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https://doi.org/10.1530/ERC-15-0386
Title: | CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer | Authors: | Thompson, D.J O'Mara, T.A Glubb, D.M |
Keywords: | aromatase estradiol aromatase CYP19A1 protein, human estradiol Article cancer risk case control study controlled study endometrium cancer female gene mapping genetic association genetic variability genotype environment interaction hormone determination human information retrieval major clinical study Mendelian randomization analysis phenotype postmenopause risk assessment single nucleotide polymorphism age allele blood body mass Endometrial Neoplasms genetic association study genetic predisposition genetics genotype genotype environment interaction pathology single nucleotide polymorphism Age Factors Alleles Aromatase Body Mass Index Case-Control Studies Endometrial Neoplasms Estradiol Female Gene-Environment Interaction Genetic Association Studies Genetic Predisposition to Disease Genotype Humans Phenotype Polymorphism, Single Nucleotide |
Issue Date: | 2016 | Publisher: | BioScientifica Ltd. | Citation: | Thompson, D.J, O'Mara, T.A, Glubb, D.M (2016). CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer. Endocrine-Related Cancer 23 (2) : 77-91. ScholarBank@NUS Repository. https://doi.org/10.1530/ERC-15-0386 | Rights: | Attribution 4.0 International | Abstract: | Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancerandwith estradiol (E2) concentrations.We analyzed2937singlenucleotidepolymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome widesignificant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10-11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10-8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by theobservedeffectonE2 concentrations (1.09, CI=1.03-1.21), consistentwith 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 associationswith rs727479 were stronger amongwomen with a higher BMI (PinteractionZ0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. © 2016 The authors. | Source Title: | Endocrine-Related Cancer | URI: | https://scholarbank.nus.edu.sg/handle/10635/179602 | ISSN: | 1351-0088 | DOI: | 10.1530/ERC-15-0386 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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