title: Association of specific PTEN/10q haplotypes with endometrial cancer phenotypes in African-American and European American women.
abstract: OBJECTIVE
  Endometrial 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Eighteen 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Jazmine
authors.initials: J
authors.lastname: Sutton
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Orloff
authors.affiliation: Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Women's Health and Obstetrics/Gynecology Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Michener
authors.affiliation: Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Chiesa-Vottero
authors.affiliation: Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Prayson
authors.affiliation: Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Nowacki
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Genetics and Genome Sciences, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44116, USA; Germline High Risk Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44116, USA. Electronic address: engc@ccf.org.
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Disparity; Endometrial cancer; Haplotypes; PTEN