Katie M O'Brien1, Stephen R Cole, Lawrence S Engel, Jeannette T Bensen, Charles Poole, Amy H Herring, Robert C Millikan. 1. Authors' Affiliations: Department of Epidemiology, University of North Carolina Gillings School of Global Public Health; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill; and Department of Biostatistics and Carolina Population Center, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina.
Abstract
BACKGROUND: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study. METHODS: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6. RESULTS: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER- disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1. CONCLUSION AND IMPACT: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. .
BACKGROUND: Gene expression analyses indicate that breast cancer is a heterogeneous disease with at least five immunohistologic subtypes. Despite growing evidence that these subtypes are etiologically and prognostically distinct, few studies have investigated whether they have divergent genetic risk factors. To help fill in this gap in our understanding, we examined associations between breast cancer subtypes and previously established susceptibility loci among white and African-American women in the Carolina Breast Cancer Study. METHODS: We used Bayesian polytomous logistic regression to estimate ORs and 95% posterior intervals for the association between each of 78 single nucleotide polymorphisms (SNP) and five breast cancer subtypes. Subtypes were defined using five immunohistochemical markers: estrogen receptors (ER), progesterone receptors (PR), humanepidermal growth factor receptors 1 and 2 (HER1/2), and cytokeratin (CK) 5/6. RESULTS: Several SNPs in TNRC9/TOX3 were associated with luminal A (ER/PR+, HER2-) or basal-like breast cancer (ER-, PR-, HER2-, HER1, or CK 5/6+), and one SNP (rs3104746) was associated with both. SNPs in FGFR2 were associated with luminal A, luminal B (ER/PR+, HER2+), or HER2+/ER- disease, but none were associated with basal-like disease. We also observed subtype differences in the effects of SNPs in 2q35, 4p, TLR1, MAP3K1, ESR1, CDKN2A/B, ANKRD16, and ZM1Z1. CONCLUSION AND IMPACT: We found evidence that genetic risk factors for breast cancer vary by subtype and further clarified the role of several key susceptibility genes. .
Authors: Mia M Gaudet; Michael F Press; Robert W Haile; Charles F Lynch; Sally L Glaser; Joellen Schildkraut; Marilie D Gammon; W Douglas Thompson; Jonine L Bernstein Journal: Breast Cancer Res Treat Date: 2011-06-11 Impact factor: 4.872
Authors: Edith A Perez; Edward H Romond; Vera J Suman; Jong-Hyeon Jeong; Nancy E Davidson; Charles E Geyer; Silvana Martino; Eleftherios P Mamounas; Peter A Kaufman; Norman Wolmark Journal: J Clin Oncol Date: 2011-07-18 Impact factor: 44.544
Authors: Daniele Campa; Rudolf Kaaks; Loïc Le Marchand; Christopher A Haiman; Ruth C Travis; Christine D Berg; Julie E Buring; Stephen J Chanock; W Ryan Diver; Lucie Dostal; Agnes Fournier; Susan E Hankinson; Brian E Henderson; Robert N Hoover; Claudine Isaacs; Mattias Johansson; Laurence N Kolonel; Peter Kraft; I-Min Lee; Catherine A McCarty; Kim Overvad; Salvatore Panico; Petra H M Peeters; Elio Riboli; Maria José Sanchez; Fredrick R Schumacher; Guri Skeie; Daniel O Stram; Michael J Thun; Dimitrios Trichopoulos; Shumin Zhang; Regina G Ziegler; David J Hunter; Sara Lindström; Federico Canzian Journal: J Natl Cancer Inst Date: 2011-07-26 Impact factor: 13.506
Authors: Annegien Broeks; Marjanka K Schmidt; Mark E Sherman; Fergus J Couch; John L Hopper; Gillian S Dite; Carmel Apicella; Letitia D Smith; Fleur Hammet; Melissa C Southey; Laura J Van 't Veer; Renate de Groot; Vincent T H B M Smit; Peter A Fasching; Matthias W Beckmann; Sebastian Jud; Arif B Ekici; Arndt Hartmann; Alexander Hein; Ruediger Schulz-Wendtland; Barbara Burwinkel; Frederik Marme; Andreas Schneeweiss; Hans-Peter Sinn; Christof Sohn; Sandrine Tchatchou; Stig E Bojesen; Børge G Nordestgaard; Henrik Flyger; David D Ørsted; Diljit Kaur-Knudsen; Roger L Milne; Jose I Arias Pérez; Pilar Zamora; Primitiva Menéndez Rodríguez; Javier Benítez; Hiltrud Brauch; Christina Justenhoven; Yon-Dschun Ko; Ute Hamann; Hans-Peter Fischer; Thomas Brüning; Beate Pesch; Jenny Chang-Claude; Shan Wang-Gohrke; Michael Bremer; Johann H Karstens; Peter Hillemanns; Thilo Dörk; Heli A Nevanlinna; Tuomas Heikkinen; Päivi Heikkilä; Carl Blomqvist; Kristiina Aittomäki; Kirsimari Aaltonen; Annika Lindblom; Sara Margolin; Arto Mannermaa; Veli-Matti Kosma; Jaana M Kauppinen; Vesa Kataja; Päivi Auvinen; Matti Eskelinen; Ylermi Soini; Georgia Chenevix-Trench; Amanda B Spurdle; Jonathan Beesley; Xiaoqing Chen; Helene Holland; Diether Lambrechts; Bart Claes; Thijs Vandorpe; Patrick Neven; Hans Wildiers; Dieter Flesch-Janys; Rebecca Hein; Thomas Löning; Matthew Kosel; Zachary S Fredericksen; Xianshu Wang; Graham G Giles; Laura Baglietto; Gianluca Severi; Catriona McLean; Christopher A Haiman; Brian E Henderson; Loic Le Marchand; Laurence N Kolonel; Grethe Grenaker Alnæs; Vessela Kristensen; Anne-Lise Børresen-Dale; David J Hunter; Susan E Hankinson; Irene L Andrulis; Anna Marie Mulligan; Frances P O'Malley; Peter Devilee; Petra E A Huijts; Rob A E M Tollenaar; Christi J Van Asperen; Caroline S Seynaeve; Stephen J Chanock; Jolanta Lissowska; Louise Brinton; Beata Peplonska; Jonine Figueroa; Xiaohong R Yang; Maartje J Hooning; Antoinette Hollestelle; Rogier A Oldenburg; Agnes Jager; Mieke Kriege; Bahar Ozturk; Geert J L H van Leenders; Per Hall; Kamila Czene; Keith Humphreys; Jianjun Liu; Angela Cox; Daniel Connley; Helen E Cramp; Simon S Cross; Sabapathy P Balasubramanian; Malcolm W R Reed; Alison M Dunning; Douglas F Easton; Manjeet K Humphreys; Carlos Caldas; Fiona Blows; Kristy Driver; Elena Provenzano; Jan Lubinski; Anna Jakubowska; Tomasz Huzarski; Tomasz Byrski; Cezary Cybulski; Bohdan Gorski; Jacek Gronwald; Paul Brennan; Suleeporn Sangrajrang; Valerie Gaborieau; Chen-Yang Shen; Chia-Ni Hsiung; Jyh-Cherng Yu; Shou-Tung Chen; Giu-Cheng Hsu; Ming-Feng Hou; Chiun-Sheng Huang; Hoda Anton-Culver; Argyrios Ziogas; Paul D P Pharoah; Montserrat Garcia-Closas Journal: Hum Mol Genet Date: 2011-05-19 Impact factor: 6.150
Authors: Martha L Slattery; Kathy B Baumgartner; Anna R Giuliano; Tim Byers; Jennifer S Herrick; Roger K Wolff Journal: Breast Cancer Res Treat Date: 2011-04-08 Impact factor: 4.872
Authors: Kristen N Stevens; Celine M Vachon; Adam M Lee; Susan Slager; Timothy Lesnick; Curtis Olswold; Peter A Fasching; Penelope Miron; Diana Eccles; Jane E Carpenter; Andrew K Godwin; Christine Ambrosone; Robert Winqvist; Hiltrud Brauch; Marjanka K Schmidt; Angela Cox; Simon S Cross; Elinor Sawyer; Arndt Hartmann; Matthias W Beckmann; Rüdiger Schulz-Wendtland; Arif B Ekici; William J Tapper; Susan M Gerty; Lorraine Durcan; Nikki Graham; Rebecca Hein; Stephan Nickels; Dieter Flesch-Janys; Judith Heinz; Hans-Peter Sinn; Irene Konstantopoulou; Florentia Fostira; Dimitrios Pectasides; Athanasios M Dimopoulos; George Fountzilas; Christine L Clarke; Rosemary Balleine; Janet E Olson; Zachary Fredericksen; Robert B Diasio; Harsh Pathak; Eric Ross; JoEllen Weaver; Thomas Rüdiger; Asta Försti; Thomas Dünnebier; Foluso Ademuyiwa; Swati Kulkarni; Katri Pylkäs; Arja Jukkola-Vuorinen; Yon-Dschun Ko; Erik Van Limbergen; Hilde Janssen; Julian Peto; Olivia Fletcher; Graham G Giles; Laura Baglietto; Senno Verhoef; Ian Tomlinson; Veli-Matti Kosma; Jonathan Beesley; Dario Greco; Carl Blomqvist; Astrid Irwanto; Jianjun Liu; Fiona M Blows; Sarah-Jane Dawson; Sara Margolin; Arto Mannermaa; Nicholas G Martin; Grant W Montgomery; Diether Lambrechts; Isabel dos Santos Silva; Gianluca Severi; Ute Hamann; Paul Pharoah; Douglas F Easton; Jenny Chang-Claude; Drakoulis Yannoukakos; Heli Nevanlinna; Xianshu Wang; Fergus J Couch Journal: Cancer Res Date: 2011-08-15 Impact factor: 12.701
Authors: Min Shi; Katie M O'Brien; Dale P Sandler; Jack A Taylor; Dmitri V Zaykin; Clarice R Weinberg Journal: Breast Cancer Res Treat Date: 2016-11-15 Impact factor: 4.872
Authors: Sarah J Nyante; Marilie D Gammon; Jay S Kaufman; Jeannette T Bensen; Dan Yu Lin; Jill S Barnholtz-Sloan; Yijuan Hu; Qianchuan He; Jingchun Luo; Robert C Millikan Journal: Cancer Causes Control Date: 2014-11-25 Impact factor: 2.506
Authors: Marc A Emerson; Katherine E Reeder-Hayes; Heather J Tipaldos; Mary E Bell; Marina R Sweeney; Lisa A Carey; H Shelton Earp; Andrew F Olshan; Melissa A Troester Journal: Curr Breast Cancer Rep Date: 2020-05-14
Authors: Nicole Mavingire; Petreena Campbell; Jonathan Wooten; Joyce Aja; Melissa B Davis; Andrea Loaiza-Perez; Eileen Brantley Journal: Cancer Lett Date: 2020-12-09 Impact factor: 8.679