Genetics in the development of endometrial cancer: How does it affect East Asians?

Abstract

e13022 Background: Obesity and Lynch syndrome are well-known risk factors for the development of endometrial cancer. However, there is a paucity of data comparing patients across multiple ethnicities. Methods: All patients diagnosed with endometrial cancer or complex atypical hyperplasia between 2012 and 2015 were retrospectively identified and evaluated. Comparative statistical analyses were performed and stratified by ethnicity with appropriate two-sided statistical tests. Results: A total of 506 patients were diagnosed with endometrial cancer (n = 447) or complex atypical hyperplasia (n = 59) and of these, 31 were East Asian (EA, 6.3%). The remaining 475 patients (93.9%) were of Caucasian, black, Latino, South Asian, Southeast Asian or other unspecified ethnicity. Compared to other patients, EA were diagnosed at a younger age (median age 53 vs 62, p = 0.0003) and had lower body mass indices (BMI) (median BMI 23.0 vs 30.7, p < 0.0001). There were no differences in stage, tumor grade or histology. Differences in age and BMI remained significant despite controlling for these factors on multivariate analysis. Of the EA group, 10 of 31 patients (32.3%) underwent genetic testing and of these, three (30.0%) were found to have a germline mutation in a mismatch repair (MMR) gene. All three patients were of Chinese ancestry, and two had mutations in MLH1 and one in MSH2. In comparison, 69 (14.5%) of the remaining 475 had genetic testing, and six (8.7%) were diagnosed with Lynch syndrome. Chinese patients were more likely to have Lynch syndrome (42.9% vs 8.7%, p= 0.04). There were no differences found in family history of Lynch-related cancers between Chinese and other patients. There was no correlation between germline mutations and MMR testing on tumor immunohistochemistry. All three Chinese patients with Lynch syndrome had negative MMR tumor testing. Conclusions: EA patients with endometrial cancer are diagnosed at younger ages and with lower BMIs compared to patients of other ethnic backgrounds. Chinese patients have a high rate of germline Lynch mutations despite negative tumor MMR testing. EA, particularly Chinese patients, may represent a high-risk cohort, and referral for genetic counseling regardless of tumor MMR testing should be considered.