title: FASN, dietary fat intake, and risk of uterine leiomyomata in the Black Women's Health Study.
abstract: OBJECTIVE
  To replicate results from a previous genome-wide association study of European ancestry women, in which a positive association was found between uterine leiomyomata (UL) and rs4247357, a single-nucleotide polymorphism located near the fatty acid synthase (FASN) gene.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  African-American women aged 23-50 years, who were premenopausal and had an intact uterus in 1997.
  
  
  METHODS
  None.
  
  
  METHODS
  We genotyped rs4247357 among 2,301 incident UL cases and 3,005 controls from the Black Women's Health Study (1997-2011). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression with control for age, geographic region of residence, and percent European ancestry using a panel of validated ancestry informative markers.
  
  
  RESULTS
  Overall, rs4247357 was not associated with UL risk. Relative to the CC genotype, ORs were 1.04 (95% CI 0.92-1.19) for the AC genotype and 1.09 (95% CI 0.93-1.29) for the AA genotype. A positive association was found, however, among those with higher European ancestry (≥40%). Relative to the CC genotype, ORs were 2.03 (95% CI 1.12-3.69) for the AC genotype and 2.44 (95% CI 1.20-4.96) for the AA genotype. Dietary fat intake also appeared to modify the FASN-UL association.
  
  
  CONCLUSIONS
  Although there was little overall association between rs4247357 and UL risk, a positive association was observed among women with ≥40% European ancestry. Direct sequencing of this genomic region might be warranted to determine whether rs4247357, or some other variant, is causally related to UL.
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts. Electronic address: lwise@bu.edu.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wise
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rosenberg
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Haddad
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, Massachusetts.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narváez
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004041:Dietary Fats / Q000009:adverse effects*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics*; D005247:Feeding Behavior / Q000208:ethnology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007889:Leiomyoma / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D060728:Reproductive Health / Q000208:ethnology; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics; D016387:Women's Health / Q000208:ethnology*; D055815:Young Adult
chemical_list: D004041:Dietary Fats; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: African Americans; fatty acids; genetics; prospective studies; uterine neoplasms