title: Genetic variation in the progesterone receptor gene and risk of endometrial cancer: a haplotype-based approach.
abstract: BACKGROUND
  It is well established that estrogen increases endometrial cancer risk, whereas progesterone opposes the estrogen effects. The PROGINS allele of the progesterone receptor (PGR) gene reduces the function of PGR and has been associated with increased risk of the endometrioid type ovarian cancer. We investigated whether genetic variation in PGR is also associated with endometrial cancer risk using a haplotype-based approach.
  
  
  METHODS
  We pooled data from two endometrial cancer case-control studies that were nested within two prospective cohorts, the Multiethnic Cohort Study and the California Teachers Study. Seventeen haplotype-tagging single nucleotide polymorphisms (SNPs) across four linkage disequilibrium (LD) blocks spanning the PGR locus were genotyped in 583 incident cases and 1936 control women. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each haplotype were estimated using conditional logistic regression, stratified by age and ethnicity.
  
  
  RESULTS
  Genetic variation in LD block 3 of the PGR locus was associated with endometrial cancer risk (P(global test) = 0.002), with haplotypes 3C, 3D and 3F associated with 31-34% increased risk. Among whites (383 cases/840 controls), genetic variation in all four blocks was associated with increased endometrial cancer risk (P(global test) = 0.010, 0.013, 0.005 and 0.020). Haplotypes containing the PROGINS allele and several haplotypes in blocks 1, 3 and 4 were associated with 34-77% increased risk among whites. SNP analyses for whites suggested that rs608995, partially linked to the PROGINS allele (r(2) = 0.6), was associated with increased risk (OR = 1.30, 95% CI = 1.06-1.59).
  
  
  CONCLUSIONS
  Our results suggest that genetic variation in the PGR region is associated with endometrial cancer risk.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Chris
authors.initials: C
authors.lastname: Hsu
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Pedram
authors.initials: P
authors.lastname: Razavi
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Horn-Ross
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: V Wendy
authors.initials: VW
authors.lastname: Setiawan
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006254:Hawaii; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D011980:Receptors, Progesterone