title: Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium.
abstract: 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.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Veronica Wendy
authors.initials: VW
authors.lastname: Setiawan
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Doherty
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.forename: Angela
authors.initials: A
authors.lastname: Demichele
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Marc T
authors.initials: MT
authors.lastname: Goodman
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Horn-Ross
authors.forename: James V
authors.initials: JV
authors.lastname: Lacey
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Galina
authors.initials: G
authors.lastname: Lurie
authors.forename: Monica
authors.initials: M
authors.lastname: McGrath
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
mesh_terms: 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
chemical_list: D004967:Estrogens; D001141:Aromatase