Kate Lawrenson1, Fengju Song2, Dennis J Hazelett3, Siddhartha P Kar4, Jonathan Tyrer4, Catherine M Phelan5, Rosario I Corona6, Norma I Rodríguez-Malavé3, Ji-Hei Seo7, Emily Adler8, Simon G Coetzee3, Felipe Segato9, Marcos A S Fonseca9, Christopher I Amos10, Michael E Carney11, Georgia Chenevix-Trench12, Jiyeob Choi13, Jennifer A Doherty14, Weihua Jia15, Gang J Jin16, Byoung-Gie Kim17, Nhu D Le18, Juyeon Lee19, Lian Li2, Boon K Lim20, Noor A Adenan20, Mika Mizuno21, Boyoung Park22, Celeste L Pearce23, Kang Shan24, Yongyong Shi25, Xiao-Ou Shu26, Weiva Sieh27, Pamela J Thompson28, Lynne R Wilkens29, Qingyi Wei30, Yin L Woo20, Li Yan31, Beth Y Karlan32, Matthew L Freedman7, Houtan Noushmehr33, Ellen L Goode34, Andrew Berchuck35, Thomas A Sellers36, Soo-Hwang Teo37, Wei Zheng26, Keitaro Matsuo38, Sue Park13, Kexin Chen2, Paul D P Pharoah39, Simon A Gayther3, Marc T Goodman40. 1. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: kate.lawrenson@cshs.org. 2. National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China. 3. Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK. 5. Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, USA; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA. 6. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA; Center for Bioinformatics and Functional Genomics, Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 8. Department of Preventive Medicine, University of Southern California, Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA, USA. 9. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Brazil. 10. Institute for Clinical and Translational Research, Department of Medicine, Baylor School of Medicine, Houston,TX, USA. 11. Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. 12. Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD 4006, Australia. 13. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Department of Biomedical Science, Graduate School, Seoul National University, Seoul, Republic of Korea. 14. Jon M. and Karen Huntsman Endowed Associate Professor in Cancer Research Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, USA. 15. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China. 16. ShanghaiBio Corporation, Shanghai, China; CloudHealth Genomics Ltd, Shanghai, China. 17. Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Republic of Korea. 18. Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada. 19. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Science, Graduate School, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Republic of Korea. 20. The Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 21. Department of Gynecological Oncology, Aichi Cancer Center Hospital, Japan. 22. Department of Preventive Medicine, College of Medicine, Hanyang, Seoul, Republic of Korea. 23. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. 24. Department of Obstetrics and Gynaecology,Hebei Medical University, Fourth Hospital, Shijiazhuang, China. 25. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. 26. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA. 27. Department of Population Health Science and Policy, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 28. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 29. Cancer Epidemiology Program, University of Hawaii Cancer Center, HI, USA. 30. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA. 31. Department of Molecular Biology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China. 32. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, USA. 33. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Brazil; Department of Neurosurgery, Henry Ford Health System, Detroit, MI, USA. 34. Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA. 35. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA. 36. Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA. 37. Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia. 38. Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Japan. 39. Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK. 40. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract
OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7). CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.
OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7). CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.
Authors: P Lichtenstein; N V Holm; P K Verkasalo; A Iliadou; J Kaprio; M Koskenvuo; E Pukkala; A Skytthe; K Hemminki Journal: N Engl J Med Date: 2000-07-13 Impact factor: 91.245
Authors: Zhenfeng Duan; Rosemary Foster; Debra A Bell; Jennifer Mahoney; Kathryn Wolak; Ami Vaidya; Constanze Hampel; Hang Lee; Michael V Seiden Journal: Clin Cancer Res Date: 2006-09-01 Impact factor: 12.531
Authors: Ellen L Goode; Georgia Chenevix-Trench; Honglin Song; Susan J Ramus; Maria Notaridou; Kate Lawrenson; Martin Widschwendter; Robert A Vierkant; Melissa C Larson; Susanne K Kjaer; Michael J Birrer; Andrew Berchuck; Joellen Schildkraut; Ian Tomlinson; Lambertus A Kiemeney; Linda S Cook; Jacek Gronwald; Montserrat Garcia-Closas; Martin E Gore; Ian Campbell; Alice S Whittemore; Rebecca Sutphen; Catherine Phelan; Hoda Anton-Culver; Celeste Leigh Pearce; Diether Lambrechts; Mary Anne Rossing; Jenny Chang-Claude; Kirsten B Moysich; Marc T Goodman; Thilo Dörk; Heli Nevanlinna; Roberta B Ness; Thorunn Rafnar; Claus Hogdall; Estrid Hogdall; Brooke L Fridley; Julie M Cunningham; Weiva Sieh; Valerie McGuire; Andrew K Godwin; Daniel W Cramer; Dena Hernandez; Douglas Levine; Karen Lu; Edwin S Iversen; Rachel T Palmieri; Richard Houlston; Anne M van Altena; Katja K H Aben; Leon F A G Massuger; Angela Brooks-Wilson; Linda E Kelemen; Nhu D Le; Anna Jakubowska; Jan Lubinski; Krzysztof Medrek; Anne Stafford; Douglas F Easton; Jonathan Tyrer; Kelly L Bolton; Patricia Harrington; Diana Eccles; Ann Chen; Ashley N Molina; Barbara N Davila; Hector Arango; Ya-Yu Tsai; Zhihua Chen; Harvey A Risch; John McLaughlin; Steven A Narod; Argyrios Ziogas; Wendy Brewster; Aleksandra Gentry-Maharaj; Usha Menon; Anna H Wu; Daniel O Stram; Malcolm C Pike; Jonathan Beesley; Penelope M Webb; Xiaoqing Chen; Arif B Ekici; Falk C Thiel; Matthias W Beckmann; Hannah Yang; Nicolas Wentzensen; Jolanta Lissowska; Peter A Fasching; Evelyn Despierre; Frederic Amant; Ignace Vergote; Jennifer Doherty; Rebecca Hein; Shan Wang-Gohrke; Galina Lurie; Michael E Carney; Pamela J Thompson; Ingo Runnebaum; Peter Hillemanns; Matthias Dürst; Natalia Antonenkova; Natalia Bogdanova; Arto Leminen; Ralf Butzow; Tuomas Heikkinen; Kari Stefansson; Patrick Sulem; Sören Besenbacher; Thomas A Sellers; Simon A Gayther; Paul D P Pharoah Journal: Nat Genet Date: 2010-09-19 Impact factor: 38.330
Authors: Ko-Hui Tung; Marc T Goodman; Anna H Wu; Katharine McDuffie; Lynne R Wilkens; Laurence N Kolonel; Abraham M Y Nomura; Keith Y Terada; Michael E Carney; Leslie H Sobin Journal: Am J Epidemiol Date: 2003-10-01 Impact factor: 4.897
Authors: Maya Ghoussaini; Honglin Song; Thibaud Koessler; Ali Amin Al Olama; Zsofia Kote-Jarai; Kristy E Driver; Karen A Pooley; Susan J Ramus; Susanne Krüger Kjaer; Estrid Hogdall; Richard A DiCioccio; Alice S Whittemore; Simon A Gayther; Graham G Giles; Michelle Guy; Stephen M Edwards; Jonathan Morrison; Jenny L Donovan; Freddie C Hamdy; David P Dearnaley; Audrey T Ardern-Jones; Amanda L Hall; Lynne T O'Brien; Beatrice N Gehr-Swain; Rosemary A Wilkinson; Paul M Brown; John L Hopper; David E Neal; Paul D P Pharoah; Bruce A J Ponder; Rosalind A Eeles; Douglas F Easton; Alison M Dunning Journal: J Natl Cancer Inst Date: 2008-06-24 Impact factor: 13.506
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Authors: Ani Manichaikul; Lauren C Peres; Xin-Qun Wang; Mollie E Barnard; Deanna Chyn; Xin Sheng; Zhaohui Du; Jonathan Tyrer; Joseph Dennis; Ann G Schwartz; Michele L Cote; Edward Peters; Patricia G Moorman; Melissa Bondy; Jill S Barnholtz-Sloan; Paul Terry; Anthony J Alberg; Elisa V Bandera; Ellen Funkhouser; Anna H Wu; Celeste Leigh Pearce; Malcom Pike; Veronica Wendy Setiawan; Christopher A Haiman; Julie R Palmer; Loic LeMarchand; Lynne R Wilkens; Andrew Berchuck; Jennifer A Doherty; Francesmary Modugno; Roberta Ness; Kirsten Moysich; Beth Y Karlan; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Kate Lawrenson; Simon Gayther; Thomas A Sellers; Paul Pharoah; Joellen M Schildkraut Journal: Int J Cancer Date: 2019-10-08 Impact factor: 7.316
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