BACKGROUND: Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information. MATERIALS AND METHODS: We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms for 1,145 postmenopausal women with invasive breast cancer (7,711 person-years at risk) from the Nurses' Health Study scanned in the Cancer Genetic Markers of Susceptibility initiative. We genotyped the 10 most statistically significant loci (most significant single-nucleotide polymorphism located in ARHGAP10; P = 2.28 x 10(-7)) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. RESULTS: None of the loci replicated in the SEARCH study (all P > 0.10). Assuming a minimum of 10 associated loci, the power to detect at least one with a minor allele frequency of 0.2 conferring a relative hazard of 2.0 at genome-wide significance (P = 5 x 10(-8)) was 99%. CONCLUSION: We did not identify any common germline variants associated with breast cancer survival overall. IMPACT: Our data suggest that it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (hazard ratio >2). Instead, it is plausible that common variants associated with survival could be specific to tumor subtypes or treatment approaches. New studies, sufficiently powered, are needed to discover new regions associated with survival overall or by subtype or treatment subgroups.
BACKGROUND: Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information. MATERIALS AND METHODS: We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms for 1,145 postmenopausal women with invasive breast cancer (7,711 person-years at risk) from the Nurses' Health Study scanned in the Cancer Genetic Markers of Susceptibility initiative. We genotyped the 10 most statistically significant loci (most significant single-nucleotide polymorphism located in ARHGAP10; P = 2.28 x 10(-7)) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. RESULTS: None of the loci replicated in the SEARCH study (all P > 0.10). Assuming a minimum of 10 associated loci, the power to detect at least one with a minor allele frequency of 0.2 conferring a relative hazard of 2.0 at genome-wide significance (P = 5 x 10(-8)) was 99%. CONCLUSION: We did not identify any common germline variants associated with breast cancer survival overall. IMPACT: Our data suggest that it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (hazard ratio >2). Instead, it is plausible that common variants associated with survival could be specific to tumor subtypes or treatment approaches. New studies, sufficiently powered, are needed to discover new regions associated with survival overall or by subtype or treatment subgroups.
Authors: A Naderi; A E Teschendorff; N L Barbosa-Morais; S E Pinder; A R Green; D G Powe; J F R Robertson; S Aparicio; I O Ellis; J D Brenton; C Caldas Journal: Oncogene Date: 2006-08-28 Impact factor: 9.867
Authors: David J Hunter; Peter Kraft; Kevin B Jacobs; David G Cox; Meredith Yeager; Susan E Hankinson; Sholom Wacholder; Zhaoming Wang; Robert Welch; Amy Hutchinson; Junwen Wang; Kai Yu; Nilanjan Chatterjee; Nick Orr; Walter C Willett; Graham A Colditz; Regina G Ziegler; Christine D Berg; Saundra S Buys; Catherine A McCarty; Heather Spencer Feigelson; Eugenia E Calle; Michael J Thun; Richard B Hayes; Margaret Tucker; Daniela S Gerhard; Joseph F Fraumeni; Robert N Hoover; Gilles Thomas; Stephen J Chanock Journal: Nat Genet Date: 2007-05-27 Impact factor: 38.330
Authors: Miriam S Udler; Elizabeth M Azzato; Catherine S Healey; Shahana Ahmed; Karen A Pooley; David Greenberg; Mitul Shah; Andrew E Teschendorff; Carlos Caldas; Alison M Dunning; Elaine A Ostrander; Neil E Caporaso; Douglas Easton; Paul D Pharoah Journal: Int J Cancer Date: 2009-12-01 Impact factor: 7.396
Authors: Laura J van 't Veer; Hongyue Dai; Marc J van de Vijver; Yudong D He; Augustinus A M Hart; Mao Mao; Hans L Peterse; Karin van der Kooy; Matthew J Marton; Anke T Witteveen; George J Schreiber; Ron M Kerkhoven; Chris Roberts; Peter S Linsley; René Bernards; Stephen H Friend Journal: Nature Date: 2002-01-31 Impact factor: 49.962
Authors: T Sørlie; C M Perou; R Tibshirani; T Aas; S Geisler; H Johnsen; T Hastie; M B Eisen; M van de Rijn; S S Jeffrey; T Thorsen; H Quist; J C Matese; P O Brown; D Botstein; P E Lønning; A L Børresen-Dale Journal: Proc Natl Acad Sci U S A Date: 2001-09-11 Impact factor: 11.205
Authors: Marc J van de Vijver; Yudong D He; Laura J van't Veer; Hongyue Dai; Augustinus A M Hart; Dorien W Voskuil; George J Schreiber; Johannes L Peterse; Chris Roberts; Matthew J Marton; Mark Parrish; Douwe Atsma; Anke Witteveen; Annuska Glas; Leonie Delahaye; Tony van der Velde; Harry Bartelink; Sjoerd Rodenhuis; Emiel T Rutgers; Stephen H Friend; René Bernards Journal: N Engl J Med Date: 2002-12-19 Impact factor: 91.245
Authors: Rainer Fagerholm; Barbara Hofstetter; Johanna Tommiska; Kirsimari Aaltonen; Radek Vrtel; Kirsi Syrjäkoski; Anne Kallioniemi; Outi Kilpivaara; Arto Mannermaa; Veli-Matti Kosma; Matti Uusitupa; Matti Eskelinen; Vesa Kataja; Kristiina Aittomäki; Karl von Smitten; Päivi Heikkilä; Jiri Lukas; Kaija Holli; Jirina Bartkova; Carl Blomqvist; Jiri Bartek; Heli Nevanlinna Journal: Nat Genet Date: 2008-05-30 Impact factor: 38.330
Authors: Gilles Thomas; Kevin B Jacobs; Peter Kraft; Meredith Yeager; Sholom Wacholder; David G Cox; Susan E Hankinson; Amy Hutchinson; Zhaoming Wang; Kai Yu; Nilanjan Chatterjee; Montserrat Garcia-Closas; Jesus Gonzalez-Bosquet; Ludmila Prokunina-Olsson; Nick Orr; Walter C Willett; Graham A Colditz; Regina G Ziegler; Christine D Berg; Saundra S Buys; Catherine A McCarty; Heather Spencer Feigelson; Eugenia E Calle; Michael J Thun; Ryan Diver; Ross Prentice; Rebecca Jackson; Charles Kooperberg; Rowan Chlebowski; Jolanta Lissowska; Beata Peplonska; Louise A Brinton; Alice Sigurdson; Michele Doody; Parveen Bhatti; Bruce H Alexander; Julie Buring; I-Min Lee; Lars J Vatten; Kristian Hveem; Merethe Kumle; Richard B Hayes; Margaret Tucker; Daniela S Gerhard; Joseph F Fraumeni; Robert N Hoover; Stephen J Chanock; David J Hunter Journal: Nat Genet Date: 2009-03-29 Impact factor: 38.330
Authors: Elizabeth M Azzato; Kristy E Driver; Fabienne Lesueur; Mitul Shah; David Greenberg; Douglas F Easton; Andrew E Teschendorff; Carlos Caldas; Neil E Caporaso; Paul D P Pharoah Journal: Breast Cancer Res Date: 2008-05-28 Impact factor: 6.466
Authors: Xinyi Lin; Tianxi Cai; Michael C Wu; Qian Zhou; Geoffrey Liu; David C Christiani; Xihong Lin Journal: Genet Epidemiol Date: 2011-08-04 Impact factor: 2.135
Authors: Kathryn S Higginbotham; Joan P Breyer; Kate M McReynolds; Kevin M Bradley; Peggy A Schuyler; W Dale Plummer; Marcia E Freudenthal; Amy Trentham-Dietz; Polly A Newcomb; Fritz F Parl; Melinda E Sanders; David L Page; Kathleen M Egan; William D Dupont; Jeffrey R Smith Journal: Cancer Epidemiol Biomarkers Prev Date: 2012-07-17 Impact factor: 4.254
Authors: Alexei Vazquez; Diptee Kulkarni; Lukasz F Grochola; Gareth L Bond; Nicola Barnard; Deborah Toppmeyer; Arnold J Levine; Kim M Hirshfield Journal: Int J Cancer Date: 2011-05-15 Impact factor: 7.396
Authors: Maral Jamshidi; Marjanka K Schmidt; Thilo Dörk; Montserrat Garcia-Closas; Tuomas Heikkinen; Sten Cornelissen; Alexandra J van den Broek; Peter Schürmann; Andreas Meyer; Tjoung-Won Park-Simon; Jonine Figueroa; Mark Sherman; Jolanta Lissowska; Garrett Teoh Hor Keong; Astrid Irwanto; Marko Laakso; Sampsa Hautaniemi; Kristiina Aittomäki; Carl Blomqvist; Jianjun Liu; Heli Nevanlinna Journal: Int J Cancer Date: 2012-10-25 Impact factor: 7.396