Differences in endometrial cancer molecular portraits based on ethnicity in The Cancer Genome Atlas


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David Guttery1,Kevin Blighe1,Konstantinos Polymeros2,Paul Symonds1,Salvador Macip1,Esther Moss1
1University of Leicester,2Univerisyt of Leicester



It is clear that racial/ethnic differences in endometrial cancer (EC) incidence, age at presentation and survival exist; however, it is unclear whether this disparity is driven by inherent genetic alterations in the primary tumour.  


We investigated the molecular features of EC using data in the TCGA, including somatic mutations, gene expression, DNA methylation and copy-number aberrations (CNAs) and contrasted them between BoAA, Caucasian and Asian women.


There were 503 patients with EC, including 374 Caucasian (mean [SD] age at diagnosis 64.5 [10.8] years) 109 Black or African American (BoAA) (mean [SD] age at diagnosis 64.9 [10.1] years), and 20 Asian patients (mean [SD] age at diagnosis 54.2 [12.2] years). Asian women were more likely to be diagnosed at younger age (odds ratio (OR), 3.432; 95% CI, 1.338-8.6; P = 0.011), whereas BoAAs were more likely to have serous type tumors (OR, 2.061; 95% CI 1.252-3.356; P = 0.008) and higher BMI (OR, 2.937; 95% CI, 1.420-6.887; P = 0.0008). No difference in overall or disease-free survival was evident. Mutation and somatic copy number alteration (SCNA) analysis revealed an enrichment of TP53 mutations in BoAAs; whereas POLE and RPL22 mutations were more frequent in Caucasians. We also found Asian women to harbour more than double the number of mutations per tumour. Major recurrent SCNA racial differences were observed at chr1q, chr8, chr10, and chr16, which distinguished BoAA tumours into 4 groups and Caucasian tumours into 5. Finally, we observed a significantly higher frequency of mutations in DNA mismatch repair genes associated with Lynch syndrome in Asians.


We have highlighted clinically-relevant molecular differences that intrinsically characterise racial disparities between Caucasian, Asian and BoAA ECs. These data can potentially form the basis for molecular targeted therapies, and also explain why Asians are frequently diagnosed at an earlier age, potentiating screening studies in future.