Journal
CANCER MEDICINE
Volume 7, Issue 5, Pages 1978-1987Publisher
WILEY
DOI: 10.1002/cam4.1445
Keywords
Cross-disease analysis; endometrial cancer; endometriosis; genome-wide association study; genetic correlation
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia [241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498]
- Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC)
- Cerylid Biosciences (Melbourne)
- Wellcome Trust [WT084766/Z/08/Z, 076113, 085475, 068545/Z/02]
- NHMRC [339435, 552402, 1031333]
- Cancer Council Queensland [4196615]
- Cancer Council Tasmania [403031, 457636]
- Cancer Research UK [C490/A10124, C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C1287/A12014]
- UK Medical Research Council [G0000934]
- European Union's Framework Programme 7 CHIBCHA grant
- Wellcome Trust Centre for Human Genetics Core Grant [090532/Z/09Z]
- European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]
- US National Institutes of Health [R01 CA128978, U19 CA148537, U19 CA148065, U19 CA148112]
- US Department of Defense [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR)
- Susan G. Komen Foundation
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- ELAN fund of the University of Erlangen
- Rudolf Bartling Foundation
- Verelst Foundation for Endometrial Cancer
- National Cancer Institute of the US Public Health Service [R01 CA122443, P30 CA15083, P50 CA136393]
- Fred C. and Katherine B. Andersen Foundation
- Mayo Foundation
- Helse Vest Grant
- University of Bergen
- Melzer Foundation
- Norwegian Cancer Society (Harald Andersens legat)
- Research Council of Norway
- Haukeland University Hospital
- Stockholm County Council [20110222, 20110483, 20110141, DF 07015]
- Karolinska Institutet [20110222, 20110483, 20110141, DF 07015]
- Swedish Labor Market Insurance [100069]
- Swedish Cancer Society [11 0439]
- Agency for Science, Technology and Research of Singapore (A*STAR)
- US National Institutes of Health
- Susan G. Komen Breast Cancer Foundation
- Ovarian Cancer Research Fund [PPD/RPCI.07]
- UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge
- National Cancer Institute (USA) [UM1 CA164920]
- National Health and Medical Research Council of Australia
- New South Wales Cancer Council
- Victorian Health Promotion Foundation (Australia)
- Victorian Breast Cancer Research Consortium
- U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia
- Cancer Council Tasmania
- National Health and Medical Research Council of Australia (NHMRC) [ID400413, ID400281]
- Ovarian Cancer Australia
- Peter MacCallum Foundation
- NHMRC
- Wellcome Senior Fellowship in Basic Biomedical Science
- Australian Research Council
- Sheffield Experimental Cancer Medicine Centre
- Breast Cancer Now
- NATIONAL CANCER INSTITUTE [U19CA148065, UM1CA164920, U19CA148112, R01CA128978, R01CA122443, P30CA015083, P50CA136393, U19CA148537] Funding Source: NIH RePORTER
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Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r(g) = 0.23, P = 9.3 x 10(-3) ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 x 10(-3)) and concordance in effect direction (P = 2.0 x 10(-3)) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P <= 10(-5) with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 x 10(-8), OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
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