Alice W Lee1, Claire Templeman2, Douglas A Stram1, Jonathan Beesley3, Jonathan Tyrer4, Andrew Berchuck5, Paul P Pharoah6, Georgia Chenevix-Trench3, Celeste Leigh Pearce7. 1. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 2. Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California. 3. Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 4. Department of Oncology and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom. 5. Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina. 6. Department of Oncology and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom; Department of Public Health and Primary Care and Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom. 7. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan. Electronic address: lpearce@umich.edu.
Abstract
OBJECTIVE: To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. DESIGN: Pooled genetic analysis. SETTING: University hospital. PATIENT(S): Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometriosis-associated genetic variation and ovarian cancer. RESULT(S): There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. CONCLUSION(S): By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
OBJECTIVE: To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. DESIGN: Pooled genetic analysis. SETTING: University hospital. PATIENT(S): Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometriosis-associated genetic variation and ovarian cancer. RESULT(S): There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. CONCLUSION(S): By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.
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: Bryan Howie; Christian Fuchsberger; Matthew Stephens; Jonathan Marchini; Gonçalo R Abecasis Journal: Nat Genet Date: 2012-07-22 Impact factor: 38.330
Authors: Kelly L Bolton; Jonathan Tyrer; Honglin Song; Susan J Ramus; Maria Notaridou; Chris Jones; Tanya Sher; Aleksandra Gentry-Maharaj; Eva Wozniak; Ya-Yu Tsai; Joanne Weidhaas; Daniel Paik; David J Van Den Berg; Daniel O Stram; Celeste Leigh Pearce; Anna H Wu; Wendy Brewster; Hoda Anton-Culver; Argyrios Ziogas; Steven A Narod; Douglas A Levine; Stanley B Kaye; Robert Brown; Jim Paul; James Flanagan; Weiva Sieh; Valerie McGuire; Alice S Whittemore; Ian Campbell; Martin E Gore; Jolanta Lissowska; Hanna P Yang; Krzysztof Medrek; Jacek Gronwald; Jan Lubinski; Anna Jakubowska; Nhu D Le; Linda S Cook; Linda E Kelemen; Angela Brooks-Wilson; Angela Brook-Wilson; Leon F A G Massuger; Lambertus A Kiemeney; Katja K H Aben; Anne M van Altena; Richard Houlston; Ian Tomlinson; Rachel T Palmieri; Patricia G Moorman; Joellen Schildkraut; Edwin S Iversen; Catherine Phelan; Robert A Vierkant; Julie M Cunningham; Ellen L Goode; Brooke L Fridley; Susan Kruger-Kjaer; Jan Blaeker; Estrid Hogdall; Claus Hogdall; Jenny Gross; Beth Y Karlan; Roberta B Ness; Robert P Edwards; Kunle Odunsi; Kirsten B Moyisch; Julie A Baker; Francesmary Modugno; Tuomas Heikkinenen; Ralf Butzow; Heli Nevanlinna; Arto Leminen; Natalia Bogdanova; Natalia Antonenkova; Thilo Doerk; Peter Hillemanns; Matthias Dürst; Ingo Runnebaum; Pamela J Thompson; Michael E Carney; Marc T Goodman; Galina Lurie; Shan Wang-Gohrke; Rebecca Hein; Jenny Chang-Claude; Mary Anne Rossing; Kara L Cushing-Haugen; Jennifer Doherty; Chu Chen; Thorunn Rafnar; Soren Besenbacher; Patrick Sulem; Kari Stefansson; Michael J Birrer; Kathryn L Terry; Dena Hernandez; Daniel W Cramer; Ignace Vergote; Frederic Amant; Diether Lambrechts; Evelyn Despierre; Peter A Fasching; Matthias W Beckmann; Falk C Thiel; Arif B Ekici; Xiaoqing Chen; Sharon E Johnatty; Penelope M Webb; Jonathan Beesley; Stephen Chanock; Montserrat Garcia-Closas; Tom Sellers; Douglas F Easton; Andrew Berchuck; Georgia Chenevix-Trench; Paul D P Pharoah; Simon A Gayther Journal: Nat Genet Date: 2010-09-19 Impact factor: 41.307
Authors: Dale R Nyholt; Siew-Kee Low; Carl A Anderson; Jodie N Painter; Satoko Uno; Andrew P Morris; Stuart MacGregor; Scott D Gordon; Anjali K Henders; Nicholas G Martin; John Attia; Elizabeth G Holliday; Mark McEvoy; Rodney J Scott; Stephen H Kennedy; Susan A Treloar; Stacey A Missmer; Sosuke Adachi; Kenichi Tanaka; Yusuke Nakamura; Krina T Zondervan; Hitoshi Zembutsu; Grant W Montgomery Journal: Nat Genet Date: 2012-10-28 Impact factor: 38.330
Authors: Laura A Laviolette; Kendra M Hodgkinson; Neha Minhas; Carol Perez-Iratxeta; Barbara C Vanderhyden Journal: Int J Cancer Date: 2014-02-25 Impact factor: 7.396
Authors: Alexis D Greene; Stephanie A Lang; Jessica A Kendziorski; Julie M Sroga-Rios; Thomas J Herzog; Katherine A Burns Journal: Reproduction Date: 2016-05-10 Impact factor: 3.906
Authors: Hyo K Park; Joellen M Schildkraut; Anthony J Alberg; Elisa V Bandera; Jill S Barnholtz-Sloan; Melissa Bondy; Sydnee Crankshaw; Ellen Funkhouser; Patricia G Moorman; Edward S Peters; Paul Terry; Frances Wang; Julie J Ruterbusch; Ann G Schwartz; Michele L Cote Journal: Cancer Causes Control Date: 2018-09-29 Impact factor: 2.506
Authors: Elizabeth M Poole; Wayne T Lin; Marina Kvaskoff; Immaculata De Vivo; Kathryn L Terry; Stacey A Missmer Journal: Cancer Causes Control Date: 2017-03-15 Impact factor: 2.506
Authors: Yi Yu-Rice; Seby L Edassery; Nicole Urban; Ingegerd Hellstrom; Karl Erik Hellstrom; Youping Deng; Yan Li; Judith L Luborsky Journal: Reproduction Date: 2016-12-13 Impact factor: 3.906
Authors: Sally Mortlock; Rosario I Corona; Pik Fang Kho; Paul Pharoah; Ji-Heui Seo; Matthew L Freedman; Simon A Gayther; Matthew T Siedhoff; Peter A W Rogers; Ronald Leuchter; Christine S Walsh; Ilana Cass; Beth Y Karlan; B J Rimel; Grant W Montgomery; Kate Lawrenson; Siddhartha P Kar Journal: Cell Rep Med Date: 2022-03-15