- Title
- CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer
- Creator
- Thompson, Deborah J.; O'Mara, Tracy A.; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P.; Maranian, Mel J.; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A.; Glubb, Dylan M.; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G.; Painter, Jodie N.; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M.; Gorman, Maggie
- Relation
- Endocrine - Related Cancer Vol. 23, Issue 2, p. 77-91
- Publisher Link
- http://dx.doi.org/10.1530/ERC-15-0386
- Publisher
- BioScientifica
- Resource Type
- journal article
- Date
- 2016
- Description
- Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E₂) concentrations.We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10-11). SNP rs727479 was also among those most strongly associated with circulating E₂ concentrations in 2767 post-menopausal controls (P=7.4x10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E₂ concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E₂. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.
- Subject
- endometrial cancer; CYP19A1; estradiol
- Identifier
- http://hdl.handle.net/1959.13/1320127
- Identifier
- uon:24073
- Identifier
- ISSN:1351-0088
- Language
- eng
- Full Text
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