BACKGROUND: In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high-risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease-associated) mutations in non-white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing. METHODS: In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing. RESULTS: From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non-European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1-1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1-1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non-European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%-->5.9%), and women of African ancestry experienced the largest decline (58%). CONCLUSIONS: Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women.
BACKGROUND: In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high-risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease-associated) mutations in non-white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing. METHODS: In this cross-sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non-Ashkenazi Jewish women who underwent genetic testing. RESULTS: From 1996 to 2006, 46,276 women who met study criteria underwent DNA full-sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non-European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1-1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1-1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non-European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%-->5.9%), and women of African ancestry experienced the largest decline (58%). CONCLUSIONS: Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high-risk women.
Authors: Carol Smigal; Ahmedin Jemal; Elizabeth Ward; Vilma Cokkinides; Robert Smith; Holly L Howe; Michael Thun Journal: CA Cancer J Clin Date: 2006 May-Jun Impact factor: 508.702
Authors: Cynthia L Ogden; Margaret D Carroll; Lester R Curtin; Margaret A McDowell; Carolyn J Tabak; Katherine M Flegal Journal: JAMA Date: 2006-04-05 Impact factor: 56.272
Authors: Thomas S Frank; Amie M Deffenbaugh; Julia E Reid; Mark Hulick; Brian E Ward; Beth Lingenfelter; Kathi L Gumpper; Thomas Scholl; Sean V Tavtigian; Dmitry R Pruss; Gregory C Critchfield Journal: J Clin Oncol Date: 2002-03-15 Impact factor: 44.544
Authors: Kelly Metcalfe; Henry T Lynch; Parviz Ghadirian; Nadine Tung; Ivo Olivotto; Ellen Warner; Olufunmilayo I Olopade; Andrea Eisen; Barbara Weber; Jane McLennan; Ping Sun; William D Foulkes; Steven A Narod Journal: J Clin Oncol Date: 2004-06-15 Impact factor: 44.544
Authors: Olufunmilayo I Olopade; James D Fackenthal; Georgia Dunston; Michael A Tainsky; Francis Collins; Carolyn Whitfield-Broome Journal: Cancer Date: 2003-01-01 Impact factor: 6.860
Authors: Timothy R Rebbeck; Tara Friebel; Henry T Lynch; Susan L Neuhausen; Laura van 't Veer; Judy E Garber; Gareth R Evans; Steven A Narod; Claudine Isaacs; Ellen Matloff; Mary B Daly; Olufunmilayo I Olopade; Barbara L Weber Journal: J Clin Oncol Date: 2004-02-23 Impact factor: 44.544
Authors: Robert W Haile; Esther M John; A Joan Levine; Victoria K Cortessis; Jennifer B Unger; Melissa Gonzales; Elad Ziv; Patricia Thompson; Donna Spruijt-Metz; Katherine L Tucker; Jonine L Bernstein; Thomas E Rohan; Gloria Y F Ho; Melissa L Bondy; Maria Elena Martinez; Linda Cook; Mariana C Stern; Marcia Cruz Correa; Jonelle Wright; Seth J Schwartz; Lourdes Baezconde-Garbanati; Victoria Blinder; Patricia Miranda; Richard Hayes; George Friedman-Jiménez; Kristine R Monroe; Christopher A Haiman; Brian E Henderson; Duncan C Thomas; Paolo Boffetta Journal: Cancer Prev Res (Phila) Date: 2012-02
Authors: Allison W Kurian; Kevin C Ward; Nadia Howlader; Dennis Deapen; Ann S Hamilton; Angela Mariotto; Daniel Miller; Lynne S Penberthy; Steven J Katz Journal: J Clin Oncol Date: 2019-04-09 Impact factor: 44.544
Authors: Anne Marie McCarthy; Mirar Bristol; Susan M Domchek; Peter W Groeneveld; Younji Kim; U Nkiru Motanya; Judy A Shea; Katrina Armstrong Journal: J Clin Oncol Date: 2016-05-09 Impact factor: 44.544
Authors: Anita Y Kinney; Rachel Howell; Rachel Ruckman; Jean A McDougall; Tawny W Boyce; Belinda Vicuña; Ji-Hyun Lee; Dolores D Guest; Randi Rycroft; Patricia A Valverde; Kristina M Gallegos; Angela Meisner; Charles L Wiggins; Antoinette Stroup; Lisa E Paddock; Scott T Walters Journal: Contemp Clin Trials Date: 2018-09-18 Impact factor: 2.226
Authors: Deborah Cragun; Anne Weidner; Courtney Lewis; Devon Bonner; Jongphil Kim; Susan T Vadaparampil; Tuya Pal Journal: Cancer Date: 2017-02-09 Impact factor: 6.860
Authors: Tuya Pal; Devon Bonner; Deborah Cragun; Alvaro N A Monteiro; Catherine Phelan; Lily Servais; Jongphil Kim; Steven A Narod; Mohammad R Akbari; Susan T Vadaparampil Journal: Cancer Date: 2015-08-19 Impact factor: 6.860