PURPOSE: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. METHODS: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. RESULTS: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. CONCLUSION: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.
PURPOSE: Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. METHODS: Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. RESULTS: Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. CONCLUSION: Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care.
Authors: Steven A Narod; Marie-Pierre Dubé; Jan Klijn; Jan Lubinski; Henry T Lynch; Parviz Ghadirian; Diane Provencher; Ketil Heimdal; Pal Moller; Mark Robson; Kenneth Offit; Claudine Isaacs; Barbara Weber; Eitan Friedman; Ruth Gershoni-Baruch; Gad Rennert; Barbara Pasini; Theresa Wagner; Mary Daly; Judy E Garber; Susan L Neuhausen; Peter Ainsworth; Hakan Olsson; Gareth Evans; Michael Osborne; Fergus Couch; William D Foulkes; Ellen Warner; Charmaine Kim-Sing; Olufunmilayo Olopade; Nadine Tung; Howard M Saal; Jeffrey Weitzel; Sofia Merajver; Marion Gauthier-Villars; Helena Jernstrom; Ping Sun; Jean-Sebastien Brunet Journal: J Natl Cancer Inst Date: 2002-12-04 Impact factor: 13.506
Authors: Susan M Domchek; Tara M Friebel; Christian F Singer; D Gareth Evans; Henry T Lynch; Claudine Isaacs; Judy E Garber; Susan L Neuhausen; Ellen Matloff; Rosalind Eeles; Gabriella Pichert; Laura Van t'veer; Nadine Tung; Jeffrey N Weitzel; Fergus J Couch; Wendy S Rubinstein; Patricia A Ganz; Mary B Daly; Olufunmilayo I Olopade; Gail Tomlinson; Joellen Schildkraut; Joanne L Blum; Timothy R Rebbeck Journal: JAMA Date: 2010-09-01 Impact factor: 56.272
Authors: D Ford; D F Easton; M Stratton; S Narod; D Goldgar; P Devilee; D T Bishop; B Weber; G Lenoir; J Chang-Claude; H Sobol; M D Teare; J Struewing; A Arason; S Scherneck; J Peto; T R Rebbeck; P Tonin; S Neuhausen; R Barkardottir; J Eyfjord; H Lynch; B A Ponder; S A Gayther; M Zelada-Hedman Journal: Am J Hum Genet Date: 1998-03 Impact factor: 11.025
Authors: S A Gayther; J Mangion; P Russell; S Seal; R Barfoot; B A Ponder; M R Stratton; D Easton Journal: Nat Genet Date: 1997-01 Impact factor: 38.330
Authors: Susan M Domchek; Tara M Friebel; Susan L Neuhausen; Theresa Wagner; Gareth Evans; Claudine Isaacs; Judy E Garber; Mary B Daly; Rosalind Eeles; Ellen Matloff; Gail E Tomlinson; Laura Van't Veer; Henry T Lynch; Olufunmilayo I Olopade; Barbara L Weber; Timothy R Rebbeck Journal: Lancet Oncol Date: 2006-03 Impact factor: 41.316
Authors: Jenny Chang-Claude; Nadine Andrieu; Matti Rookus; Richard Brohet; Antonis C Antoniou; Susan Peock; Rosemarie Davidson; Louise Izatt; Trevor Cole; Catherine Noguès; Elisabeth Luporsi; Laetitia Huiart; Nicoline Hoogerbrugge; Flora E Van Leeuwen; Ana Osorio; Jorunn Eyfjord; Paolo Radice; David E Goldgar; Douglas F Easton Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-04 Impact factor: 4.254
Authors: Stephanie L Wethington; Kay J Park; Robert A Soslow; Noah D Kauff; Carol L Brown; Fanny Dao; Ebunoluwa Otegbeye; Yukio Sonoda; Nadeem R Abu-Rustum; Richard R Barakat; Douglas A Levine; Ginger J Gardner Journal: Int J Gynecol Cancer Date: 2013-11 Impact factor: 3.437
Authors: Mikaela D Stewart; Elena Zelin; Abhinav Dhall; Tom Walsh; Esha Upadhyay; Jacob E Corn; Champak Chatterjee; Mary-Claire King; Rachel E Klevit Journal: Proc Natl Acad Sci U S A Date: 2018-01-24 Impact factor: 11.205
Authors: Dana Madorsky-Feldman; Miri Sklair-Levy; Tamar Perri; Yael Laitman; Shani Paluch-Shimon; Rita Schmutzler; Kerstin Rhiem; Jenny Lester; Beth Y Karlan; Christian F Singer; Tom Van Maerken; Kathleen Claes; Joan Brunet; Angel Izquierdo; Alex Teulé; Jong Won Lee; Sung-Won Kim; Banu Arun; Anna Jakubowska; Jan Lubinski; Katherine Tucker; Nicola K Poplawski; Liliana Varesco; Luigina Ada Bonelli; Saundra S Buys; Gillian Mitchell; Marc Tischkowitz; Anne-Marie Gerdes; Caroline Seynaeve; Mark Robson; Ava Kwong; Nadine Tung; Nalven Tessa; Susan M Domchek; Andrew K Godwin; Johanna Rantala; Brita Arver; Eitan Friedman Journal: Breast Cancer Res Treat Date: 2016-04-27 Impact factor: 4.872
Authors: George U Eleje; Ahizechukwu C Eke; Ifeanyichukwu U Ezebialu; Joseph I Ikechebelu; Emmanuel O Ugwu; Onyinye O Okonkwo Journal: Cochrane Database Syst Rev Date: 2018-08-24
Authors: Felipe C Silva; Bianca Cg Lisboa; Marcia Cp Figueiredo; Giovana T Torrezan; Erika Mm Santos; Ana C Krepischi; Benedito M Rossi; Maria I Achatz; Dirce M Carraro Journal: BMC Med Genet Date: 2014-05-15 Impact factor: 2.103