Identification of nine new susceptibility loci for endometrial cancer.

Authors:
Ms Maggie Gorman, RN
Ms Maggie Gorman, RN
Institute of Cancer Research
London | United Kingdom
Dr Dylan Glubb, PhD
Dr Dylan Glubb, PhD
QIMR Berghofer Medical Research Institute
Brisbane, QLD | Australia
Tracy A O'Mara Dylan M Glubb Frederic Amant Daniela Annibali Katie Ashton John Attia Paul L Auer Matthias W Beckmann Amanda Black Manjeet K Bolla Hiltrud Brauch Hermann Brenner Louise Brinton Daniel D Buchanan Barbara Burwinkel Jenny Chang-Claude Stephen J Chanock Chu Chen Maxine M Chen Timothy H T Cheng Christine L Clarke Mark Clendenning Linda S Cook Fergus J Couch Angela Cox Marta Crous-Bous Kamila Czene Felix Day Joe Dennis Jeroen Depreeuw Jennifer Anne Doherty Thilo Dörk Sean C Dowdy Matthias Dürst Arif B Ekici Peter A Fasching Brooke L Fridley Christine M Friedenreich Lin Fritschi Jenny Fung Montserrat García-Closas Mia M Gaudet Graham G Giles Ellen L Goode Christopher A Haiman Per Hall Susan E Hankison Catherine S Healey Alexander Hein Peter Hillemanns Shirley Hodgson Erling A Hoivik Elizabeth G Holliday John L Hopper David J Hunter Angela Jones Camilla Krakstad Vessela N Kristensen Diether Lambrechts Loic Le Marchand Xiaolin Liang Annika Lindblom Jolanta Lissowska Jirong Long Lingeng Lu Anthony M Magliocco Lynn Martin Mark McEvoy Alfons Meindl Kyriaki Michailidou Roger L Milne Miriam Mints Grant W Montgomery Rami Nassir Håkan Olsson Irene Orlow Geoffrey Otton Claire Palles John R B Perry Julian Peto Loreall Pooler Jennifer Prescott Tony Proietto Timothy R Rebbeck Harvey A Risch Peter A W Rogers Matthias Rübner Ingo Runnebaum Carlotta Sacerdote Gloria E Sarto Fredrick Schumacher Rodney J Scott V Wendy Setiawan Mitul Shah Xin Sheng Xiao-Ou Shu Melissa C Southey Anthony J Swerdlow Emma Tham Jone Trovik Constance Turman Jonathan P Tyrer Celine Vachon David VanDen Berg Adriaan Vanderstichele Zhaoming Wang Penelope M Webb Nicolas Wentzensen Henrica M J Werner Stacey J Winham Alicja Wolk Lucy Xia Yong-Bing Xiang Hannah P Yang Herbert Yu Wei Zheng Paul D P Pharoah Alison M Dunning Peter Kraft Immaculata De Vivo Ian Tomlinson Douglas F Easton Amanda B Spurdle Deborah J Thompson

Nat Commun 2018 08 9;9(1):3166. Epub 2018 Aug 9.

Department of Public Health and Primary Care, University of Cambridge, Centre for Cancer Genetic Epidemiology, Cambridge, CB1 8RN, UK.

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

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http://dx.doi.org/10.1038/s41467-018-05427-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085317PMC
August 2018
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