@article{922eed2c9d7140c781387c505b789f08,
title = "CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer",
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.",
keywords = "CYP19A1, Endometrial cancer, Estradiol",
author = "{Australian National Endometrial Cancer Study Group (ANECS)} and Thompson, {Deborah J.} and O'Mara, {Tracy A.} and Glubb, {Dylan M.} and Painter, {Jodie N.} and Timothy Cheng and Elizabeth Folkerd and Deborah Doody and Joe Dennis and Webb, {Penelope M.} and Maggie Gorman and Lynn Martin and Shirley Hodgson and Kyriaki Michailidou and Tyrer, {Jonathan P.} and Maranian, {Mel J.} and Per Hall and Kamila Czene and Hatef Darabi and Jingmei Li and Fasching, {Peter A.} and Alexander Hein and Beckmann, {Matthias W.} and Ekici, {Arif B.} and Thilo D{\"o}rk and Peter Hillemanns and Matthias D{\"u}rst and Ingo Runnebaum and Hui Zhao and Jeroen Depreeuw and Stefanie Schrauwen and Frederic Amant and Goode, {Ellen L.} and Fridley, {Brooke L.} and Dowdy, {Sean C.} and Winham, {Stacey J.} and Salvesen, {Helga B.} and Jone Trovik and Tormund, {Njolstad S.} and Werner, {Henrica M.J.} and Katie Ashton and Tony Proietto and Geoffrey Otton and Luis Carvajal-Carmona and Emma Tham and Tao Liu and Miriam Mints and Scott, {Rodney J.} and Mark McEvoy and John Attia and Couch, {Fergus J.}",
note = "Funding Information: The authors thank many individuals who participated in this study and numerous institutions and their staff who supported recruitment, detailed in full in the Supplementary Text, which is linked to the online version of the paper at http://dx.doi.org/10.1530/ERC-15-0386. Publisher Copyright: {\textcopyright} 2016 The authors.",
year = "2016",
month = feb,
doi = "10.1530/ERC-15-0386",
language = "English (US)",
volume = "23",
pages = "77--91",
journal = "Endocrine-Related Cancer",
issn = "1351-0088",
publisher = "Society for Endocrinology",
number = "2",
}