Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 24 (1), 308-16

Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Paolo Peterlongo  1 Jenny Chang-Claude  2 Kirsten B Moysich  3 Anja Rudolph  2 Rita K Schmutzler  4 Jacques Simard  5 Penny Soucy  5 Rosalind A Eeles  6 Douglas F Easton  7 Ute Hamann  8 Stefan Wilkening  9 Bowang Chen  10 Matti A Rookus  11 Marjanka K Schmidt  12 Frederieke H van der Baan  11 Amanda B Spurdle  13 Logan C Walker  14 Felicity Lose  13 Ana-Teresa Maia  15 Marco Montagna  16 Laura Matricardi  16 Jan Lubinski  17 Anna Jakubowska  17 Encarna B Gómez Garcia  18 Olufunmilayo I Olopade  19 Robert L Nussbaum  20 Katherine L Nathanson  21 Susan M Domchek  21 Timothy R Rebbeck  22 Banu K Arun  23 Beth Y Karlan  24 Sandra Orsulic  24 Jenny Lester  24 Wendy K Chung  25 Alex Miron  26 Melissa C Southey  27 David E Goldgar  28 Saundra S Buys  29 Ramunas Janavicius  30 Cecilia M Dorfling  31 Elizabeth J van Rensburg  31 Yuan Chun Ding  32 Susan L Neuhausen  32 Thomas V O Hansen  33 Anne-Marie Gerdes  34 Bent Ejlertsen  35 Lars Jønson  33 Ana Osorio  36 Cristina Martínez-Bouzas  37 Javier Benitez  38 Edye E Conway  39 Kathleen R Blazer  40 Jeffrey N Weitzel  41 Siranoush Manoukian  42 Bernard Peissel  42 Daniela Zaffaroni  42 Giulietta Scuvera  42 Monica Barile  43 Filomena Ficarazzi  44 Frederique Mariette  44 Stefano Fortuzzi  44 Alessandra Viel  45 Giuseppe Giannini  46 Laura Papi  47 Aline Martayan  48 Maria Grazia Tibiletti  49 Paolo Radice  50 Athanassios Vratimos  51 Florentia Fostira  51 Judy E Garber  52 Alan Donaldson  53 Carole Brewer  54 Claire Foo  55 D Gareth R Evans  56 Debra Frost  7 Diana Eccles  57 Angela Brady  58 Jackie Cook  59 Marc Tischkowitz  60 Julian Adlard  61 Julian Barwell  62 Lisa Walker  63 Louise Izatt  64 Lucy E Side  65 M John Kennedy  66 Mark T Rogers  67 Mary E Porteous  68 Patrick J Morrison  69 Radka Platte  7 Rosemarie Davidson  70 Shirley V Hodgson  71 Steve Ellis  7 Trevor Cole  72 EMBRACEAndrew K Godwin  73 Kathleen Claes  74 Tom Van Maerken  74 Alfons Meindl  75 Andrea Gehrig  76 Christian Sutter  77 Christoph Engel  78 Dieter Niederacher  79 Doris Steinemann  80 Hansjoerg Plendl  81 Karin Kast  82 Kerstin Rhiem  83 Nina Ditsch  84 Norbert Arnold  85 Raymonda Varon-Mateeva  86 Barbara Wappenschmidt  83 Shan Wang-Gohrke  87 Brigitte Bressac-de Paillerets  88 Bruno Buecher  89 Capucine Delnatte  90 Claude Houdayer  91 Dominique Stoppa-Lyonnet  92 Francesca Damiola  93 Isabelle Coupier  94 Laure Barjhoux  95 Laurence Venat-Bouvet  96 Lisa Golmard  89 Nadia Boutry-Kryza  97 Olga M Sinilnikova  98 Olivier Caron  99 Pascal Pujol  100 Sylvie Mazoyer  93 Muriel Belotti  89 GEMO Study CollaboratorsMarion Piedmonte  101 Michael L Friedlander  102 Gustavo C Rodriguez  103 Larry J Copeland  104 Miguel de la Hoya  105 Pedro Perez Segura  106 Heli Nevanlinna  107 Kristiina Aittomäki  108 Theo A M van Os  109 Hanne E J Meijers-Heijboer  110 Annemarie H van der Hout  111 Maaike P G Vreeswijk  112 Nicoline Hoogerbrugge  113 Margreet G E M Ausems  114 Helena C van Doorn  115 J Margriet Collée  116 HEBONEdith Olah  117 Orland Diez  118 Ignacio Blanco  119 Conxi Lazaro  120 Joan Brunet  121 Lidia Feliubadalo  122 Cezary Cybulski  17 Jacek Gronwald  17 Katarzyna Durda  17 Katarzyna Jaworska-Bieniek  17 Grzegorz Sukiennicki  17 Adalgeir Arason  123 Jocelyne Chiquette  124 Manuel R Teixeira  125 Curtis Olswold  126 Fergus J Couch  127 Noralane M Lindor  128 Xianshu Wang  129 Csilla I Szabo  130 Kenneth Offit  131 Marina Corines  132 Lauren Jacobs  132 Mark E Robson  131 Liying Zhang  133 Vijai Joseph  131 Andreas Berger  134 Christian F Singer  134 Christine Rappaport  134 Daphne Geschwantler Kaulich  134 Georg Pfeiler  134 Muy-Kheng M Tea  134 Catherine M Phelan  135 Mark H Greene  136 Phuong L Mai  136 Gad Rennert  137 Anna Marie Mulligan  138 Gord Glendon  139 Sandrine Tchatchou  140 Irene L Andrulis  141 Amanda Ewart Toland  142 Anders Bojesen  143 Inge Sokilde Pedersen  144 Mads Thomassen  145 Uffe Birk Jensen  146 Yael Laitman  147 Johanna Rantala  148 Anna von Wachenfeldt  149 Hans Ehrencrona  150 Marie Stenmark Askmalm  151 Åke Borg  152 Karoline B Kuchenbaecker  7 Lesley McGuffog  7 Daniel Barrowdale  7 Sue Healey  13 Andrew Lee  7 Paul D P Pharoah  153 Georgia Chenevix-Trench  13 KConFab InvestigatorsAntonis C Antoniou  7 Eitan Friedman  154
Affiliations

Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Paolo Peterlongo et al. Cancer Epidemiol Biomarkers Prev.

Abstract

Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.

Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.

Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.

Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

Conflict of interest statement

Disclosure of potential conflict of interest: All authors declare that they have no conflicts of interest.

Similar articles

  • A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers.
    Ding YC, McGuffog L, Healey S, Friedman E, Laitman Y, Paluch-Shimon S, Kaufman B; SWE-BRCA, Liljegren A, Lindblom A, Olsson H, Kristoffersson U, Stenmark-Askmalm M, Melin B, Domchek SM, Nathanson KL, Rebbeck TR, Jakubowska A, Lubinski J, Jaworska K, Durda K, Gronwald J, Huzarski T, Cybulski C, Byrski T, Osorio A, Cajal TR, Stavropoulou AV, Benítez J, Hamann U; HEBON, Rookus M, Aalfs CM, de Lange JL, Meijers-Heijboer HE, Oosterwijk JC, van Asperen CJ, Gómez García EB, Hoogerbrugge N, Jager A, van der Luijt RB; EMBRACE, Easton DF, Peock S, Frost D, Ellis SD, Platte R, Fineberg E, Evans DG, Lalloo F, Izatt L, Eeles R, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Tischkowitz M, Godwin AK, Pathak H; GEMO Study Collaborators, Stoppa-Lyonnet D, Sinilnikova OM, Mazoyer S, Barjhoux L, Léoné M, Gauthier-Villars M, Caux-Moncoutier V, de Pauw A, Hardouin A, Berthet P, Dreyfus H, Ferrer SF, Collonge-Rame MA, Sokolowska J, Buys S, Daly M, Miron A, Terry MB, Chung W, John EM, Southey M, Goldgar D, Singer CF, Tea MK, Gschwantler-Kaulich D, Fink-Retter A, Hansen TV, Ejlertsen B, Johannsson OT, Offit K, Sarrel K, Gaudet MM, Vijai J, Robson M, Piedmonte MR, Andrews L, Cohn D, DeMars LR, DiSilvestro P, Rodriguez G, Toland AE, Montagna M, Agata S, Imyanitov E, Isaacs C, Janavicius R, Lazaro C, Blanco I, Ramus SJ, Sucheston L, Karlan BY, Gross J, Ganz PA, Beattie MS, Schmutzler RK, Wappenschmidt B, Meindl A, Arnold N, Niederacher D, Preisler-Adams S, Gadzicki D, Varon-Mateeva R, Deissler H, Gehrig A, Sutter C, Kast K, Nevanlinna H, Aittomäki K, Simard J; KConFab Investigators, Spurdle AB, Beesley J, Chen X, Tomlinson GE, Weitzel J, Garber JE, Olopade OI, Rubinstein WS, Tung N, Blum JL, Narod SA, Brummel S, Gillen DL, Lindor N, Fredericksen Z, Pankratz VS, Couch FJ, Radice P, Peterlongo P, Greene MH, Loud JT, Mai PL, Andrulis IL, Glendon G, Ozcelik H; OCGN, Gerdes AM, Thomassen M, Jensen UB, Skytte AB, Caligo MA, Lee A, Chenevix-Trench G, Antoniou AC, Neuhausen SL; Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Ding YC, et al. Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1362-70. doi: 10.1158/1055-9965.EPI-12-0229. Epub 2012 Jun 22. Cancer Epidemiol Biomarkers Prev. 2012. PMID: 22729394 Free PMC article. Clinical Trial.
  • The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers.
    Jakubowska A, Rozkrut D, Antoniou A, Hamann U, Lubinski J. Jakubowska A, et al. Breast Cancer Res Treat. 2010 Jun;121(3):639-49. doi: 10.1007/s10549-009-0595-7. Epub 2009 Oct 30. Breast Cancer Res Treat. 2010. PMID: 19876733 Free PMC article. Clinical Trial.
  • Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.
    Ramus SJ, Kartsonaki C, Gayther SA, Pharoah PD, Sinilnikova OM, Beesley J, Chen X, McGuffog L, Healey S, Couch FJ, Wang X, Fredericksen Z, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Roversi G, Barile M, Viel A, Allavena A, Ottini L, Papi L, Gismondi V, Capra F, Radice P, Greene MH, Mai PL, Andrulis IL, Glendon G, Ozcelik H; OCGN, Thomassen M, Gerdes AM, Kruse TA, Cruger D, Jensen UB, Caligo MA, Olsson H, Kristoffersson U, Lindblom A, Arver B, Karlsson P, Stenmark Askmalm M, Borg A, Neuhausen SL, Ding YC, Nathanson KL, Domchek SM, Jakubowska A, Lubiński J, Huzarski T, Byrski T, Gronwald J, Górski B, Cybulski C, Dębniak T, Osorio A, Durán M, Tejada MI, Benítez J, Hamann U, Rookus MA, Verhoef S, Tilanus-Linthorst MA, Vreeswijk MP, Bodmer D, Ausems MG, van Os TA, Asperen CJ, Blok MJ, Meijers-Heijboer HE; HEBON; EMBRACE, Peock S, Cook M, Oliver C, Frost D, Dunning AM, Evans DG, Eeles R, Pichert G, Cole T, Hodgson S, Brewer C, Morrison PJ, Porteous M, Kennedy MJ, Rogers MT, Side LE, Donaldson A, Gregory H, Godwin A, Stoppa-Lyonnet D, Moncoutier V, Castera L, Mazoyer S, Barjhoux L, Bonadona V, Leroux D, Faivre L, Lidereau R, Nogues C, Bignon YJ, Prieur F, Collonge-Rame MA, Venat-Bouvet L, Fert-Ferrer S; GEMO Study Collaborators, Miron A, Buys SS, Hopper JL, Daly MB, John EM, Terry MB, Goldgar D; BCFR, Hansen Tv, Jønson L, Ejlertsen B, Agnarsson BA, Offit K, Kirchhoff T, Vijai J, Dutra-Clarke AV, Przybylo JA, Montagna M, Casella C, Imyanitov EN, Janavicius R, Blanco I, Lázaro C, Moysich KB, Karlan BY, Gross J, Beattie MS, Schmutzler R, Wappenschmidt B, Meindl A, Ruehl I, Fiebig B, Sutter C, Arnold N, Deissler H, Varon-Mateeva R, Kast K, Niederacher D, Gadzicki D, Caldes T, de la Hoya M, Nevanlinna H, Aittomäki K, Simard J, Soucy P; kConFab Investigators, Spurdle AB, Holland H, Chenevix-Trench G, Easton DF, Antoniou AC; Consortium of Investigators of Modifiers of BRCA1/2. Ramus SJ, et al. J Natl Cancer Inst. 2011 Jan 19;103(2):105-16. doi: 10.1093/jnci/djq494. Epub 2010 Dec 17. J Natl Cancer Inst. 2011. PMID: 21169536 Free PMC article.
  • Genetic modifiers of cancer risk for BRCA1 and BRCA2 mutation carriers.
    Milne RL, Antoniou AC. Milne RL, et al. Ann Oncol. 2011 Jan;22 Suppl 1:i11-7. doi: 10.1093/annonc/mdq660. Ann Oncol. 2011. PMID: 21285145 Review.
  • [Hereditary breast and ovarian cancer: primary and secondary prevention for BRCA1 and BRCA2 mutation carriers].
    Llort G, Peris M, Blanco I. Llort G, et al. Med Clin (Barc). 2007 Mar 31;128(12):468-76. doi: 10.1157/13100569. Med Clin (Barc). 2007. PMID: 17408542 Review. Spanish.
See all similar articles

Cited by 10 articles

See all "Cited by" articles

Publication types

Grant support

Feedback