title: Genetic variants in ER cofactor genes and endometrial cancer risk.
abstract: Given that the transcriptional regulatory activity of estrogen receptor (ER) is modulated by its biochemical cofactors, genetic variation within the ER cofactor genes may alter cellular response to estrogen exposure and consequently modify the risk for endometrial cancer. We genotyped 685 tagging SNPs within 60 ER cofactor genes in 564 endometrial cancer cases and 1,510 controls from Sweden, and tested their associations with the risk of endometrial cancer. We investigated the associations of individual SNPs by using a trend test as well as multiple SNPs within a gene or gene complex by using multi-variant association analysis. No significant association was observed for any individual SNPs or genes, but a marginal association of the cumulative genetic variation of the NCOA2 complex as a whole (NCOA2, CARM1, CREBBP, PRMT1 and EP300) with endometrial cancer risk was observed (P(adjusted) = 0.033). However, the association failed to be replicated in an independent European dataset of 1265 cases and 5190 controls (P = 0.71). The results indicate that common genetic variants within ER cofactor genes are unlikely to play a significant role in endometrial cancer risk in European population.
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Low
authors.forename: Jia Nee
authors.initials: JN
authors.lastname: Foo
authors.forename: Hatef
authors.initials: H
authors.lastname: Darabi
authors.forename: Kristjana
authors.initials: K
authors.lastname: Einarsdόttir
authors.forename: Keith
authors.initials: K
authors.lastname: Humphreys
authors.forename: Amanda
authors.initials: A
authors.lastname: Spurdle
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Thompson
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Kamila
authors.initials: K
authors.lastname: Czene
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000368:Aged; D050882:CREB-Binding Protein / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000378:metabolism; D015203:Reproducibility of Results; D012306:Risk; D013548:Sweden; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D050882:CREB-Binding Protein; D000075702:Nedd4 Ubiquitin Protein Ligases; D044767:Ubiquitin-Protein Ligases