ObjectiveEndometrial carcinoma (EC), the most common gynecologic malignancy in the United States, affects European American (EA) women more frequently than African-American (AA) women. Yet, AA women are more likely to die from EC. Proposed etiologies for this racial disparity, such as socioeconomic status, aggressive, non-endometrioid tumor histology, and comorbid conditions, do not account for the entire disparity experienced by AA women, suggesting an unexplored genetic component. Germline mutations in PTEN cause Cowden syndrome (CS), which increases lifetime risk of endometrial cancer. In addition, somatic PTEN silencing is one of the most common initiating events in sporadic EC. Therefore, we hypothesized that specific PTEN haplotypes in the AA population may directly predispose AA women to unfavorable tumor characteristics when diagnosed with EC. MethodsWe conducted a case–control association study of germline variations in and around the PTEN/10q region between 53 EA and 51 AA EC cases and ethnic controls. ResultsEighteen tag SNPs with minor allele frequency ≥0.1, were genotyped and used to reconstruct haplotypes. Forty-eight ancestry informative markers were genotyped control for population stratification. Two haplotypes were overrepresented in AA, and there was a trend towards tumors with higher stage and grade in patients with these haplotypes. One haplotype was overrepresented in the EA population with a trend towards more endometrioid tumors. ConclusionsWe show that specific PTEN/10q haplotypes are significantly different between EA and AA individuals (p≤0.02), and specific haplotypes may increase the risk of unfavorable tumor phenotypes in AA women diagnosed with EC.