Biopolym. Cell. 2017; 33(5):393-400.
Біомедицина
Визначення асоціації носійства генетичних поліморфізмів з мутаційним статусом генів BRCA1/2 при спонтанному раку молочної залози
1Поліник С. І., 1Рибченко Л. А., 1Клименко С. В., 2Захарцева Л. М., 3Клімук Б. Т.
  1. Державна установа "Національний науковий центр радіаційної медицини НАМН України
    вул. Мельникова 53, Київ, Україна, 04050
  2. Національний медичний університет імені О. О. Богомольця
    13, бульв. Тараса Шевченка, Київ, Україна, 01601
  3. Національний технічний університет України "Київський політехнічний інститут імені Ігоря Сікорського"
    пр-т Перемоги, 37, Київ, Україна, 03056

Abstract

Мета. Визначення асоціації носійства генетичних поліморфізмів генів FGFR2, TOX3/LOC643714 з мутаційним статусом генів BRCA1/2 у жінок України хворих на рак молочної залози, які не мають впливу іонізуючого випромінювання в анамнезі. Методи. Молекулярно-генетичні методи дослідження. Непараметричні дані оцінювали з використанням точного тесту Фішера в двобічному варіанті. Статистичний аналіз проводили з використанням пакету програми StatPlus Pro. Результати. Показано,що існують асоціації носійства генетичних поліморфізмів rs2981582 гена FGFR2, rs3803662 гена TOX3/LOC643714 з мутаційним статусом генів BRCA1/2 жінок хворих на РМЗ без іонізуючого випромінювання в анамнезі. Висновки. Серед досліджених генетичних поліморфізмів достовірним виявили асоціацію між мінорним генотипом ТТгена TOX3/LOC643714 та позитивним статусом гена BRCA1. Не знайдено статистичної асоціації серед гомозигот за мажорними алелями та гетерозигот поліморфізмів генів FGFR2, TOX3/LOC643714, з наявністю або відсутністю мутацій BRCA1/2 (p < 0,05).
Keywords: рак молочної залози, генетичні поліморфізми, мутації BRCA1/2

References

[1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917. doi:
[2] Rak v Ukrayini, 2007-2008. Pid red. IB Shhepotina. Byuleten nacionalnogo kancer-reyestru Ukrayiny. 2009. N 10.
[3] Foulkes WD. Inherited susceptibility to common cancers. N Engl J Med. 2008;359(20):2143-53. doi:
[4] Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117-30. Erratum in: Am J Hum Genet. 2003 Sep;73(3):709.
[5] Metcalfe K, Lubinski J, Lynch HT, Ghadirian P, Foulkes WD, Kim-Sing C, Neuhausen S, Tung N, Rosen B, Gronwald J, Ainsworth P, Sweet K, Eisen A, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. Family history of cancer and cancer risks in women with BRCA1 or BRCA2 mutations. J Natl Cancer Inst. 2010;102(24):1874-8. doi:
[6] Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia. 2004;9(3):221-36.
[7] Antoniou AC, Easton DF. Models of genetic susceptibility to breast cancer. Oncogene. 2006;25(43):5898-905.
[8] Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R; SEARCH collaborators, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schürmann P, Dörk T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X; kConFab; AOCS Management Group, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BA. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447(7148):1087-93.
[9] Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BA. Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet. 2002;31(1):33-6.
[10] Dai J, Hu Z, Jiang Y, Shen H, Dong J, Ma H, Shen H. Breast cancer risk assessment with five independent genetic variants and two risk factors in Chinese women. Breast Cancer Res. 2012;14(1):R17.
[11] Harlid S, Ivarsson MI, Butt S, Grzybowska E, Eyfjörd JE, Lenner P, Försti A, Hemminki K, Manjer J, Dillner J, Carlson J. Combined effect of low-penetrant SNPs on breast cancer risk. Br J Cancer. 2012;106(2):389-96. doi:
[12] MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, Junkins H, McMahon A, Milano A, Morales J, Pendlington ZM, Welter D, Burdett T, Hindorff L, Flicek P, Cunningham F, Parkinson H. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 2017;45(D1):D896-D901. doi:
[13] Antoniou AC, Pharoah PD, McMullan G, Day NE, Stratton MR, Peto J, Ponder BJ, Easton DF. A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes. Br J Cancer. 2002;86(1):76-83.
[14] Wang WY, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet. 2005;6(2):109-18.
[15] Barnholtz-Sloan JS, Shetty PB, Guan X, Nyante SJ, Luo J, Brennan DJ, Millikan RC. FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women. Carcinogenesis. 2010;31(8):1417-23. doi:
[16] Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, Seal S, Ghoussaini M, Hines S, Healey CS, Hughes D, Warren-Perry M, Tapper W, Eccles D, Evans DG; Breast Cancer Susceptibility Collaboration (UK), Hooning M, Schutte M, van den Ouweland A, Houlston R, Ross G, Langford C, Pharoah PD, Stratton MR, Dunning AM, Rahman N, Easton DF. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet. 2010;42(6):504-7. doi:
[17] Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Thomas G, Chanock SJ. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007;39(7):870-4.
[18] Antoniou AC, Pharoah PP, Smith P, Easton DF. The BOADICEA model of genetic susceptibility to breast and ovarian cancer. Br J Cancer. 2004;91(8):1580-90.
[19] Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol. 2010;4(3):174-91. doi:
[20] Antoniou AC, Sinilnikova OM, McGuffog L, Healey S, Nevanlinna H, Heikkinen T, Simard J, Spurdle AB, Beesley J, Chen X; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Neuhausen SL, Ding YC, Couch FJ, Wang X, Fredericksen Z, Peterlongo P, Peissel B, Bonanni B, Viel A, Bernard L, Radice P, Szabo CI, Foretova L, Zikan M, Claes K, Greene MH, Mai PL, Rennert G, Lejbkowicz F, Andrulis IL, Ozcelik H, Glendon G; OCGN, Gerdes AM, Thomassen M, Sunde L, Caligo MA, Laitman Y, Kontorovich T, Cohen S, Kaufman B, Dagan E, Baruch RG, Friedman E, Harbst K, Barbany-Bustinza G, Rantala J, Ehrencrona H, Karlsson P, Domchek SM, Nathanson KL, Osorio A, Blanco I, Lasa A, Benítez J, Hamann U, Hogervorst FB, Rookus MA, Collee JM, Devilee P, Ligtenberg MJ, van der Luijt RB, Aalfs CM, Waisfisz Q, Wijnen J, van Roozendaal CE; HEBON, Peock S, Cook M, Frost D, Oliver C, Platte R, Evans DG, Lalloo F, Eeles R, Izatt L, Davidson R, Chu C, Eccles D, Cole T, Hodgson S; EMBRACE, Godwin AK, Stoppa-Lyonnet D, Buecher B, Léoné M, Bressac-de Paillerets B, Remenieras A, Caron O, Lenoir GM, Sevenet N, Longy M, Ferrer SF, Prieur F; GEMO, Goldgar D, Miron A, John EM, Buys SS, Daly MB, Hopper JL, Terry MB, Yassin Y; Breast Cancer Family Registry, Singer C, Gschwantler-Kaulich D, Staudigl C, Hansen Tv, Barkardottir RB, Kirchhoff T, Pal P, Kosarin K, Offit K, Piedmonte M, Rodriguez GC, Wakeley K, Boggess JF, Basil J, Schwartz PE, Blank SV, Toland AE, Montagna M, Casella C, Imyanitov EN, Allavena A, Schmutzler RK, Versmold B, Engel C, Meindl A, Ditsch N, Arnold N, Niederacher D, Deissler H, Fiebig B, Suttner C, Schönbuchner I, Gadzicki D, Caldes T, de la Hoya M, Pooley KA, Easton DF, Chenevix-Trench G; CIMBA. Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers. Hum Mol Genet. 2009;18(22):4442-56. doi:
[21] Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Hofmann W, Sutter C, Niederacher D, Deissler H, Caldes T, Kämpjärvi K, Nevanlinna H, Simard J, Beesley J, Chen X; Kathleen Cuningham Consortium for Research into Familial Breast Cancer, Neuhausen SL, Rebbeck TR, Wagner T, Lynch HT, Isaacs C, Weitzel J, Ganz PA, Daly MB, Tomlinson G, Olopade OI, Blum JL, Couch FJ, Peterlongo P, Manoukian S, Barile M, Radice P, Szabo CI, Pereira LH, Greene MH, Rennert G, Lejbkowicz F, Barnett-Griness O, Andrulis IL, Ozcelik H; OCGN, Gerdes AM, Caligo MA, Laitman Y, Kaufman B, Milgrom R, Friedman E; Swedish BRCA1 and BRCA2 study collaborators, Domchek SM, Nathanson KL, Osorio A, Llort G, Milne RL, Benítez J, Hamann U, Hogervorst FB, Manders P, Ligtenberg MJ, van den Ouweland AM; DNA-HEBON collaborators, Peock S, Cook M, Platte R, Evans DG, Eeles R, Pichert G, Chu C, Eccles D, Davidson R, Douglas F; EMBRACE, Godwin AK, Barjhoux L, Mazoyer S, Sobol H, Bourdon V, Eisinger F, Chompret A, Capoulade C, Bressac-de Paillerets B, Lenoir GM, Gauthier-Villars M, Houdayer C, Stoppa-Lyonnet D; GEMO, Chenevix-Trench G, Easton DF; CIMBA. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet. 2008;82(4):937-48.
[22] Garcia-Closas M, Hall P, Nevanlinna H, Pooley K, Morrison J, Richesson DA, Bojesen SE, Nordestgaard BG, Axelsson CK, Arias JI, Milne RL, Ribas G, González-Neira A, Benítez J, Zamora P, Brauch H, Justenhoven C, Hamann U, Ko YD, Bruening T, Haas S, Dörk T, Schürmann P, Hillemanns P, Bogdanova N, Bremer M, Karstens JH, Fagerholm R, Aaltonen K, Aittomäki K, von Smitten K, Blomqvist C, Mannermaa A, Uusitupa M, Eskelinen M, Tengström M, Kosma VM, Kataja V, Chenevix-Trench G, Spurdle AB, Beesley J, Chen X; Australian Ovarian Cancer Management Group; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Devilee P, van Asperen CJ, Jacobi CE, Tollenaar RA, Huijts PE, Klijn JG, Chang-Claude J, Kropp S, Slanger T, Flesch-Janys D, Mutschelknauss E, Salazar R, Wang-Gohrke S, Couch F, Goode EL, Olson JE, Vachon C, Fredericksen ZS, Giles GG, Baglietto L, Severi G, Hopper JL, English DR, Southey MC, Haiman CA, Henderson BE, Kolonel LN, Le Marchand L, Stram DO, Hunter DJ, Hankinson SE, Cox DG, Tamimi R, Kraft P, Sherman ME, Chanock SJ, Lissowska J, Brinton LA, Peplonska B, Klijn JG, Hooning MJ, Meijers-Heijboer H, Collee JM, van den Ouweland A, Uitterlinden AG, Liu J, Lin LY, Yuqing L, Humphreys K, Czene K, Cox A, Balasubramanian SP, Cross SS, Reed MW, Blows F, Driver K, Dunning A, Tyrer J, Ponder BA, Sangrajrang S, Brennan P, McKay J, Odefrey F, Gabrieau V, Sigurdson A, Doody M, Struewing JP, Alexander B, Easton DF, Pharoah PD. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008;4(4):e1000054. doi:
[23] Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ, Albers-Akkers MT, Swinkels DW, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Godino J, Garcia-Prats MD, Polo E, Tres A, Mouy M, Saemundsdottir J, Backman VM, Gudmundsson L, Kristjansson K, Bergthorsson JT, Kostic J, Frigge ML, Geller F, Gudbjartsson D, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Jonsson T, von Holst S, Werelius B, Margolin S, Lindblom A, Mayordomo JI, Haiman CA, Kiemeney LA, Johannsson OT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet. 2007;39(7):865-9.
[24] Peng S, Lü B, Ruan W, Zhu Y, Sheng H, Lai M. Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies. Breast Cancer Res Treat. 2011;127(2):309-24. doi:
[25] Baynes C, Healey CS, Pooley KA, Scollen S, Luben RN, Thompson DJ, Pharoah PD, Easton DF, Ponder BA, Dunning AM; SEARCH breast cancer study. Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast Cancer Res. 2007;9(2):R27.
[26] Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL, Ding YC, Rebbeck TR, Weitzel JN, Lynch HT, Isaacs C, Ganz PA, Tomlinson G, Olopade OI, Couch FJ, Wang X, Lindor NM, Pankratz VS, Radice P, Manoukian S, Peissel B, Zaffaroni D, Barile M, Viel A, Allavena A, Dall'Olio V, Peterlongo P, Szabo CI, Zikan M, Claes K, Poppe B, Foretova L, Mai PL, Greene MH, Rennert G, Lejbkowicz F, Glendon G, Ozcelik H, Andrulis IL; Ontario Cancer Genetics Network, Thomassen M, Gerdes AM, Sunde L, Cruger D, Birk Jensen U, Caligo M, Friedman E, Kaufman B, Laitman Y, Milgrom R, Dubrovsky M, Cohen S, Borg A, Jernström H, Lindblom A, Rantala J, Stenmark-Askmalm M, Melin B; SWE-BRCA, Nathanson K, Domchek S, Jakubowska A, Lubinski J, Huzarski T, Osorio A, Lasa A, Durán M, Tejada MI, Godino J, Benitez J, Hamann U, Kriege M, Hoogerbrugge N, van der Luijt RB, van Asperen CJ, Devilee P, Meijers-Heijboer EJ, Blok MJ, Aalfs CM, Hogervorst F, Rookus M; HEBON, Cook M, Oliver C, Frost D, Conroy D, Evans DG, Lalloo F, Pichert G, Davidson R, Cole T, Cook J, Paterson J, Hodgson S, Morrison PJ, Porteous ME, Walker L, Kennedy MJ, Dorkins H, Peock S; EMBRACE, Godwin AK, Stoppa-Lyonnet D, de Pauw A, Mazoyer S, Bonadona V, Lasset C, Dreyfus H, Leroux D, Hardouin A, Berthet P, Faivre L; GEMO, Loustalot C, Noguchi T, Sobol H, Rouleau E, Nogues C, Frénay M, Vénat-Bouvet L; GEMO, Hopper JL, Daly MB, Terry MB, John EM, Buys SS, Yassin Y, Miron A, Goldgar D; Breast Cancer Family Registry, Singer CF, Dressler AC, Gschwantler-Kaulich D, Pfeiler G, Hansen TV, Jønson L, Agnarsson BA, Kirchhoff T, Offit K, Devlin V, Dutra-Clarke A, Piedmonte M, Rodriguez GC, Wakeley K, Boggess JF, Basil J, Schwartz PE, Blank SV, Toland AE, Montagna M, Casella C, Imyanitov E, Tihomirova L, Blanco I, Lazaro C, Ramus SJ, Sucheston L, Karlan BY, Gross J, Schmutzler R, Wappenschmidt B, Engel C, Meindl A, Lochmann M, Arnold N, Heidemann S, Varon-Mateeva R, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Kast K, Schönbuchner I, Caldes T, de la Hoya M, Aittomäki K, Nevanlinna H, Simard J, Spurdle AB, Holland H, Chen X; kConFab, Platte R, Chenevix-Trench G, Easton DF; CIMBA. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: impl
[27] Mulligan AM, Couch FJ, Barrowdale D, Domchek SM, Eccles D, Nevanlinna H, Ramus SJ, Robson M, Sherman M, Spurdle AB, Wappenschmidt B, Lee A, McGuffog L, Healey S, Sinilnikova OM, Janavicius R, Hansen Tv, Nielsen FC, Ejlertsen B, Osorio A, Muñoz-Repeto I, Durán M, Godino J, Pertesi M, Benítez J, Peterlongo P, Manoukian S, Peissel B, Zaffaroni D, Cattaneo E, Bonanni B, Viel A, Pasini B, Papi L, Ottini L, Savarese A, Bernard L, Radice P, Hamann U, Verheus M, Meijers-Heijboer HE, Wijnen J, Gómez García EB, Nelen MR, Kets CM, Seynaeve C, Tilanus-Linthorst MM, van der Luijt RB, van Os T, Rookus M, Frost D, Jones JL, Evans DG, Lalloo F, Eeles R, Izatt L, Adlard J, Davidson R, Cook J, Donaldson A, Dorkins H, Gregory H, Eason J, Houghton C, Barwell J, Side LE, McCann E, Murray A, Peock S, Godwin AK, Schmutzler RK, Rhiem K, Engel C, Meindl A, Ruehl I, Arnold N, Niederacher D, Sutter C, Deissler H, Gadzicki D, Kast K, Preisler-Adams S, Varon-Mateeva R, Schoenbuchner I, Fiebig B, Heinritz W, Schäfer D, Gevensleben H, Caux-Moncoutier V, Fassy-Colcombet M, Cornelis F, Mazoyer S, Léoné M, Boutry-Kryza N, Hardouin A, Berthet P, Muller D, Fricker JP, Mortemousque I, Pujol P, Coupier I, Lebrun M, Kientz C, Longy M, Sevenet N, Stoppa-Lyonnet D, Isaacs C, Caldes T, de la Hoya M, Heikkinen T, Aittomäki K, Blanco I, Lazaro C, Barkardottir RB, Soucy P, Dumont M, Simard J, Montagna M, Tognazzo S, D'Andrea E, Fox S, Yan M, Rebbeck T, Olopade O, Weitzel JN, Lynch HT, Ganz PA, Tomlinson GE, Wang X, Fredericksen Z, Pankratz VS, Lindor NM, Szabo C, Offit K, Sakr R, Gaudet M, Bhatia J, Kauff N, Singer CF, Tea MK, Gschwantler-Kaulich D, Fink-Retter A, Mai PL, Greene MH, Imyanitov E, O'Malley FP, Ozcelik H, Glendon G, Toland AE, Gerdes AM, Thomassen M, Kruse TA, Jensen UB, Skytte AB, Caligo MA, Soller M, Henriksson K, Wachenfeldt vA, Arver B, Stenmark-Askmalm M, Karlsson P, Ding YC, Neuhausen SL, Beattie M, Pharoah PD, Moysich KB, Nathanson KL, Karlan BY, Gross J, John EM, Daly MB, Buys SM, Southey MC, Hopper JL, Terry MB, Chung W, Miron AF, Goldgar D, Chenevix-Trench G, Easton DF, Andrulis IL, Antoniou AC; Breast Cancer Family Registry; EMBRACE; GEMO Study Collaborators; HEBON; kConFab Investigators; Ontario Cancer Genetics Network; SWE-BRCA; CIMBA. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Res. 2011;13(6):R110. doi:
[28] Latif A, Hadfield KD, Roberts SA, Shenton A, Lalloo F, Black GC, Howell A, Evans DG, Newman WG. Breast cancer susceptibility variants alter risks in familial disease. J Med Genet. 2010;47(2):126-31. doi:
[29] Elematore I, Gonzalez-Hormazabal P, Reyes JM, Blanco R, Bravo T, Peralta O, Gomez F, Waugh E, Margarit S, Ibañez G, Romero C, Pakomio J, Roizen G, Di Capua GA, Jara L. Association of genetic variants at TOX3, 2q35 and 8q24 with the risk of familial and early-onset breast cancer in a South-American population. Mol Biol Rep. 2014;41(6):3715-22. doi: