000 as observed over 253,101 person years of follow-up. The mean age of developing EC and for subsequent CRC were 63.96 and 73.62, respectively. This increase in risk was greatest in the population diagnosed with EC between 18-49 years (RR 4.81, 95% CI: 2.80-7.70, risk excess 6.69 cases per 1,000) with the shortest latency period between EC and CRC (mean age EC: 43.17 and mean age CRC: 45.17). The EC survivors who had received radiation had a marginal increase in risk (RR 1.50; 95% CI: 1.30-1.73) when compared to those who had not been treated with radiation (RR 1.28; 95% CI: 1.15-1.41). The RR for subsequent CRC was only found to be significant in period after 1990 (RR-1.35; 95% CI: 1.24-1.46), but not in the preceding period 1973-1990 (RR-1.53; 95% CI: 0.95-2.34), which could likely be due to inadequate screening for CRC. The reciprocal analysis of uterine corpus-EC risk amongst index primary CRC also showed a similar increase (RR 1.17; 95% CI: 1.25-1.40) with peak age of EC noted in younger (20-50) CRC patients (RR 6.42; 95% CI: 4.98-8.79). Conclusion: Our results showed increased risk of CRC amongst EC survivors with an appreciable risk in those developing EC at young age (<50). These results support early CRC screening in younger EC patients (<50). Several factors contributing to this observed bidirectional association including genetics, radiation exposure, and more aggressive screening among cancer survivors would warrant further investigation.