title: No association between FTO or HHEX and endometrial cancer risk.
abstract: BACKGROUND
  Obesity and diabetes are known risk factors for endometrial cancer; thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies.
  
  
  METHODS
  We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP each in FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs (as an ordinal variable) and endometrial cancer risk using unconditional logistic regression models, controlling for age and site.
  
  
  RESULTS
  In the primary study, the most significant finding in FTO was rs12927155 (OR, 1.56; 95% CI, 1.21-2.01; P = 5.8 x 10(-4)), and in HHEX, it was rs1111875 (OR, 0.80; 95% CI, 0.66-0.97; P = 0.026). In the validation studies, the pooled per allele OR, adjusted for age and study for FTO, was rs12927155 (OR, 0.94; 95% CI, 0.83-1.06; P = 0.29), whereas for HHEX, it was rs1111875 (OR, 1.00; 95% CI, 0.92-1.10; P = 0.96).
  
  
  CONCLUSIONS
  Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans were not associated with endometrial cancer risk.
  
  
  CONCLUSIONS
  Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects.
authors.affiliation: Department of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461, USA. mia.gaudet@einstein.yu.edu
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.forename: Jesus Gonzalez
authors.initials: JG
authors.lastname: Bosquet
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Healey
authors.forename: Shahana
authors.initials: S
authors.lastname: Ahmed
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Doug F
authors.initials: DF
authors.lastname: Easton
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: Kaltin
authors.initials: K
authors.lastname: Ferguson
authors.forename: Tracy
authors.initials: T
authors.lastname: O'Mara
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Evelyn
authors.initials: E
authors.lastname: Despierre
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
authors.forename: Jola
authors.initials: J
authors.lastname: Lissowska
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C078492:HHEX protein, human; D018398:Homeodomain Proteins; D011506:Proteins; D014157:Transcription Factors; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human