BACKGROUND: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. IMPACT: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.
BACKGROUND:Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. IMPACT: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed.
Authors: Prema Peethambaram; Brooke L Fridley; Robert A Vierkant; Melissa C Larson; Kimberly R Kalli; Elaine A Elliott; Ann L Oberg; Kristin L White; David N Rider; Gary L Keeney; Julie M Cunningham; Lynn C Hartmann; Ellen L Goode Journal: Int J Mol Epidemiol Genet Date: 2011-05-02
Authors: Ahmedin Jemal; Freddie Bray; Melissa M Center; Jacques Ferlay; Elizabeth Ward; David Forman Journal: CA Cancer J Clin Date: 2011-02-04 Impact factor: 508.702
Authors: Ellen L Goode; Georgia Chenevix-Trench; Lynn C Hartmann; Brooke L Fridley; Kimberly R Kalli; Robert A Vierkant; Melissa C Larson; Kristin L White; Gary L Keeney; Trynda N Oberg; Julie M Cunningham; Jonathan Beesley; Sharon E Johnatty; Xiaoqing Chen; Katelyn E Goodman; Sebastian M Armasu; David N Rider; Hugues Sicotte; Michele M Schmidt; Elaine A Elliott; Estrid Høgdall; Susanne Krüger Kjær; Peter A Fasching; Arif B Ekici; Diether Lambrechts; Evelyn Despierre; Claus Høgdall; Lene Lundvall; Beth Y Karlan; Jenny Gross; Robert Brown; Jeremy Chien; David J Duggan; Ya-Yu Tsai; Catherine M Phelan; Linda E Kelemen; Prema P Peethambaram; Joellen M Schildkraut; Vijayalakshmi Shridhar; Rebecca Sutphen; Fergus J Couch; Thomas A Sellers Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-07-01 Impact factor: 4.254
Authors: Ellen L Goode; Matthew J Maurer; Thomas A Sellers; Catherine M Phelan; Kimberly R Kalli; Brooke L Fridley; Robert A Vierkant; Sebastian M Armasu; Kristin L White; Gary L Keeney; William A Cliby; David N Rider; Linda E Kelemen; Monica B Jones; Prema P Peethambaram; Johnathan M Lancaster; Janet E Olson; Joellen M Schildkraut; Julie M Cunningham; Lynn C Hartmann Journal: Clin Cancer Res Date: 2010-01-26 Impact factor: 12.531
Authors: Paul D P Pharoah; Ya-Yu Tsai; Susan J Ramus; Catherine M Phelan; Ellen L Goode; Kate Lawrenson; Melissa Buckley; Brooke L Fridley; Jonathan P Tyrer; Howard Shen; Rachel Weber; Rod Karevan; Melissa C Larson; Honglin Song; Daniel C Tessier; François Bacot; Daniel Vincent; Julie M Cunningham; Joe Dennis; Ed Dicks; Katja K Aben; Hoda Anton-Culver; Natalia Antonenkova; Sebastian M Armasu; Laura Baglietto; Elisa V Bandera; Matthias W Beckmann; Michael J Birrer; Greg Bloom; Natalia Bogdanova; James D Brenton; Louise A Brinton; Angela Brooks-Wilson; Robert Brown; Ralf Butzow; Ian Campbell; Michael E Carney; Renato S Carvalho; Jenny Chang-Claude; Y Anne Chen; Zhihua Chen; Wong-Ho Chow; Mine S Cicek; Gerhard Coetzee; Linda S Cook; Daniel W Cramer; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Evelyn Despierre; Jennifer A Doherty; Thilo Dörk; Andreas du Bois; Matthias Dürst; Diana Eccles; Robert Edwards; Arif B Ekici; Peter A Fasching; David Fenstermacher; James Flanagan; Yu-Tang Gao; Montserrat Garcia-Closas; Aleksandra Gentry-Maharaj; Graham Giles; Anxhela Gjyshi; Martin Gore; Jacek Gronwald; Qi Guo; Mari K Halle; Philipp Harter; Alexander Hein; Florian Heitz; Peter Hillemanns; Maureen Hoatlin; Estrid Høgdall; Claus K Høgdall; Satoyo Hosono; Anna Jakubowska; Allan Jensen; Kimberly R Kalli; Beth Y Karlan; Linda E Kelemen; Lambertus A Kiemeney; Susanne Krüger Kjaer; Gottfried E Konecny; Camilla Krakstad; Jolanta Kupryjanczyk; Diether Lambrechts; Sandrina Lambrechts; Nhu D Le; Nathan Lee; Janet Lee; Arto Leminen; Boon Kiong Lim; Jolanta Lissowska; Jan Lubiński; Lene Lundvall; Galina Lurie; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R McLaughlin; Usha Menon; Francesmary Modugno; Kirsten B Moysich; Toru Nakanishi; Steven A Narod; Roberta B Ness; Heli Nevanlinna; Stefan Nickels; Houtan Noushmehr; Kunle Odunsi; Sara Olson; Irene Orlow; James Paul; Tanja Pejovic; Liisa M Pelttari; Jenny Permuth-Wey; Malcolm C Pike; Elizabeth M Poole; Xiaotao Qu; Harvey A Risch; Lorna Rodriguez-Rodriguez; Mary Anne Rossing; Anja Rudolph; Ingo Runnebaum; Iwona K Rzepecka; Helga B Salvesen; Ira Schwaab; Gianluca Severi; Hui Shen; Vijayalakshmi Shridhar; Xiao-Ou Shu; Weiva Sieh; Melissa C Southey; Paul Spellman; Kazuo Tajima; Soo-Hwang Teo; Kathryn L Terry; Pamela J Thompson; Agnieszka Timorek; Shelley S Tworoger; Anne M van Altena; David van den Berg; Ignace Vergote; Robert A Vierkant; Allison F Vitonis; Shan Wang-Gohrke; Nicolas Wentzensen; Alice S Whittemore; Elisabeth Wik; Boris Winterhoff; Yin Ling Woo; Anna H Wu; Hannah P Yang; Wei Zheng; Argyrios Ziogas; Famida Zulkifli; Marc T Goodman; Per Hall; Douglas F Easton; Celeste L Pearce; Andrew Berchuck; Georgia Chenevix-Trench; Edwin Iversen; Alvaro N A Monteiro; Simon A Gayther; Joellen M Schildkraut; Thomas A Sellers Journal: Nat Genet Date: 2013-04 Impact factor: 38.330
Authors: Stacey J Winham; Ailith Pirie; Yian Ann Chen; Melissa C Larson; Zachary C Fogarty; Madalene A Earp; Hoda Anton-Culver; Elisa V Bandera; Daniel Cramer; Jennifer A Doherty; Marc T Goodman; Jacek Gronwald; Beth Y Karlan; Susanne K Kjaer; Douglas A Levine; Usha Menon; Roberta B Ness; Celeste L Pearce; Tanja Pejovic; Mary Anne Rossing; Nicolas Wentzensen; Yukie T Bean; Maria Bisogna; Louise A Brinton; Michael E Carney; Julie M Cunningham; Cezary Cybulski; Anna deFazio; Ed M Dicks; Robert P Edwards; Simon A Gayther; Aleksandra Gentry-Maharaj; Martin Gore; Edwin S Iversen; Allan Jensen; Sharon E Johnatty; Jenny Lester; Hui-Yi Lin; Jolanta Lissowska; Jan Lubinski; Janusz Menkiszak; Francesmary Modugno; Kirsten B Moysich; Irene Orlow; Malcolm C Pike; Susan J Ramus; Honglin Song; Kathryn L Terry; Pamela J Thompson; Jonathan P Tyrer; David J van den Berg; Robert A Vierkant; Allison F Vitonis; Christine Walsh; Lynne R Wilkens; Anna H Wu; Hannah Yang; Argyrios Ziogas; Andrew Berchuck; Georgia Chenevix-Trench; Joellen M Schildkraut; Jennifer Permuth-Wey; Catherine M Phelan; Paul D P Pharoah; Brooke L Fridley; Thomas A Sellers; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-01-08 Impact factor: 4.254
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Sandra Orsulic; Ana Osorio; Laura Ottini; James Paul; Celeste L Pearce; Inge Sokilde Pedersen; Bernard Peissel; Tanja Pejovic; Liisa M Pelttari; Jo Perkins; Jenny Permuth-Wey; Paolo Peterlongo; Julian Peto; Catherine M Phelan; Kelly-Anne Phillips; Marion Piedmonte; Malcolm C Pike; Radka Platte; Joanna Plisiecka-Halasa; Elizabeth M Poole; Bruce Poppe; Katri Pylkäs; Paolo Radice; Susan J Ramus; Timothy R Rebbeck; Malcolm W R Reed; Gad Rennert; Harvey A Risch; Mark Robson; Gustavo C Rodriguez; Atocha Romero; Mary Anne Rossing; Joseph H Rothstein; Anja Rudolph; Ingo Runnebaum; Ritu Salani; Helga B Salvesen; Elinor J Sawyer; Joellen M Schildkraut; Marjanka K Schmidt; Rita K Schmutzler; Andreas Schneeweiss; Minouk J Schoemaker; Michael G Schrauder; Fredrick Schumacher; Ira Schwaab; Giulietta Scuvera; Thomas A Sellers; Gianluca Severi; Caroline M Seynaeve; Mitul Shah; Martha Shrubsole; Nadeem Siddiqui; Weiva Sieh; Jacques Simard; Christian F Singer; Olga M Sinilnikova; Dominiek Smeets; Christof Sohn; Maria Soller; Honglin Song; Penny Soucy; Melissa C Southey; Christa Stegmaier; Dominique Stoppa-Lyonnet; Lara Sucheston; Anthony Swerdlow; Ingvild L Tangen; Muy-Kheng Tea; Manuel R Teixeira; Kathryn L Terry; Mary Beth Terry; Mads Thomassen; Pamela J Thompson; Laima Tihomirova; Marc Tischkowitz; Amanda Ewart Toland; Rob A E M Tollenaar; Ian Tomlinson; Diana Torres; Thérèse Truong; Helen Tsimiklis; Nadine Tung; Shelley S Tworoger; Jonathan P Tyrer; Celine M Vachon; Laura J Van 't Veer; Anne M van Altena; C J Van Asperen; David van den Berg; Ans M W van den Ouweland; Helena C van Doorn; Els Van Nieuwenhuysen; Elizabeth J van Rensburg; Ignace Vergote; Senno Verhoef; Robert A Vierkant; Joseph Vijai; Allison F Vitonis; Anna von Wachenfeldt; Christine Walsh; Qin Wang; Shan Wang-Gohrke; Barbara Wappenschmidt; Maren Weischer; Jeffrey N Weitzel; Caroline Weltens; Nicolas Wentzensen; Alice S Whittemore; Lynne R Wilkens; Robert Winqvist; Anna H Wu; Xifeng Wu; Hannah P Yang; Daniela Zaffaroni; M Pilar Zamora; 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Authors: Bridget Charbonneau; Kirsten B Moysich; Kimberly R Kalli; Ann L Oberg; Robert A Vierkant; Zachary C Fogarty; Matthew S Block; Matthew J Maurer; Krista M Goergen; Brooke L Fridley; Julie M Cunningham; David N Rider; Claudia Preston; Lynn C Hartmann; Kate Lawrenson; Chen Wang; Jonathan Tyrer; Honglin Song; Anna deFazio; Sharon E Johnatty; Jennifer A Doherty; Catherine M Phelan; Thomas A Sellers; Starr M Ramirez; Allison F Vitonis; Kathryn L Terry; David Van Den Berg; Malcolm C Pike; Anna H Wu; Andrew Berchuck; Aleksandra Gentry-Maharaj; Susan J Ramus; Brenda Diergaarde; Howard Shen; Allan Jensen; Janusz Menkiszak; Cezary Cybulski; Jan Lubiłski; Argyrios Ziogas; Joseph H Rothstein; Valerie McGuire; Weiva Sieh; Jenny Lester; Christine Walsh; Ignace Vergote; Sandrina Lambrechts; Evelyn Despierre; Montserrat Garcia-Closas; Hannah Yang; Louise A Brinton; Beata Spiewankiewicz; Iwona K Rzepecka; Agnieszka Dansonka-Mieszkowska; Petra Seibold; Anja Rudolph; Lisa E Paddock; Irene Orlow; Lene Lundvall; Sara H Olson; Claus K Hogdall; Ira Schwaab; Andreas du Bois; Philipp Harter; James M Flanagan; Robert Brown; James Paul; Arif B Ekici; Matthias W Beckmann; Alexander Hein; Diana Eccles; Galina Lurie; Laura E Hays; Yukie T Bean; Tanja Pejovic; Marc T Goodman; Ian Campbell; Peter A Fasching; Gottfried Konecny; Stanley B Kaye; Florian Heitz; Estrid Hogdall; Elisa V Bandera; Jenny Chang-Claude; Jolanta Kupryjanczyk; Nicolas Wentzensen; Diether Lambrechts; Beth Y Karlan; Alice S Whittemore; Hoda Anton Culver; Jacek Gronwald; Douglas A Levine; Susanne K Kjaer; Usha Menon; Joellen M Schildkraut; Celeste Leigh Pearce; Daniel W Cramer; Mary Anne Rossing; Georgia Chenevix-Trench; Paul D P Pharoah; Simon A Gayther; Roberta B Ness; Kunle Odunsi; Lara E Sucheston; Keith L Knutson; Ellen L Goode Journal: Cancer Immunol Res Date: 2014-01-27 Impact factor: 11.151
Authors: Sandrina Lambrechts; Diether Lambrechts; Evelyn Despierre; Els Van Nieuwenhuysen; Dominiek Smeets; Philip R Debruyne; Vincent Renard; Philippe Vroman; Daisy Luyten; Patrick Neven; Frédéric Amant; Karin Leunen; Ignace Vergote Journal: BMC Pharmacol Toxicol Date: 2015-02-27 Impact factor: 2.483
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Authors: Matthew S Block; Bridget Charbonneau; Robert A Vierkant; Zachary Fogarty; William R Bamlet; Paul D P Pharoah; Mary Anne Rossing; Daniel Cramer; Celeste Leigh Pearce; Joellen Schildkraut; Usha Menon; Susanne K Kjaer; Douglas A Levine; Jacek Gronwald; Hoda Anton Culver; Alice S Whittemore; Beth Y Karlan; Diether Lambrechts; Nicolas Wentzensen; Jolanta Kupryjanczyk; Jenny Chang-Claude; Elisa V Bandera; Estrid Hogdall; Florian Heitz; Stanley B Kaye; Peter A Fasching; Ian Campbell; Marc T Goodman; Tanja Pejovic; Yukie T Bean; Laura E Hays; Galina Lurie; Diana Eccles; Alexander Hein; Matthias W Beckmann; Arif B Ekici; James Paul; Robert Brown; James M Flanagan; Philipp Harter; Andreas du Bois; Ira Schwaab; Claus K Hogdall; Lene Lundvall; Sara H Olson; Irene Orlow; Lisa E Paddock; Anja Rudolph; Ursula Eilber; Agnieszka Dansonka-Mieszkowska; Iwona K Rzepecka; Izabela Ziolkowska-Seta; Louise A Brinton; Hannah Yang; Montserrat Garcia-Closas; Evelyn Despierre; Sandrina Lambrechts; Ignace Vergote; Christine S Walsh; Jenny Lester; Weiva Sieh; Valerie McGuire; Joseph H Rothstein; Argyrios Ziogas; Jan Lubiński; Cezary Cybulski; Janusz Menkiszak; Allan Jensen; Simon A Gayther; Susan J Ramus; Aleksandra Gentry-Maharaj; Andrew Berchuck; Anna H Wu; Malcolm C Pike; David Van Den Berg; Kathryn L Terry; Allison F Vitonis; Starr M Ramirez; David N Rider; Keith L Knutson; Thomas A Sellers; Catherine M Phelan; Jennifer A Doherty; Sharon E Johnatty; Anna deFazio; Honglin Song; Jonathan Tyrer; Kimberly R Kalli; Brooke L Fridley; Julie M Cunningham; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-04-16 Impact factor: 4.254
Authors: Brooke L Fridley; Taraswi M Ghosh; Alice Wang; Rama Raghavan; Junqiang Dai; Ellen L Goode; Jatinder K Lamba Journal: Front Genet Date: 2016-03-22 Impact factor: 4.599