No association between FTO or HHEX and endometrial cancer risk.
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.
Gaudet
Mia M
MM
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
Yang
Hannah P
HP
Bosquet
Jesus Gonzalez
JG
Healey
Catherine S
CS
Ahmed
Shahana
S
Dunning
Alison M
AM
Easton
Doug F
DF
Spurdle
Amanda B
AB
Ferguson
Kaltin
K
O'Mara
Tracy
T
Lambrechts
Diether
D
Despierre
Evelyn
E
Vergote
Ignace
I
Amant
Frederic
F
Lacey
James V
JV
Lissowska
Jola
J
Peplonska
Beata
B
Brinton
Louise A
LA
Chanock
Stephen
S
Garcia-Closas
Montserrat
M
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
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