Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.
Common variants in CYP19A1 (the A alleles of rs749292 and rs727479) have been associated with a 10% to 20% increase in circulating estrogen levels in postmenopausal women. We hypothesized that the presence of one or both A alleles in these single nucleotide polymorphisms (SNP) is associated with increased endometrial cancer risk. We tested this hypothesis in a large pooled analysis of 4,998 endometrial cancer cases and 8,285 controls from 10 studies in the Epidemiology of Endometrial Cancer Consortium. The majority of women (>66%) were whites, with smaller proportions of other races and ethnic groups (blacks, Asians, and Latinas) also included in this pooled analysis. Unconditional logistic regression was used to model the association between SNPs/haplotypes and endometrial cancer risk. Carrying the A allele of either of these SNPs was associated with an increased risk of endometrial cancer, with pooled odds ratios per allele of 1.14, 95% confidence interval of 1.09-1.21, and P = 7.1 x 10(-7) for rs749292, and odds ratio per allele of 1.08, 95% confidence interval of 1.02-1.14, and P = 0.009 for rs727479. For rs749292, these associations were generally stronger among women age >or=55 years. For both SNPs, risk increased with increasing body mass index, and for rs727479, this pattern seemed stronger among women age >or=55 years (P interaction = 0.007). The combination of A alleles in the two SNPs, either by direct count or by haplotype analysis, did not increase risk above that observed for the individual SNPs. Our study provides evidence that CYP19A1 genetic variation influences susceptibility to endometrial cancer, particularly among older and obese women.
Setiawan
Veronica Wendy
VW
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Doherty
Jennifer A
JA
Shu
Xiao-Ou
XO
Akbari
Mohammad R
MR
Chen
Chu
C
De Vivo
Immaculata
I
Demichele
Angela
A
Garcia-Closas
Montserrat
M
Goodman
Marc T
MT
Haiman
Christopher A
CA
Hankinson
Susan E
SE
Henderson
Brian E
BE
Horn-Ross
Pamela L
PL
Lacey
James V
JV
Le Marchand
Loic
L
Levine
Douglas A
DA
Liang
Xiaolin
X
Lissowska
Jolanta
J
Lurie
Galina
G
McGrath
Monica
M
Narod
Steven A
SA
Rebbeck
Timothy R
TR
Ursin
Giske
G
Weiss
Noel S
NS
Xiang
Yong-Bing
YB
Yang
Hannah P
HP
Zheng
Wei
W
Olson
Sara H
SH
D000367:Age Factors; D000368:Aged; D000483:Alleles; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D004967:Estrogens; D001141:Aromatase