CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Thompson DJ, O'Mara TA, Glubb DM, Painter JN, Cheng T, Folkerd E, Doody D, Dennis J, Webb PM, Gorman M, Martin L, Hodgson S, Michailidou K, Tyrer JP, Maranian MJ, Hall P, Czene K, Darabi H, Li J, Fasching PA, Hein A, Beckmann M, Ekici AB, Doerk T, Hillemanns P, Duerst M, Runnebaum I, Zhao H, Depreeuw J, Schrauwen S, Amant F, Goode EL, Fridley BL, Dowdy SC, Winham SJ, Salvesen HB, Trovik J, Njolstad TS, Werner HMJ, Ashton K, Proietto T, Otton G, Carvajal-Carmona L, Tham E, Liu T, Mints M, Scott RJ, Mcevoy M, Attia J, Holliday EG, Montgomery GW, Martin NG, Nyholt DR, Henders AK, Hopper JL, Traficante N, Rübner M, Swerdlow AJ, Burwinkel B, Brenner H, Meindl A, Brauch H, Lindblom A, Lambrechts D, Chang-Claude J, Couch FJ, Giles GG, Kristensen VN, Cox A, Bolla MK, Wang Q, Bojesen SE, Shah M, Luben R, Khaw KT, Pharoah PDP, Dunning AM, Tomlinson I, Dowsett M, Easton DF, Spurdle AB
Zeitschrift: Endocrine-Related Cancer
Jahr der Veröffentlichung: 2016
Band: 23
Heftnummer: 2
Seitenbereich: 77-91
ISSN: 1351-0088


Abstract


Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with 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=4.8×10(-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 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.



FAU-Autoren / FAU-Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Hein, Alexander PD Dr.
Frauenklinik
Rübner, Matthias Dr. rer. nat.
Frauenklinik


Autor(en) der externen Einrichtung(en)
Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC))
Deutsches Krebsforschungszentrum (DKFZ)
Friedrich-Schiller-Universität Jena
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
John Hunter Hospital
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Mayo Clinic
Oslo University Hospital / Oslo Universitetssykehus
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Ruprecht-Karls-Universität Heidelberg
St George's, University of London (SGUL) / St George's Hospital Medical School
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The Royal Marsden NHS Foundation Trust
The University of Melbourne
Universidad del Tolima
University of Bergen
University of California Los Angeles (UCLA)
University of Cambridge
University of Copenhagen
University of Kansas (KU)
University of Newcastle (UoN)
University of Oxford
University of Sheffield


Zitierweisen

APA:
Thompson, D.J., O'Mara, T.A., Glubb, D.M., Painter, J.N., Cheng, T., Folkerd, E.,... Spurdle, A.B. (2016). CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer. Endocrine-Related Cancer, 23(2), 77-91. https://dx.doi.org/10.1530/ERC-15-0386

MLA:
Thompson, Deborah J., et al. "CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer." Endocrine-Related Cancer 23.2 (2016): 77-91.

BibTeX: 

Zuletzt aktualisiert 2018-06-10 um 03:07