The 2695 cases and 2777 controls from the E2C2 consortium were genotyped using the Illumina Human OmniExpress array (2271 cases, 2219 controls from the United States) or the Illumina Human 660W array (424 cases, 558 controls from Poland)
33 (link) and both sets were separately imputed to the 1000 Genomes Project v3 reference panel using “minimac2” software, following standard quality control steps
38 (link),39 (link).
The 288 cases from six population-based case–control studies within the Women’s Health Initiative were genotyped using five different arrays (Supplementary Data
1) and were each separately imputed using the combined 1000 Genome Project v3 and UK10K reference panels using “minimac2” software
39 (link), following standard quality measures and the exclusion of SNPs with a MAF <1%. Five controls for each case were selected randomly, matched on study.
Data were also included from the first phase of UK Biobank genotyping, comprising 636 Cancer Registry-confirmed endometrial cancer cases (as of October 2016) and 62,853 cancer-free female controls. Samples were genotyped using Affymetrix UK BiLEVE Axiom array and Affymetrix UK Biobank Axiom
® array and imputed to the combined 1000 Genome Project v3 and UK10K reference panels using SHAPEIT3
40 (link) and IMPUTE3
41 .
No analyses to identify duplicates or relatives between samples from the E2C2, WHI, or UK Biobank studies, and any other study were carried out. However, given the sampling frame of these studies, it is very unlikely that there would have been any meaningful sample overlap.
After QC exclusions, the analysis included 12,906 endometrial cancer cases (3613 of which have not been included in any previous publication) and 108,979 controls. Analyses were also carried out specifically for endometrial cancer of endometrioid histology (8758 cases) and endometrial cancer with non-endometrioid histology (1230 cases). Exploratory analyses for specific non-endometrioid histologies (serous carcinoma, carcinosarcoma, clear cell carcinoma, and mucinous carcinoma) included a small number of cases of mixed histotype, where the major component was non-endometrioid. The UK Biobank data did not include information about histology.
All participating studies were approved by research ethics committees from QIMR Berghofer Medical Research Institute, University-Clinic Erlangen, Karolinska Institutet, UZ Leuven, The Mayo Clinic, The Hunter New England Health District, The Regional Committees for Medical and Health Research Ethics Norway, and the UK National Research Ethics Service (04/Q0803/148 and 05/MRE05/1). All participants provided written, informed consent.
O’Mara T.A., Glubb D.M., Amant F., Annibali D., Ashton K., Attia J., Auer P.L., Beckmann M.W., Black A., Bolla M.K., Brauch H., Brenner H., Brinton L., Buchanan D.D., Burwinkel B., Chang-Claude J., Chanock S.J., Chen C., Chen M.M., Cheng T.H., Clarke C.L., Clendenning M., Cook L.S., Couch F.J., Cox A., Crous-Bous M., Czene K., Day F., Dennis J., Depreeuw J., Doherty J.A., Dörk T., Dowdy S.C., Dürst M., Ekici A.B., Fasching P.A., Fridley B.L., Friedenreich C.M., Fritschi L., Fung J., García-Closas M., Gaudet M.M., Giles G.G., Goode E.L., Gorman M., Haiman C.A., Hall P., Hankison S.E., Healey C.S., Hein A., Hillemanns P., Hodgson S., Hoivik E.A., Holliday E.G., Hopper J.L., Hunter D.J., Jones A., Krakstad C., Kristensen V.N., Lambrechts D., Marchand L.L., Liang X., Lindblom A., Lissowska J., Long J., Lu L., Magliocco A.M., Martin L., McEvoy M., Meindl A., Michailidou K., Milne R.L., Mints M., Montgomery G.W., Nassir R., Olsson H., Orlow I., Otton G., Palles C., Perry J.R., Peto J., Pooler L., Prescott J., Proietto T., Rebbeck T.R., Risch H.A., Rogers P.A., Rübner M., Runnebaum I., Sacerdote C., Sarto G.E., Schumacher F., Scott R.J., Setiawan V.W., Shah M., Sheng X., Shu X.O., Southey M.C., Swerdlow A.J., Tham E., Trovik J., Turman C., Tyrer J.P., Vachon C., VanDen Berg D., Vanderstichele A., Wang Z., Webb P.M., Wentzensen N., Werner H.M., Winham S.J., Wolk A., Xia L., Xiang Y.B., Yang H.P., Yu H., Zheng W., Pharoah P.D., Dunning A.M., Kraft P., De Vivo I., Tomlinson I., Easton D.F., Spurdle A.B, & Thompson D.J. (2018). Identification of nine new susceptibility loci for endometrial cancer. Nature Communications, 9, 3166.