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1. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Author

Antoniou, AC, Kuchenbaecker, KB, Soucy, P, Beesley, J, Chen, X, McGuffog, L, Lee, A, Barrowdale, D, Healey, S, Sinilnikova, OM, Caligo, MA, Loman, N, Harbst, K, Lindblom, A, Arver, B, Rosenquist, R, Karlsson, P, Nathanson, K, Domchek, S, Rebbeck, T, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Zlowowcka-Perlowska, E, Osorio, A, Duran, M, Andres, R, Benitez, J, Hamann, U, Hogervorst, FB, van Os, TA, Verhoef, S, Meijers-Heijboer, HEJ, Wijnen, J, Garcia, EBG, Ligtenberg, MJ, Kriege, M, Collee, M, Ausems, MGEM, Oosterwijk, JC, Peock, S, Frost, D, Ellis, SD, Platte, R, Fineberg, E, Evans, DG, Lalloo, F, Jacobs, C, Eeles, R, Adlard, J, Davidson, R, Cole, T, Cook, J, Paterson, J, Douglas, F, Brewer, C, Hodgson, S, Morrison, PJ, Walker, L, Rogers, MT, Donaldson, A, Dorkins, H, Godwin, AK, Bove, B, Stoppa-Lyonnet, D, Houdayer, C, Buecher, B, de Pauw, A, Mazoyer, S, Calender, A, Leone, M, Bressac-de Paillerets, B, Caron, O, Sobol, H, Frenay, M, Prieur, F, Ferrer, SF, Mortemousque, I, Buys, S, Daly, M, Miron, A, Terry, MB, Hopper, JL, John, EM, Southey, M, Goldgar, D, Singer, CF, Fink-Retter, A, Tea, M-K, Kaulich, DG, Hansen, TVO, Nielsen, FC, Barkardottir, RB, Gaudet, M, Kirchhoff, T, Joseph, V, Dutra-Clarke, A, Offit, K, and Piedmonte, M

Published
2012

3. Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer: Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study)

Author

Terra, L., Hooning, M.J., Heemskerk-Gerritsen, B.A., Beurden, M. van, Lennep, J.E.Roeters van, Doorn, H.C. van, de Hullu, J.A., Mom, C., Dorst, E.B.L. van, Mourits, M.J.E., Slangen, B.F.M., Gaarenstroom, K.N., Zillikens, M.C., Leiner, T., Kolk, L. van der, Collee, M., Wevers, M.R., Ausems, M., Engelen, K. van, Berger, L.P.V., Asperen, C.J. van, Gomez-Garcia, E.B., Beek, I. van de, Rookus, Matti A., Hauptmann, M., Bleiker, E.M.A., Schagen, S.B., Aaronson, N.K., Maas, A.H.E.M., Leeuwen, F.E. van, Terra, L., Hooning, M.J., Heemskerk-Gerritsen, B.A., Beurden, M. van, Lennep, J.E.Roeters van, Doorn, H.C. van, de Hullu, J.A., Mom, C., Dorst, E.B.L. van, Mourits, M.J.E., Slangen, B.F.M., Gaarenstroom, K.N., Zillikens, M.C., Leiner, T., Kolk, L. van der, Collee, M., Wevers, M.R., Ausems, M., Engelen, K. van, Berger, L.P.V., Asperen, C.J. van, Gomez-Garcia, E.B., Beek, I. van de, Rookus, Matti A., Hauptmann, M., Bleiker, E.M.A., Schagen, S.B., Aaronson, N.K., Maas, A.H.E.M., and Leeuwen, F.E. van

Abstract

Contains fulltext : 232463.pdf (Publisher’s version ) (Open Access), BACKGROUND: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. OBJECTIVE: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. METHODS: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. RESULTS: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. CONCLUSIONS: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to o

Published
2021

4. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Author

Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., Schmutzler R.K., Ramus S.J., Carroll J.S., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Scott C., Scott R.J., Senter L., Shah M., Sharma P., Shen C.-Y., Shu X.-O., Singer C.F., Slavin T.P., Smichkoska S., Spinelli J.J., Spurdle A.B., Sutter C., Swerdlow A.J., Tamimi R.M., Tan Y.Y., Tapper W.J., Taylor J., Teixeira M.R., Tengstrom M., Teo S.H., Terry M.B., Teule A., Thomassen M., Thull D.L., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Torres-Mejia G., Troester M.A., Truong T., Tung N., Tzardi M., Ulmer H.-U., Vachon C.M., van der Kolk L.E., van Rensburg E.J., Vega A., Viel A., Vijai J., Vogel M.J., Wang Q., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wendt C., Wildiers H., Winqvist R., Wolk A., Wu A.H., Yannoukakos D., Zhang Y., Zheng W., Hunter D., Pharoah P.D.P., Chang-Claude J., Garcia-Closas M., Schmidt M.K., Kristensen V.N., French J.D., Antoniou A.C., Chenevix-Trench G., Simard J., Easton D.F., Kraft P., Allen J., Harris M., Fachal L., Aschard H., Beesley J., Barnes D.R., Kar S., Pooley K.A., Dennis J., Michailidou K., Turman C., Soucy P., Lemacon A., Lush M., Tyrer J.P., Ghoussaini M., Marjaneh M.M., Jiang X., Agata S., Aittomaki K., Alonso M.R., Andrulis I.L., Anton-Culver H., Antonenkova N.N., Arason A., Arndt V., Aronson K.J., Arun B.K., Auber B., Auer P.L., Azzollini J., Balmana J., Barkardottir R.B., Barrowdale D., Beeghly-Fadiel A., Benitez J., Bermisheva M., Bialkowska K., Blanco A.M., Blomqvist C., Blot W., Bogdanova N.V., Bojesen S.E., Bolla M.K., Bonanni B., Borg A., Bosse K., Brauch H., Brenner H., Briceno I., Brock I.W., Brooks-Wilson A., Bruning T., Burwinkel B., Buys S.S., Cai Q., Caldes T., Caligo M.A., Camp N.J., Campbell I., Carter B.D., Castelao J.E., Chiquette J., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Mari V., Berthet P., Castera L., Vaur D., Lallaoui H., Bignon Y.-J., Uhrhammer N., Bonadona V., Lasset C., Revillion F., Vennin P., Muller D., Gomes D.M., Ingster O., Coupier I., Pujol P., Collonge-Rame M.-A., Mortemousque I., Bera O., Rose M., Baurand A., Bertolone G., Faivre L., Dreyfus H., Leroux D., Venat-Bouvet L., Bezieau S., Delnatte C., Chiesa J., Gilbert-Dussardier B., Gesta P., Prieur F.P., Bronner M., Sokolowska J., Coulet F., Boutry-Kryza N., Calender A., Giraud S., Leone M., Fert-Ferrer S., Stoppa-Lyonnet D., Jiao Y., Lesueur F.L., Mebirouk N., Barouk-Simonet E., Bubien V., Longy M., Sevenet N., Gladieff L., Toulas C., Reimineras A., Sobol H., Paillerets B.B.-D., Cabaret O., Caron O., Guillaud-Bataille M., Rouleau E., Belotti M., Buecher B., Caputo S., Colas C., Pauw A.D., Fourme E., Gauthier-Villars M., Golmard L., Moncoutier V., Saule C., Donaldson A., Murray A., Brady A., Brewer C., Pottinger C., Miller C., Gallagher D., Gregory H., Cook J., Eason J., Adlard J., Barwell J., Ong K.-R., Snape K., Walker L., Izatt L., Side L., Tischkowitz M., Rogers M.T., Porteous M.E., Ahmed M., Morrison P.J., Brennan P., Eeles R., Davidson R., Collee J.M., Cornelissen S., Couch F.J., Cox A., Cross S.S., Cybulski C., Czene K., Daly M.B., de la Hoya M., Devilee P., Diez O., Ding Y.C., Dite G.S., Domchek S.M., Dork T., dos-Santos-Silva I., Droit A., Dubois S., Dumont M., Duran M., Durcan L., Dwek M., Eccles D.M., Engel C., Eriksson M., Evans D.G., Fasching P.A., Fletcher O., Floris G., Flyger H., Foretova L., Foulkes W.D., Friedman E., Fritschi L., Frost D., Gabrielson M., Gago-Dominguez M., Gambino G., Ganz P.A., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Georgoulias V., Giles G., Glendon G., Godwin A.K., Goldberg M.S., Goldgar D.E., Gonzalez-Neira A., Tibiletti M.G., Greene M.H., Grip M., Gronwald J., Grundy A., Guenel P., Hahnen E., Haiman C.A., Hakansson N., Hall P., Hamann U., Harrington P.A., Hartikainen J.M., Hartman M., He W., Healey C.S., Heemskerk-Gerritsen B.A.M., Heyworth J., Hillemanns P., Hogervorst F.B.L., Hollestelle A., Hooning M., Hopper J., Howell A., Huang G., Hulick P.J., Imyanitov E.N., Sexton A., Christian A., Trainer A., Spigelman A., Fellows A., Shelling A., Fazio A.D., Blackburn A., Crook A., Meiser B., Patterson B., Clarke C., Saunders C., Hunt C., Amor D., Marsh D., Edkins E., Salisbury E., Haan E., Neidermayr E., Macrea F., Farshid G., Lindeman G., Trench G., Mann G., Gill G., Thorne H., Hickie I., Winship I., Flanagan J., Kollias J., Visvader J., Stone J., Burke J., Saunus J., Forbes J., French J., Tucker K., Wu K., Phillips K., Lipton L., Andrews L., Lobb L., Kentwell M., Spurdle M., Cummings M., Gleeson M., Jenkins M., Young M.A., Delatycki M., Wallis M., Burgess M., Price M., Brown M., Southey M., Bogwitz M., Field M., Friedlander M., Gattas M., Saleh M., Hayward N., Pachter N., Cohen P., Duijf P., James P., Simpson P., Fong P., Butow P., Williams R., Kefford R., Scott R., Milne R.L., Balleine R., Dawson S.-J., Lok S., O'Connell S., Greening S., Nightingale S., Edwards S., Fox S., McLachlan S.-A., Lakhani S., Antill Y., Aalfs C., Meijers-Heijboer H., van Engelen K., Gille H., Boere I., Collee M., van Deurzen C., Obdeijn I.-M., van den Ouweland A., Seynaeve C., Siesling S., Verloop J., van Asperen C., van Cronenburg T., Blok R., de Boer M., Garcia E.G., Adank M., Hogervorst F., Jenner D., van Leeuwen F., Rookus M., Russell N., Schmidt M., van den Belt-Dusebout S., Kets C., Mensenkamp A., de Bock T., van der Hout A., Mourits M., Oosterwijk J., Ausems M., Koudijs M., Baxter R., Yip D., Carpenter J., Davis A., Pathmanathan N., Graham D., Sachchithananthan M., Isaacs C., Iwasaki M., Jager A., Jakimovska M., Jakubowska A., Janavicius R., Jankowitz R.C., John E.M., Johnson N., Jones M.E., Jukkola-Vuorinen A., Jung A., Kaaks R., Kang D., Kapoor P.M., Karlan B.Y., Keeman R., Kerin M.J., Khusnutdinova E., Kiiski J.I., Kirk J., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Kosma V.-M., Koutros S., Kubelka-Sabit K., Kwong A., Kyriacou K., Laitman Y., Lambrechts D., Lee E., Leslie G., Lester J., Lesueur F., Lindblom A., Lo W.-Y., Long J., Lophatananon A., Loud J.T., Lubinski J., MacInnis R.J., Maishman T., Makalic E., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matsuo K., Maurer T., Mavroudis D., Mayes R., McGuffog L., McLean C., Meindl A., Miller A., Miller N., Montagna M., Moreno F., Muir K., Mulligan A.M., Munoz-Garzon V.M., Muranen T.A., Narod S.A., Nassir R., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Nielsen F.C., Nikitina-Zake L., Norman A., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Osorio A., Pankratz V.S., Papp J., Park S.K., Park-Simon T.-W., Parsons M.T., Paul J., Pedersen I.S., Peissel B., Peshkin B., Peterlongo P., Peto J., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Presneau N., Prokofyeva D., Pujana M.A., Pylkas K., Radice P., Canzian F., Rantala J., Rau-Murthy R., Rennert G., Risch H.A., Robson M., Romero A., Rossing M., Saloustros E., Sanchez-Herrero E., Sandler D.P., Santamarina M., Sawyer E.J., Scheuner M.T., Schmidt D.F., and Schmutzler R.K.

Abstract

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2020

5. Online decision support for persons having a genetic predisposition to cancer and their partners during reproductive decision-making

Author

Reumkens, K., Tummers, M.H.E., Gietel-Habets, J.J., Kuijk, S.M.J. Van, Aalfs, C.M., Asperen, C.J. van, Ausems, M., Collee, M., Dommering, C.J., Kets, C.M., Kolk, L.E. van der, Oosterwijk, J.C, Tjan-Heijnen, V.C., Weijden, T. van der, Die-Smulders, C.E. de, Osch, L. van, Reumkens, K., Tummers, M.H.E., Gietel-Habets, J.J., Kuijk, S.M.J. Van, Aalfs, C.M., Asperen, C.J. van, Ausems, M., Collee, M., Dommering, C.J., Kets, C.M., Kolk, L.E. van der, Oosterwijk, J.C, Tjan-Heijnen, V.C., Weijden, T. van der, Die-Smulders, C.E. de, and Osch, L. van

Abstract

Contains fulltext : 206708.pdf (publisher's version ) (Open Access), A nationwide pretest-posttest study was conducted in all clinical genetic centres in the Netherlands, to evaluate the effects of an online decision aid to support persons who have a genetic predisposition to cancer and their partners in making an informed decision regarding reproductive options. Main outcomes (decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy) were measured before use (T0), immediately after use (T1), and at 2 weeks (T2) after use of the decision aid. Paired sample t tests were used to compute differences between the first and subsequent measurements. T0-T1 and T0-T2 comparisons indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict. Furthermore, use of the decision aid resulted in increased knowledge levels and improved realistic expectations. Level of deliberation only increased for participants with lower baseline levels of deliberation. Decision self-efficacy increased for those with low baseline scores, whereas those with high baseline scores showed a reduction at T2. It can be concluded that use of the decision aid resulted in several positive outcomes indicative of informed decision-making. The decision aid is an appropriate and highly appreciated tool to be used in addition to reproductive counseling.

Published
2019

6. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author

Wu, L. (Lang), Shi, W. (Wei), Long, J. (Jirong), Guo, X. (Xingyi), Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Bolla, M. K. (Manjeet K.), Shu, X.-O. (Xiao-Ou), Lu, Y. (Yingchang), Cai, Q. (Qiuyin), Al-Ejeh, F. (Fares), Rozali, E. (Esdy), Wang, Q. (Qin), Dennis, J. (Joe), Li, B. (Bingshan), Zeng, C. (Chenjie), Feng, H. (Helian), Gusev, A. (Alexander), Barfield, R. T. (Richard T.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Barrdahl, M. (Myrto), Baynes, C. (Caroline), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L. (Louise), Broberg, P. (Per), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Canzian, F. (Federico), Carter, B. D. (Brian D.), Castelao, J. E. (J. Esteban), Chang-Claude, J. (Jenny), Chen, X. (Xiaoqing), Cheng, T. D. (Ting-Yuan David), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, M. (Margriet), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, D. (David), Cox, A. (Angela), Cross, S. S. (Simon S.), Cunningham, J. M. (Julie M.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doheny, K. F. (Kimberly F.), Dork, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Eilber, U. (Ursula), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Fachal, L. (Laura), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Harrington, P. (Patricia), Hein, A. (Alexander), Hicks, B. (Belynda), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, K. (Kristine), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kosma, V.-M. (Veli-Matti), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Lubinski, J. (Jan), Luccarini, C. (Craig), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manson, J. E. (Joann E.), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Meijers-Heijboer, H. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Meyer, J. (Jeffery), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olopade, O. I. (Olufunmilayo I.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rahman, N. (Nazneen), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Romm, J. (Jane), Rudolph, A. (Anja), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, R. J. (Rodney J.), Scott, C. G. (Christopher G.), Seal, S. (Sheila), Shah, M. (Mitul), Shrubsole, M. J. (Martha J.), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. (William), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tessier, D. C. (Daniel C.), Thomas, A. (Abigail), Thone, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Torres, D. (Diana), Truong, T. (Therese), Untch, M. (Michael), Vachon, C. (Celine), Van den Berg, D. (David), Vincent, D. (Daniel), Waisfisz, Q. (Quinten), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. C. (Walter C.), Winqvist, R. (Robert), Wolk, A. (Alicja), Xia, L. (Lucy), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Ziv, E. (Elad), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Simard, J. (Jacques), Milne, R. L. (Roger L.), Edwards, S. L. (Stacey L.), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), Zheng, W. (Wei), Wu, L. (Lang), Shi, W. (Wei), Long, J. (Jirong), Guo, X. (Xingyi), Michailidou, K. (Kyriaki), Beesley, J. (Jonathan), Bolla, M. K. (Manjeet K.), Shu, X.-O. (Xiao-Ou), Lu, Y. (Yingchang), Cai, Q. (Qiuyin), Al-Ejeh, F. (Fares), Rozali, E. (Esdy), Wang, Q. (Qin), Dennis, J. (Joe), Li, B. (Bingshan), Zeng, C. (Chenjie), Feng, H. (Helian), Gusev, A. (Alexander), Barfield, R. T. (Richard T.), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Auer, P. L. (Paul L.), Barrdahl, M. (Myrto), Baynes, C. (Caroline), Beckmann, M. W. (Matthias W.), Benitez, J. (Javier), Bermisheva, M. (Marina), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia V.), Bojesen, S. E. (Stig E.), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Brinton, L. (Louise), Broberg, P. (Per), Brucker, S. Y. (Sara Y.), Burwinkel, B. (Barbara), Caldes, T. (Trinidad), Canzian, F. (Federico), Carter, B. D. (Brian D.), Castelao, J. E. (J. Esteban), Chang-Claude, J. (Jenny), Chen, X. (Xiaoqing), Cheng, T. D. (Ting-Yuan David), Christiansen, H. (Hans), Clarke, C. L. (Christine L.), Collee, M. (Margriet), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, D. (David), Cox, A. (Angela), Cross, S. S. (Simon S.), Cunningham, J. M. (Julie M.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Doheny, K. F. (Kimberly F.), Dork, T. (Thilo), dos-Santos-Silva, I. (Isabel), Dumont, M. (Martine), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Eilber, U. (Ursula), Eliassen, A. H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Fachal, L. (Laura), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Fritschi, L. (Lin), Gabrielson, M. (Marike), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garcia-Closas, M. (Montserrat), Gaudet, M. M. (Mia M.), Ghoussaini, M. (Maya), Giles, G. G. (Graham G.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Guenel, P. (Pascal), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hakansson, N. (Niclas), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Harrington, P. (Patricia), Hein, A. (Alexander), Hicks, B. (Belynda), Hillemanns, P. (Peter), Hollestelle, A. (Antoinette), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Huang, G. (Guanmengqian), Humphreys, K. (Keith), Hunter, D. J. (David J.), Jakubowska, A. (Anna), Janni, W. (Wolfgang), John, E. M. (Esther M.), Johnson, N. (Nichola), Jones, K. (Kristine), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kerin, M. J. (Michael J.), Khusnutdinova, E. (Elza), Kosma, V.-M. (Veli-Matti), Kristensen, V. N. (Vessela N.), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Li, J. (Jingmei), Lindstrom, S. (Sara), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loibl, S. (Sibylle), Lubinski, J. (Jan), Luccarini, C. (Craig), Lux, M. P. (Michael P.), MacInnis, R. J. (Robert J.), Maishman, T. (Tom), Kostovska, I. M. (Ivana Maleva), Mannermaa, A. (Arto), Manson, J. E. (Joann E.), Margolin, S. (Sara), Mavroudis, D. (Dimitrios), Meijers-Heijboer, H. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Meyer, J. (Jeffery), Mulligan, A. M. (Anna Marie), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Nielsen, S. F. (Sune F.), Nordestgaard, B. G. (Borge G.), Olopade, O. I. (Olufunmilayo I.), Olson, J. E. (Janet E.), Olsson, H. (Hakan), Peterlongo, P. (Paolo), Peto, J. (Julian), Plaseska-Karanfilska, D. (Dijana), Prentice, R. (Ross), Presneau, N. (Nadege), Pylkäs, K. (Katri), Rack, B. (Brigitte), Radice, P. (Paolo), Rahman, N. (Nazneen), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Rhenius, V. (Valerie), Romero, A. (Atocha), Romm, J. (Jane), Rudolph, A. (Anja), Saloustros, E. (Emmanouil), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Schmidt, M. K. (Marjanka K.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Scott, R. J. (Rodney J.), Scott, C. G. (Christopher G.), Seal, S. (Sheila), Shah, M. (Mitul), Shrubsole, M. J. (Martha J.), Smeets, A. (Ann), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Surowy, H. (Harald), Swerdlow, A. J. (Anthony J.), Tamimi, R. M. (Rulla M.), Tapper, W. (William), Taylor, J. A. (Jack A.), Terry, M. B. (Mary Beth), Tessier, D. C. (Daniel C.), Thomas, A. (Abigail), Thone, K. (Kathrin), Tollenaar, R. A. (Rob A. E. M.), Torres, D. (Diana), Truong, T. (Therese), Untch, M. (Michael), Vachon, C. (Celine), Van den Berg, D. (David), Vincent, D. (Daniel), Waisfisz, Q. (Quinten), Weinberg, C. R. (Clarice R.), Wendt, C. (Camilla), Whittemore, A. S. (Alice S.), Wildiers, H. (Hans), Willett, W. C. (Walter C.), Winqvist, R. (Robert), Wolk, A. (Alicja), Xia, L. (Lucy), Yang, X. R. (Xiaohong R.), Ziogas, A. (Argyrios), Ziv, E. (Elad), Dunning, A. M. (Alison M.), Pharoah, P. D. (Paul D. P.), Simard, J. (Jacques), Milne, R. L. (Roger L.), Edwards, S. L. (Stacey L.), Kraft, P. (Peter), Easton, D. F. (Douglas F.), Chenevix-Trench, G. (Georgia), and Zheng, W. (Wei)

Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10−6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

Published
2018

7. RAD51B in familial breast cancer.

Author

Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Anderson L., Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., and Anderson L.

Abstract

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

Published
2017

8. RAD51B in Familial Breast Cancer

Author

Brusgaard, K, Pelttari, LM, Khan, S, Vuorela, M, Kiiski, JI, Vilske, S, Nevanlinna, V, Ranta, S, Schleutker, J, Winqvist, R, Kallioniemi, A, Doerk, T, Bogdanova, NV, Figueroa, J, Pharoah, PDP, Schmidt, MK, Dunning, AM, Garcia-Closas, M, Bolla, MK, Dennis, J, Michailidou, K, Wang, Q, Hopper, JL, Southey, MC, Rosenberg, EH, Fasching, PA, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Surowy, H, Guenel, P, Truong, T, Bojesen, SE, Nordestgaard, BG, Benitez, J, Gonzalez-Neira, A, Neuhausen, SL, Anton-Culver, H, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Bruening, T, Lindblom, A, Margolin, S, Mannermaa, A, Hartikainen, JM, Chenevix-Trench, G, Van Dyck, L, Janssen, H, Chang-Claude, J, Rudolph, A, Radice, P, Peterlongo, P, Hallberg, E, Olson, JE, Giles, GG, Milne, RL, Haiman, CA, Schumacher, F, Simard, J, Dumont, M, Kristensen, V, Borresen-Dale, A-L, Zheng, W, Beeghly-Fadiel, A, Grip, M, Andrulis, IL, Glendon, G, Devilee, P, Seynaeve, C, Hooning, MJ, Collee, M, Cox, A, Cross, SS, Shah, M, Luben, RN, Hamann, U, Torres, D, Jakubowska, A, Lubinski, J, Couch, FJ, Yannoukakos, D, Orr, N, Swerdlow, A, Darabi, H, Li, J, Czene, K, Hall, P, Easton, DF, Mattson, J, Blomqvist, C, Aittomaki, K, Nevanlinna, H, Brusgaard, K, Pelttari, LM, Khan, S, Vuorela, M, Kiiski, JI, Vilske, S, Nevanlinna, V, Ranta, S, Schleutker, J, Winqvist, R, Kallioniemi, A, Doerk, T, Bogdanova, NV, Figueroa, J, Pharoah, PDP, Schmidt, MK, Dunning, AM, Garcia-Closas, M, Bolla, MK, Dennis, J, Michailidou, K, Wang, Q, Hopper, JL, Southey, MC, Rosenberg, EH, Fasching, PA, Beckmann, MW, Peto, J, dos-Santos-Silva, I, Sawyer, EJ, Tomlinson, I, Burwinkel, B, Surowy, H, Guenel, P, Truong, T, Bojesen, SE, Nordestgaard, BG, Benitez, J, Gonzalez-Neira, A, Neuhausen, SL, Anton-Culver, H, Brenner, H, Arndt, V, Meindl, A, Schmutzler, RK, Brauch, H, Bruening, T, Lindblom, A, Margolin, S, Mannermaa, A, Hartikainen, JM, Chenevix-Trench, G, Van Dyck, L, Janssen, H, Chang-Claude, J, Rudolph, A, Radice, P, Peterlongo, P, Hallberg, E, Olson, JE, Giles, GG, Milne, RL, Haiman, CA, Schumacher, F, Simard, J, Dumont, M, Kristensen, V, Borresen-Dale, A-L, Zheng, W, Beeghly-Fadiel, A, Grip, M, Andrulis, IL, Glendon, G, Devilee, P, Seynaeve, C, Hooning, MJ, Collee, M, Cox, A, Cross, SS, Shah, M, Luben, RN, Hamann, U, Torres, D, Jakubowska, A, Lubinski, J, Couch, FJ, Yannoukakos, D, Orr, N, Swerdlow, A, Darabi, H, Li, J, Czene, K, Hall, P, Easton, DF, Mattson, J, Blomqvist, C, Aittomaki, K, and Nevanlinna, H

Abstract

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

Published
2016

9. Variation in Mutation Spectrum Partly Explains Regional Differences in the Breast Cancer Risk of Female BRCA Mutation Carriers in the Netherlands

Author

Vos, J.R., Teixeira, N., Kolk, D.M. van der, Mourits, M.J.E., Rookus, M.A., Leeuwen, F.E. van, Collee, M., Asperen, C.J. van, Mensenkamp, A.R., Ausems, M.G.E.M., Os, T.A.M. van, Meijers-Heijboer, H.E.J., Gomez-Garcia, E.B., Vasen, H.F., Brohet, R.M., Hout, A.H. van der, Jansen, L., Oosterwijk, J.C., Bock, G.H. de, Hereditary Breast Ovarian Canc Res, Human genetics, CCA - Oncogenesis, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Targeted Gynaecologic Oncology (TARGON), Klinische Genetica, Genetica en Celbiologie, Family Medicine, RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Human Genetics, CCA -Cancer Center Amsterdam, and ARD - Amsterdam Reproduction and Development

Subjects
medicine.medical_specialty, PENETRANCE, endocrine system diseases, Epidemiology, Population, REDUCING SALPINGO-OOPHORECTOMY, Breast Neoplasms, OVARIAN-CANCER, FAMILIES, Cohort Studies, Breast cancer, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, POSITION, education, skin and connective tissue diseases, Netherlands, BRCA2 Protein, Gynecology, education.field_of_study, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], business.industry, Hazard ratio, BRCA mutation, Cancer, Odds ratio, medicine.disease, SERIES, Penetrance, Oncology, Mutation, Female, business, Demography, Cohort study
Abstract

Background: We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) older than 60 in the Northern Netherlands, and to analyze whether these could be explained by mutation spectrum or population background risk. Methods: This consecutive cohort study included all known pathogenic BRCA1/2 carriers in the Northern Netherlands (N = 1,050). Carrier and general reference populations were: BRCA1/2 carriers in the rest of the Netherlands (N = 2,013) and the general population in both regions. Regional differences were assessed with HRs and ORs. HRs were adjusted for birth year and mutation spectrum. Results: All BRCA1 carriers and BRCA2 carriers younger than 60 had a significantly lower breast cancer risk in the Northern Netherlands; HRs were 0.66 and 0.64, respectively. Above age 60, the breast cancer risk in BRCA2 carriers in the Northern Netherlands was higher than in the rest of the Netherlands [HR, 3.99; 95% confidence interval (CI), 1.11–14.35]. Adjustment for mutational spectrum changed the HRs for BRCA1, BRCA2 Conclusions: Differences in mutation spectrum only partly explain the regional differences in breast cancer risk in BRCA2 carriers, and for an even smaller part in BRCA1 carriers. Impact: The increased risk in BRCA2 carriers older than 60 may warrant extension of intensive breast screening beyond age 60. Cancer Epidemiol Biomarkers Prev; 23(11); 2482–91. ©2014 AACR.

Published
2014
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10. Comparison of 6q25 Breast Cancer Hits from Asian and\ud European Genome Wide Association Studies in the\ud Breast Cancer Association Consortium (BCAC)

Author

Hein, R., Maranian, M., Hopper, J.L., Kapuscinski, M.K., Southey, M.C., Park, D.J., Schmidt, M.K., Broeks, A., Hogervorst, F.B.L., Bueno-de-Mesquit, H.B., Muir, K.R., Lophatananon, A., Rattanamongkongul, S., Puttawibul, P., Fasching, P.A., Hein, A., Ekici, A.B., Beckmann, M.W., Fletcher, O., Johnson, N., Silva, I.D.S., Peto, J., Sawyer, E., Tomlinson, I., Kerin, M., Miller, N., Marmee, F., Schneeweiss, A., Sohn, C., Burwinkel, B., Guenel, P., Cordina-Duverger, E., Menegaux, F., Truong, T., Bojesen, S.E., Nordestgaard, B.G., Flyger, H., Milne, R.L., Arias Perez, J.I., Pilar Zamora, M., Benitez, J., Anton-Culver, H., Ziogas, A., Bernstein, L., Clarke, C.A., Brenner, H., Mueller, H., Arndt, V., Stegmaier, C., Rahman, N., Seal, S., Turnbull, C., Renwick, A., Meindl, A., Schott, S., Bartram, C.R., Schmutzler, R.K., Brauch, H., Hamann, U., Ko, Y-D., Wang-Gohrke, S., Doerk, T., Schuermann, P., Karstens, J.H., Hillemanns, P., Nevanlinna, H., Heikkinen, T., Aittomaki, K., Blomqvist, C., Bogdanova, N.V., Zalutsky, I.V., Antonenkova, N.N., Bermisheva, M., Prokovieva, D., Farahtdinova, A., Khusnutdinova, E., Lindblom, A., Margolin, S., Mannermaa, A., Kataja, V., Kosma, V-M., Hartikainen, J., Chen, X., Beesley, J., Lambrechts, D., Zhao, H., Neven, P., Wildiers, H., Nickels, S., Flesch-Janys, D., Radice, P., Peterlongo, P., Manoukian, S., Barile, M., Couch, F.J., Olson, J.E., Wang, X., Fredericksen, Z., Giles, G.G., Baglietto, L., McLean, C.A., Severi, G., Offit, K., Robson, M., Gaudet, M.M., Vijai, J., Alnaes, G.G., Kristensen, V., Borresen-Dale, A-L., John, E.M., Miron, A., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Grip, M., Andrulis, I.L., Knight, J.A., Glendon, G., Mulligan, A.M., Figueroa, J.D., Garcia-Closas, M., Lissowska, J., Sherman, M.E., Hooning, M., Martens, J.W.M., Seynaeve, C., Collee, M., Hall, P., Humpreys, K., Czene, K., Liu, J., Cox, A., Brock, I.W., Cross, S.S., Reed, M.W.R., Ahmed, S., Ghoussaini, M., Pharoah, P.D.P., Kang, D., Yoo, K-Y., Noh, D-Y., Jakubowska, A., Jaworska, K., Durda, K., Zlowocka, E., Sangrajrang, S., Gaborieau, V., Brennan, P., McKay, J., Shen, C-Y., Yu, J-C., Hsu, H-M., Hou, M-F., Orr, N., Schoemaker, M., Ashworth, A., Swerdlow, A., Trentham-Dietz, A., Newcomb, P.A., Titus, L., Egan, K.M., Chenevix-Trench, G., Antoniou, A.C., Humphreys, M.K., Morrison, J., Chang-Claude, J., Easton, D.F., Dunning, A.M., Network, GENICA, Investigators, K, and Group, AOCS

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single\ud nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports\ud about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP,\ud tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from fortyfour\ud studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European\ud descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were\ud used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER2) tumours. Models including both SNPs\ud were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer\ud risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26–\ud 1.48), p = 7.6610214 in Asians and 1.09 (95% CI 1.07–1.11), p = 6.8610218 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI\ud 1.19–1.41), p = 1.261029 in Asians and 1.12 (95% CI 1.08–1.17), p = 3.861029 in Europeans]. SNP rs2046210 is associated with a\ud significantly greater risk of ER2 than ER+ tumours in Europeans [OR (ER2) = 1.20 (95% CI 1.15–1.25), p = 1.8610217 versus OR\ud (ER+) = 1.07 (95% CI 1.04–1.1), p = 1.361027\ud , pheterogeneity = 5.161026\ud ]. In these Asian studies, by contrast, there is no clear\ud evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other\ud SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in\ud Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER2 tumours.

Published
2012

11. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

Author

Cox, D. G., Simard, J., Sinnett, D., Hamdi, Y., Soucy, P., Ouimet, M., Barjhoux, L., Verny-Pierre, C., McGuffog, L., Healey, S., Szabo, C., Greene, M. H., Mai, P. L., Andrulis, I. L., Thomassen, M., Gerdes, A.-M., Caligo, M. A., Friedman, E., Laitman, Y., Kaufman, B., Paluch, S. S., Borg, A., Karlsson, P., Stenmark Askmalm, M., Barbany Bustinza, G., Nathanson, K. L., Domchek, S. M., Rebbeck, T. R., Benitez, J., Hamann, U., Rookus, M. A., van den Ouweland, A. M. W., Ausems, M. G. E. M., Aalfs, C. M., van Asperen, C. J., Devilee, P., Gille, H. J. J. P., Peock, S., Frost, D., Evans, D. G., Eeles, R., Izatt, L., Adlard, J., Paterson, J., Eason, J., Godwin, A. K., Remon, M.-A., Moncoutier, V., Gauthier-Villars, M., Lasset, C., Giraud, S., Hardouin, A., Berthet, P., Sobol, H., Eisinger, F., Bressac de Paillerets, B., Caron, O., Delnatte, C., Goldgar, D., Miron, A., Ozcelik, H., Buys, S., Southey, M. C., Terry, M. B., Singer, C. F., Dressler, A.-C., Tea, M.-K., Hansen, T. V. O., Johannsson, O., Piedmonte, M., Rodriguez, G. C., Basil, J. B., Blank, S., Toland, A. E., Montagna, M., Isaacs, C., Blanco, I., Gayther, S. A., Moysich, K. B., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Niederacher, D., Sutter, C., Gadzicki, D., Fiebig, B., Caldes, T., Laframboise, R., Nevanlinna, H., Chen, X., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Couch, F. J., Wang, X., Peterlongo, P., Manoukian, S., Bernard, L., Radice, P., Easton, D. F., Chenevix-Trench, G., Antoniou, A. C., Stoppa-Lyonnet, D., Mazoyer, S., Sinilnikova, O. M., Dumont, M., Greene, M., Glendon, G., Selander, T., Weerasooriya, N., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark-Askmalm, M., Liedgren, S., Loman, N., Olsson, H., Kristoffersson, U., Soller, M., Jernstrom, H., Harbst, K., Henriksson, K., Lindblom, A., Arver, B., von Wachenfeldt, A., Liljegren, A., Barbany-Bustinza, G., Rantala, J., Melin, B., Gronberg, H., Stattin, E.-L., Emanuelsson, M., Ehrencrona, H., Torres, D., Rashid, M. U., Seidel-Renkert, A., Hogervorst, F. B. L., Verhoef, S., Verheus, M., van't Veer, L. J., van Leeuwen, F. E., Collee, M., Jager, A., Hooning, M. J., Tilanus-Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., van der Luijt, R. B., van Os, T. A., Gille, J. J. P., Waisfisz, Q., Meijers-Heijboer, H. E. J., Gomez-Garcia, E. B., van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., van der Hout, A. H., Mourits, M. J., Vasen, H. F., Cook, M., Platte, R., Miedzybrodzka, Z., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Ong, K.-r., Hoffman, J., Donaldson, A., James, M., Downing, S., Taylor, A., Murray, A., Rogers, M. T., McCann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Davidson, R., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Lalloo, F., Taylor, J., Side, L., Male, A., Berlin, C., Collier, R., Douglas, F., Claber, O., Jobson, I., Walker, L., McLeod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern-Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Cook, J., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Eccles, D., Lucassen, A., Crawford, G., McBride, D., Smalley, S., Sinilnikova, O., Leone, M., Buecher, B., Houdayer, C., Belotti, M., Tirapo, C., de Pauw, A., Bressac-de-Paillerets, B., Remenieras, A., Byrde, V., Lenoir, G., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Bourdon, V., Noguchi, T., Coulet, F., Colas, C., Soubrier, F., Coupier, I., Pujol, P., Peyrat, J.-P., Fournier, J., Revillion, F., Vennin, P., Adenis, C., Rouleau, E., Lidereau, R., Demange, L., Nogues, C., Muller, D., Fricker, J.-P., Longy, M., Sevenet, N., Toulas, C., Guimbaud, R., Gladieff, L., Feillel, V., Leroux, D., Dreyfus, H., Rebischung, C., Coron, F., Faivre, L., Prieur, F., Lebrun, M., Ferrer, S. F., Frenay, M., Venat-Bouvet, L., Mortemousque, I., Lynch, H. T., Snyder, C. L., Ejlertsen, B., Andersen, M. K., Kjaergaard, S., Senter, L., Sweet, K., O'Connor, M., Craven, C., Pharoah, P., Ramus, S., Pye, C., Harrington, P., Wozniak, E., Varon-Mateeva, R., Kast, K., Preisler-Adams, S., Deissler, H., Schonbuchner, I., Heinritz, W., Schafer, D., Aittomaki, K., Blomqvist, C., Heikkinen, T., Erkkila, R. N. I., Thorne, H., Niedermayr, E., de la Hoya, M., Perez-Segura, P., Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Department of Pediatrics, CHU Sainte Justine [Montréal], Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Queensland Institute of Medical Research, University of Delaware [Newark], Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Clinical Genetics, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Department of Oncology, Sahlgrenska University Hospital [Gothenburg], Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Molecular Genetics of Breast Cancer, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Addenbrookes Hospital, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, génétique, Institut Curie [Paris], Service de Génétique Oncologique, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Consultation d'Oncogénétique, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre René Gauducheau, CRLCC René Gauducheau, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Internal Medicine, Huntsman Cancer Institute, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Faculty of Medicine, University of Iceland [Reykjavik], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Lombardi Comprehensive Cancer Center, Georgetown University, Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig [Leipzig], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Heidelberg University Hospital [Heidelberg], Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Universität Regensburg (UR), Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Laboratory Medicine and Pathology, Mayo Clinic, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 6, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Centre, CHU Ste Justine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Génétique moléculaire, signalisation et cancer (GMSC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Human Genetics, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Tel Aviv University (TAU), University of Pennsylvania-University of Pennsylvania, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Roswell Park Cancer Institute [Buffalo] (RPCI), Georgetown University [Washington] (GU), Universität Leipzig, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Génétique moléculaire, signalisation et cancer ( GMSC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Cambridge [UK] ( CAM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), Sahlgrenska University Hospital, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Deutsches Krebsforschungszentrum ( DKFZ ), INSTITUT CURIE, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre François Baclesse, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Mount Sinai Hospital ( MSH ), Medical University of Vienna-Department of OB/GYN, Medical University of Vienna, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximilians-Universität München, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Hannover Medical School [Hannover] ( MHH ), University Regensburg, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Human genetics, and CCA - Oncogenesis

Subjects
endocrine system diseases, Electrophoretic Mobility Shift Assay, MESH : Breast Neoplasms, medicine.disease_cause, Linkage Disequilibrium, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Genes, Reporter, Risk Factors, MESH: Risk Factors, Genotype, MESH : Female, Luciferases, skin and connective tissue diseases, Genetics (clinical), MESH: Genetic Association Studies, MESH: Heterozygote, Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Genes, Reporter, MESH : Risk Factors, 3. Good health, MESH: Linkage Disequilibrium, 030220 oncology & carcinogenesis, MESH : Electrophoretic Mobility Shift Assay, Female, Breast disease, MESH : Mutation, MESH : Heterozygote, Heterozygote, MESH: Mutation, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, medicine, Humans, MESH : BRCA1 Protein, MESH : HeLa Cells, Genetic Predisposition to Disease, ddc:610, Allele, Molecular Biology, MESH : Haplotypes, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: BRCA1 Protein, MESH : Luciferases, MESH: Humans, Hereditary cancer and cancer-related syndromes [ONCOL 1], MESH: Alleles, Haplotype, MESH : Humans, MESH: Genes, Reporter, Cancer, MESH : Genetic Association Studies, MESH: Haplotypes, medicine.disease, Haplotypes, Mutation, MESH: Electrophoretic Mobility Shift Assay, MESH: HeLa Cells, Cancer research, MESH : Genetic Predisposition to Disease, MESH: Luciferases, Carcinogenesis, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms, HeLa Cells
Abstract

Item does not contain fulltext Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

Published
2011
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12. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author

Antoniou, A. C., Kartsonaki, C., Sinilnikova, O. M., Soucy, P., Mcguffog, L., Healey, S., Lee, A., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Cattaneo, E., Barile, M., Pensotti, V., Pasini, B., Dolcetti, R., Giannini, Giuseppe, Laura Putignano, A., Varesco, L., Radice, P., Mai, P. L., Greene, M. H., Andrulis, I. L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A. M., Kruse, T. A., Jensen, U. B., Cruger, D. G., Caligo, M. A., Laitman, Y., Milgrom, R., Kaufman, B., Paluch Shimon, S., Friedman, E., Loman, N., Harbst, K., Lindblom, A., Arver, B., Ehrencrona, H., Melin, B., Nathanson, K. L., Domchek, S. M., Rebbeck, T., Jakubowska, A., Lubinski, J., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Gorski, B., Osorio, A., Cajal, T. R., Fostira, F., Andres, R., Benitez, J., Hamann, U., Hogervorst, F. B., Rookus, M. A., Hooning, M. J., Nelen, M. R., Van Der Luijt, R. B., Van Os, T. A. M., Van Asperen, C. J., Devilee, P., Meijers Heijboer, H. E. J., Garcia, E. B. G., Peock, S., Cook, M., Frost, D., Platte, R., Leyland, J., Evans, D. G., Lalloo, F., Eeles, R., Izatt, L., Adlard, J., Davidson, R., Eccles, D., Ong, K. R., Cook, J., Douglas, F., Paterson, J., John Kennedy, M., Miedzybrodzka, Z., Godwin, A., Stoppa Lyonnet, D., Buecher, B., Belotti, M., Tirapo, C., Mazoyer, S., Barjhoux, L., Lasset, C., Leroux, D., Faivre, L., Bronner, M., Prieur, F., Nogues, C., Rouleau, E., Pujol, P., Coupier, I., Frenay, M., Hopper, J. L., Daly, M. B., Terry, M. B., John, E. M., Buys, S. S., Yassin, Y., Miron, A., Goldgar, D., Singer, C. F., Tea, M. K., Pfeiler, G., Catharina Dressler, A., Hansen, T. V. O., Jonson, L., Ejlertsen, B., Barkardottir, R. B., Kirchhoff, T., Offit, K., Piedmonte, M., Rodriguez, G., Small, L., Boggess, J., Blank, S., Basil, J., Azodi, M., Toland, A. E., Montagna, M., Tognazzo, S., Agata, S., Imyanitov, E., Janavicius, R., Lazaro, C., Blanco, I., Pharoah, P. D. P., Sucheston, L., Karlan, B. Y., Walsh, C. S., Olah, E., Bozsik, A., Teo, S. H., Seldon, J. L., Beattie, M. S., Van Rensburg, E. J., Sluiter, M. D., Diez, O., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ruehl, I., Varon Mateeva, R., Kast, K., Deissler, H., Niederacher, D., Arnold, N., Gadzicki, D., Schonbuchner, I., Caldes, T., De La Hoya, M., Nevanlinna, H., Aittomaki, K., Dumont, M., Chiquette, J., Tischkowitz, M., Chen, X. Q., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Fredericksen, Z., Wang, X., Pankratz, V. S., Couch, F., Simard, J., Easton, D. F., Chenevix Trench, G., Karlsson, P., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark Askmalm, M., Liedgren, S., Borg, A., Olsson, H., Kristoffersson, U., Jernstrom, H., Henriksson, K., Von Wachenfeldt, A., Liljegren, A., Barbany Bustinza, G., Rantala, J., Gronberg, H., Stattin, E. L., Emanuelsson, M., Brandell, R. R., Dahl, N., Hogervorst, F. B. L., Verhoef, S., Verheus, M., Veer, L. V., Van Leeuwen, F. E., Collee, M., Van Den Ouweland, A. M. W., Jager, A., Tilanus Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., Aalfs, C. M., Van Os, T. A., Gille, J. J. P., Waisfisz, Q., Gomez Garcia, E. B., Van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., Van Der Hout, A. H., Mourits, M. J., Vasen, H. F., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Mckeown, C., Hoffman, J., Donaldson, A., Downing, S., Taylor, A., Murray, A., Rogers, M. T., Mccann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Taylor, J., Side, L., Male, A., Berlin, C., Eason, J., Collier, R., Claber, O., Jobson, I., Walker, L., Mcleod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Lucassen, A., Crawford, G., Mcbride, D., Smalley, S., University of Groningen, Clinical Genetics, Medical Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] ( CAM ), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Queensland Institute of Medical Research, Unit of Molecular Bases of Genetic Risk and Genetic Testing, Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare, Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumouri (INT), Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Consortium for Genomics Technology (Cogentech), Department of Genetics, Biology and Biochemistry, University of Turin, Cancer Bioimmunotherapy Unit, IRCCS-Centro di Riferimento Oncologico, Department of Experimental Medicine, Università degli Studi di Roma 'La Sapienza' [Rome], Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Unit of Hereditary Cancers, Istituto Nazionale per la Ricerca sul Cancro, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Ontario Cancer Genetics Network, Cancer Care Ontario, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Samuel Lunenfeld Research Institute, Mount Sinai Hospital ( MSH ), Department of Clinical Genetics, Odense University Hospital, Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Department of Oncology, Lund University Hospital, Karolinska University Hospital [Stockholm], Departament of Genetics and Pathology, Uppsala University-Rudbeck Laboratory, Department of Radiation Sciences and Oncology, Umeå University, Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine-Abramson Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, International Hereditary Cancer Center, Pomeranian Medical University, Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Department of Medical Oncology, Hospital Sant Pau, Medical Oncology Division, Hospital Clínico de Zaragoza, Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum ( DKFZ ), Department of Genetic Epidemiology, Leiden University Medical Center (LUMC), Genetic Medicine, Manchester Academic Health Sciences Centre-Central Manchester University Hospitals, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Guy's and St. Thomas' NHS Foundation Trust, Yorkshire Regional Genetics Service, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Wessex Clinical Genetics Service, Princess Anne Hospital, West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Addenbrookes Hospital, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), génétique, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe de prévention et épidémiologie génétique, Centre Léon Bérard [Lyon], Service d'onco-hématologie et génétique, CHU Grenoble, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Santé Publique, Hôpital René HUGUENIN (Saint-Cloud)-INSTITUT CURIE, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Institut de recherche en cancérologie de Montpellier ( IRCM - U896 Inserm - UM1 ), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Consultation d'oncogénétique, CRLCC Antoine Lacassagne, Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Department of Surgery, Harvard Medical School [Boston] ( HMS ), Department of Dermatology, University of Utah School of Medicine [Salt Lake City], Dept of OB/GYN and Comprehensive Cancer Center, Medical University of Vienna, Division of Special Gynecology, Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Rigshospitalet [Copenhagen], Department of Pathology, Landspitali-University Hospital, Department of Environmental Medicine, New York University School of Medicine-NYU Cancer Institute, Clinical Genetics Service, Memorial Sloane Kettering Cancer Center [New York], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, State Research Institute Innovative Medicine Center, Molecular Diagnostic Unit, IDIBELL-Catalan Institute of Oncology, Genetic Counselling Unit, Department of Molecular Genetics, National Institute of Oncology, Cancer Research Initiatives Foundation, Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre, Oncogenetics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Department of Gynaecology and Obstetrics, University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximillians University, Charite berlin, University Hospital Carl Gustav Carus, University Hospital Ulm, University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] ( MHH ), University of Würzburg, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Genetics, Portuguese Oncology Institute, Department of Medical Genetics, Mayo Clinic, Department of Laboratory Medicine and Pathology, Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Università degli studi di Torino = University of Turin (UNITO), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi di Firenze = University of Florence (UniFI), National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Mount Sinai Hospital [Toronto, Canada] (MSH), Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Tel Aviv University (TAU), Uppsala University, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Abramson Cancer Center-Perelman School of Medicine, International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM), Pomeranian Medical University [Szczecin] (PUM), Hospital de la Santa Creu i Sant Pau, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universiteit Leiden-Universiteit Leiden, Birmingham Women's and Children's NHS Foundation Trust, Sheffield Children's NHS Foundation Trust, Newcastle Upon Tyne Hospitals NHS Foundation Trust, University of Kansas Medical Center [Kansas City, KS, USA], Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Harvard Medical School [Boston] (HMS), Medizinische Universität Wien = Medical University of Vienna, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Department of Clinical Biochemistry [Rigshospitalet], Copenhagen University Hospital, New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute, Roswell Park Cancer Institute [Buffalo] (RPCI), Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE), Universität Leipzig, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universitätsklinikum Ulm - University Hospital of Ulm, University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), Hannover Medical School [Hannover] (MHH), Julius-Maximilians-Universität Würzburg (JMU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Kansas Medical Center [Lawrence], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital René HUGUENIN (Saint-Cloud)-Institut Curie [Paris], CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Universität Leipzig [Leipzig], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), University of Florence (UNIFI), Mount Sinai Hospital (MSH), Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Hôpital René HUGUENIN (Saint-Cloud), Technical University of Munich (TUM), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Human genetics, CCA - Oncogenesis, Human Genetics, Klinische Genetica, and RS: GROW - School for Oncology and Reproduction

Subjects
MESH : BRCA2 Protein, MESH : Aged, Estrogen receptor, Genome-wide association study, MESH : Breast Neoplasms, VARIANTS, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Chromosomes, Human, Pair 6, MESH: BRCA2 Protein, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Genotype, CONFER SUSCEPTIBILITY, Chromosomes, Human, MESH : Female, skin and connective tissue diseases, Genetics (clinical), POPULATION, MESH: Heterozygote, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Adult, Middle Aged, MESH : Risk Factors, 3. Good health, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, MESH : Mutation, Adult, MESH : Heterozygote, Heterozygote, MESH: Mutation, MESH: Chromosomes, Human, Pair 6, MESH: Chromosomes, Human, Pair 1, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Single-nucleotide polymorphism, Breast Neoplasms, Biology, MESH: Chromosomes, Human, Polymorphism, Single Nucleotide, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Genetics, medicine, LOCUS, SNP, Humans, MESH : Middle Aged, MESH : BRCA1 Protein, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, Molecular Biology, Alleles, MESH: BRCA1 Protein, 030304 developmental biology, Aged, BRCA2 Protein, MESH: Humans, 2Q35, MESH: Alleles, MESH : Humans, MESH: Adult, medicine.disease, MESH : Chromosomes, Human, ESTROGEN-RECEPTOR, Mutation, Cancer research, MESH : Genetic Predisposition to Disease, GENETIC MODIFIERS, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms
Abstract

Item does not contain fulltext Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

Published
2011
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13. Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study

Author

Wevers, MR, Schmidt, MK (Marjanka), Engelhardt, EG, Verhoef, S, Hooning, Maartje, Kriege, Mieke, Seynaeve, Caroline, Collee, M, van Asperen, CJ, Tollenaar, RAEM, Koppert, Linetta, Witkamp, AJ, Rutgers, EJT, Aaronson, NK, Rookus, MA, Ausems, MGEM, Wevers, MR, Schmidt, MK (Marjanka), Engelhardt, EG, Verhoef, S, Hooning, Maartje, Kriege, Mieke, Seynaeve, Caroline, Collee, M, van Asperen, CJ, Tollenaar, RAEM, Koppert, Linetta, Witkamp, AJ, Rutgers, EJT, Aaronson, NK, Rookus, MA, and Ausems, MGEM

Abstract

It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one's status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995-2000 versus 2001-2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76 %) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34 %, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.

Published
2015

14. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author

Chan, KYK, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Arias Perez, JI, Pilar Zamora, M, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, Y-D, Wang-Gohrke, S, Doerk, T, Schuermann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J, Chen, X, Beesley, J, Lambrechts, D, Zhao, H, Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JWM, Seynaeve, C, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S, Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, K-Y, Noh, D-Y, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, C-Y, Yu, J-C, Hsu, H-M, Hou, M-F, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, Chan, KYK, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Arias Perez, JI, Pilar Zamora, M, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, Y-D, Wang-Gohrke, S, Doerk, T, Schuermann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J, Chen, X, Beesley, J, Lambrechts, D, Zhao, H, Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JWM, Seynaeve, C, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S, Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, K-Y, Noh, D-Y, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, C-Y, Yu, J-C, Hsu, H-M, Hou, M-F, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, and Dunning, AM

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of

Published
2012

15. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author

Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, Marjanka K, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, ID, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JIA, Zamora, MP, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, YD, Wang-Gohrke, S, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chen, XQ, Beesley, J, Lambrechts, D, Zhao, H (Hui), Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, XS, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, John, Seynaeve, Caroline, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, JJ, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S (Shahana), Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Shen, CY, Yu, JC, Hsu, HM, Hou, MF, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, Truong, T, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, Marjanka K, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, ID, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JIA, Zamora, MP, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, YD, Wang-Gohrke, S, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chen, XQ, Beesley, J, Lambrechts, D, Zhao, H (Hui), Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, XS, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, John, Seynaeve, Caroline, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, JJ, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S (Shahana), Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Shen, CY, Yu, JC, Hsu, HM, Hou, MF, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, and Truong, T

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6x10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8x10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2x10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8x10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8x10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3x10(-7), p(heterogeneity) = 5.1x10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

Published
2012

16. Mutations in SMAD3 cause a syndromic form of aortic aneurysms and dissections with early-onset osteoarthritis

Author

Laar, I.M. van de, Oldenburg, R.A., Pals, G., Roos-Hesselink, J.W., Graaf, B.M. de, Verhagen, J.M., Hoedemaekers, Y.M., Willemsen, R., Severijnen, L.A., Venselaar, H., Vriend, G., Pattynama, P.M., Collee, M., Majoor-Krakauer, D., Poldermans, D., Frohn-Mulder, I.M., Micha, D., Timmermans, J., Hilhorst-Hofstee, Y., Bierma-Zeinstra, S.M., Willems, P.J., Kros, J.M., Oei, E.H., Oostra, B.A., Wessels, M.W., Bertoli-Avella, A.M., Laar, I.M. van de, Oldenburg, R.A., Pals, G., Roos-Hesselink, J.W., Graaf, B.M. de, Verhagen, J.M., Hoedemaekers, Y.M., Willemsen, R., Severijnen, L.A., Venselaar, H., Vriend, G., Pattynama, P.M., Collee, M., Majoor-Krakauer, D., Poldermans, D., Frohn-Mulder, I.M., Micha, D., Timmermans, J., Hilhorst-Hofstee, Y., Bierma-Zeinstra, S.M., Willems, P.J., Kros, J.M., Oei, E.H., Oostra, B.A., Wessels, M.W., and Bertoli-Avella, A.M.

Abstract

Contains fulltext : 92104.pdf (publisher's version ) (Closed access)

Published
2011

17. P4-11-04: Risk of Primary (PBC) and Contralateral Breast Cancer (CBC) after Ovarian Cancer (OC) in BRCA1 and BRCA2 Mutation Carriers; Implications for Surveillance and Risk Reducing Mastectomy.

Author

Seynaeve, C, primary, Vencken, P, additional, Hooning, M, additional, Menke-Pluymers, M, additional, Heemskerk-Gerritsen, A, additional, Van, Doorn L, additional, Collee, M, additional, Jager, A, additional, Van, Montfort K, additional, Burger, C, additional, and Kriege, M, additional

Published
2011
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20. Contralateral Breast Cancer in BRCA1/2 Mutation Carriers: Risk Assessment by Age at Diagnosis of the First Primary Breast Cancer.

Author

Hooning, M., primary, Heemskerk-Gerritsen, B., additional, Jager, A., additional, Collee, M., additional, van den Ouweland, A., additional, Menke - Pluymers, M., additional, van Geel, B., additional, van Doorn, L., additional, Tilanus - Linthorst, M., additional, Bartels, C., additional, and Seynaeve, C., additional

Published
2009
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22. Cardiovascular disease risk after breast cancer treatment in patients with a BRCA1/2 pathogenic variant.

Author

Terra L, Boekel NB, Hooning MH, Collee M, Schmidt MK, Adank MA, Kok M, Aleman BMP, Jager A, Sattler MGA, Maas AHEM, Schaapveld M, and van Leeuwen FE

Subjects
Humans, Female, Middle Aged, Adult, Aged, Genetic Predisposition to Disease, Risk Factors, Heterozygote, Follow-Up Studies, Breast Neoplasms genetics, Breast Neoplasms therapy, BRCA1 Protein genetics, BRCA2 Protein genetics, Cardiovascular Diseases etiology, Cardiovascular Diseases genetics, Cardiovascular Diseases epidemiology
Abstract

Purpose: Breast cancer (BC) treatment can induce adverse events, such as cardiovascular disease (CVD). Defective DNA repair, as in carriers of BRCA1/2 pathogenic variants (BRCA1/2pv), may contribute to CVD risk. We aimed to study if female BRCA1/2pv carriers are more sensitive to develop CVD after BC treatment than BC patients without a known BRCA1/2pv., Methods: In a hospital-based cohort of 17,300 female BC patients, we identified 509 BRCA1/2pv carriers. Cardiovascular morbidity and mortality were assessed through hospital charts and general practitioner questionnaires. We performed Cox regression analyses comparing BRCA1/2pv carriers with all other BC patients, adjusting for age, radiotherapy regimen, chemotherapy regimen, and smoking status., Results: Median follow-up time since BC treatment was 14 years. In total, 1108 women experienced ischemic heart disease (IHD), of whom 20 (1.8%) were BRCA1/2pv carriers. Heart failure (HF) was diagnosed in 638 women, of whom 10 (1.6%) were BRCA1/2pv carriers. BRCA1/2pv carriership was associated with a slight not statistically significant increase of IHD (adjHR 1.51, 95%CI 0.93; 2.42), but not with risk of HF (adjHR 0.86, 95%CI 0.44; 1.69). The association between radiotherapy and IHD risk was not significantly different between BRCA1/2pv carriers [HR 2.30 (95%CI 0.79; 6.66)] and other BC patients (HR 1.50, 95%CI 1.30; 1.73). Associations between anthracycline-based chemotherapy and HF risk also did not differ between carriers and other BC patients (HRs of 4.02 (95%CI 1.02; 15.77) and 2.31 (95%CI 1.77; 3.01), respectively)., Conclusions: In BRCA1/2pv BC patients, we found no evidence for a higher risk of BC treatment-related CVD than in other BC patients., Competing Interests: Declarations. Conflict of interest: M Kok: Receives funding paid to the institute from BMS, Roche, AstraZeneca and Daiicho Sankyo. Advisory roles for: Daiichi Sankyo, BMS, MSD, Roche. Speakers’ fee from: Roche, BMS and Gilead. All outside the submitted work., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2025
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23. Phenomena of hypo- and hyperconnectivity in basal ganglia-thalamo-cortical circuits linked to major depression: a 7T fMRI study.

Author

Hagen J, Ramkiran S, Schnellbächer GJ, Rajkumar R, Collee M, Khudeish N, Veselinović T, Shah NJ, and Neuner I

Subjects
Humans, Female, Male, Adult, Middle Aged, Cerebral Cortex physiopathology, Brain Mapping methods, Connectome methods, Case-Control Studies, Depressive Disorder, Major physiopathology, Magnetic Resonance Imaging methods, Basal Ganglia physiopathology, Thalamus physiopathology, Neural Pathways physiopathology, Nerve Net physiopathology, Nerve Net diagnostic imaging
Abstract

Major depressive disorder (MDD) typically manifests itself in depressed affect, anhedonia, low energy, and additional symptoms. Despite its high global prevalence, its pathophysiology still gives rise to questions. Current research places alterations in functional connectivity among MDD's most promising biomarkers. However, given the heterogeneity of previous findings, the use of higher-resolution imaging techniques, like ultra-high field (UHF) fMRI (≥7 Tesla, 7T), may offer greater specificity in delineating fundamental impairments. In this study, 7T UHF fMRI scans were conducted on 31 MDD patients and 27 age-gender matched healthy controls to exploratorily contrast cerebral resting-state functional connectivity patterns between both groups. The CONN toolbox was used to generate functional network connectivity (FNC) analysis based on the region of interest (ROI)-to-ROI correlations in order to enable the identification of clusters of significantly different connections. Correction for multiple comparisons was implemented at the cluster level using a false discovery rate (FDR). The analysis revealed three significant clusters differentiating MDD patients and healthy controls. In Clusters 1 and 2, MDD patients exhibited between-network hypoconnectivity in basal ganglia-cortical pathways as well as hyperconnectivity in thalamo-cortical pathways, including several individual ROI-to-ROI connections. In Cluster 3, they showed increased occipital interhemispheric within-network connectivity. These findings suggest that alterations in basal ganglia-thalamo-cortical circuits play a substantial role in the pathophysiology of MDD. Furthermore, they indicate potential MDD-related deficits relating to a combination of perception (vision, audition, and somatosensation) as well as more complex functions, especially social-emotional processing, modulation, and regulation. It is anticipated that these findings might further inform more accurate clinical procedures for addressing MDD., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Published
2025
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24. Structural alterations as a predictor of depression - a 7-Tesla MRI-based multidimensional approach.

Author

Schnellbächer GJ, Rajkumar R, Veselinović T, Ramkiran S, Hagen J, Collee M, Shah NJ, and Neuner I

Abstract

Major depressive disorder (MDD) is a debilitating condition that is associated with changes in the default-mode network (DMN). Commonly reported features include alterations in gray matter volume (GMV), cortical thickness (CoT), and gyrification. A comprehensive examination of these variables using ultra-high field strength MRI and machine learning methods may lead to novel insights into the pathophysiology of depression and help develop a more personalized therapy. Cerebral images were obtained from 41 patients with confirmed MDD and 41 healthy controls, matched for age and gender, using a 7-T-MRI. DMN parcellation followed the Schaefer 600 Atlas. Based on the results of a mixed-model repeated measures analysis, a support vector machine (SVM) calculation followed by leave-one-out cross-validation determined the predictive ability of structural features for the presence of MDD. A consecutive permutation procedure identified which areas contributed to the classification results. Correlating changes in those areas with BDI-II and AMDP scores added an explanatory aspect to this study. CoT did not delineate relevant changes in the mixed model and was excluded from further analysis. The SVM achieved a good prediction accuracy of 0.76 using gyrification data. GMV was not a viable predictor for disease presence, however, it correlated in the left parahippocampal gyrus with disease severity as measured by the BDI-II. Structural data of the DMN may therefore contain the necessary information to predict the presence of MDD. However, there may be inherent challenges with predicting disease course or treatment response due to high GMV variance and the static character of gyrification. Further improvements in data acquisition and analysis may help to overcome these difficulties., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Published
2024
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25. Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer: Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study).

Author

Terra L, Hooning MJ, Heemskerk-Gerritsen BAM, van Beurden M, Roeters van Lennep JE, van Doorn HC, de Hullu JA, Mom C, van Dorst EBL, Mourits MJE, Slangen BFM, Gaarenstroom KN, Zillikens MC, Leiner T, van der Kolk L, Collee M, Wevers M, Ausems MGEM, van Engelen K, Berger LP, van Asperen CJ, Gomez-Garcia EB, van de Beek I, Rookus MA, Hauptmann M, Bleiker EM, Schagen SB, Aaronson NK, Maas AHEM, and van Leeuwen FE

Abstract

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited., Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer., Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery., Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study., Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO., Trial Registration: ClinicalTrials.gov NCT03835793; https://clinicaltrials.gov/ct2/show/NCT03835793., International Registered Report Identifier (irrid): DERR1-10.2196/24414., (©Lara Terra, Maartje J Hooning, Bernadette A M Heemskerk-Gerritsen, Marc van Beurden, Jeanine E Roeters van Lennep, Helena C van Doorn, Joanne A de Hullu, Constantijne Mom, Eleonora B L van Dorst, Marian J E Mourits, Brigitte F M Slangen, Katja N Gaarenstroom, M Carola Zillikens, Tim Leiner, Lizet van der Kolk, Margriet Collee, Marijke Wevers, Margreet G E M Ausems, Klaartje van Engelen, Lieke PV Berger, Christi J van Asperen, Encarna B Gomez-Garcia, Irma van de Beek, Matti A Rookus, Michael Hauptmann, Eveline M Bleiker, Sanne B Schagen, Neil K Aaronson, Angela H E M Maas, Flora E van Leeuwen. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.01.2021.)

Published
2021
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