Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Paolo Peterlongo; Jenny Chang-Claude; Kirsten B Moysich; Anja Rudolph; Rita K Schmutzler; Jacques Simard; Penny Soucy; Rosalind A Eeles; Douglas F Easton; Ute Hamann; Stefan Wilkening; Bowang Chen; Matti A Rookus; Marjanka K Schmidt; Frederieke H van der Baan; Amanda B Spurdle; Logan C Walker; Felicity Lose; Ana-Teresa Maia; Marco Montagna; Laura Matricardi; Jan Lubinski; Anna Jakubowska; Encarna B Gómez Garcia; Olufunmilayo I Olopade; Robert L Nussbaum; Katherine L Nathanson; Susan M Domchek; Timothy R Rebbeck; Banu K Arun; Beth Y Karlan; Sandra Orsulic; Jenny Lester; Wendy K Chung; Alex Miron; Melissa C Southey; David E Goldgar; Saundra S Buys; Ramunas Janavicius; Cecilia M Dorfling; Elizabeth J van Rensburg; Yuan Chun Ding; Susan L Neuhausen; Thomas V O Hansen; Anne-Marie Gerdes; Bent Ejlertsen; Lars Jønson; Ana Osorio; Cristina Martínez-Bouzas; Javier Benitez; Edye E Conway; Kathleen R Blazer; Jeffrey N Weitzel; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Giulietta Scuvera; Monica Barile; Filomena Ficarazzi; Frederique Mariette; Stefano Fortuzzi; Alessandra Viel; Giuseppe Giannini; Laura Papi; Aline Martayan; Maria Grazia Tibiletti; Paolo Radice; Athanassios Vratimos; Florentia Fostira; Judy E Garber; Alan Donaldson; Carole Brewer; Claire Foo; D Gareth R Evans; Debra Frost; Diana Eccles; Angela Brady; Jackie Cook; Marc Tischkowitz; Julian Adlard; Julian Barwell; Lisa Walker; Louise Izatt; Lucy E Side; M John Kennedy; Mark T Rogers; Mary E Porteous; Patrick J Morrison; Radka Platte; Rosemarie Davidson; Shirley V Hodgson; Steve Ellis; Trevor Cole; Andrew K Godwin; Kathleen Claes; Tom Van Maerken; Alfons Meindl; Andrea Gehrig; Christian Sutter; Christoph Engel; Dieter Niederacher; Doris Steinemann; Hansjoerg Plendl; Karin Kast; Kerstin Rhiem; Nina Ditsch; Norbert Arnold; Raymonda Varon-Mateeva; Barbara Wappenschmidt; Shan Wang-Gohrke; Brigitte Bressac-de Paillerets; Bruno Buecher; Capucine Delnatte; Claude Houdayer; Dominique Stoppa-Lyonnet; Francesca Damiola; Isabelle Coupier; Laure Barjhoux; Laurence Venat-Bouvet; Lisa Golmard; Nadia Boutry-Kryza; Olga M Sinilnikova; Olivier Caron; Pascal Pujol; Sylvie Mazoyer; Muriel Belotti; Marion Piedmonte; Michael L Friedlander; Gustavo C Rodriguez; Larry J Copeland; Miguel de la Hoya; Pedro Perez Segura; Heli Nevanlinna; Kristiina Aittomäki; Theo A M van Os; Hanne E J Meijers-Heijboer; Annemarie H van der Hout; Maaike P G Vreeswijk; Nicoline Hoogerbrugge; Margreet G E M Ausems; Helena C van Doorn; J Margriet Collée; Edith Olah; Orland Diez; Ignacio Blanco; Conxi Lazaro; Joan Brunet; Lidia Feliubadalo; Cezary Cybulski; Jacek Gronwald; Katarzyna Durda; Katarzyna Jaworska-Bieniek; Grzegorz Sukiennicki; Adalgeir Arason; Jocelyne Chiquette; Manuel R Teixeira; Curtis Olswold; Fergus J Couch; Noralane M Lindor; Xianshu Wang; Csilla I Szabo; Kenneth Offit; Marina Corines; Lauren Jacobs; Mark E Robson; Liying Zhang; Vijai Joseph; Andreas Berger; Christian F Singer; Christine Rappaport; Daphne Geschwantler Kaulich; Georg Pfeiler; Muy-Kheng M Tea; Catherine M Phelan; Mark H Greene; Phuong L Mai; Gad Rennert; Anna Marie Mulligan; Gord Glendon; Sandrine Tchatchou; Irene L Andrulis; Amanda Ewart Toland; Anders Bojesen; Inge Sokilde Pedersen; Mads Thomassen; Uffe Birk Jensen; Yael Laitman; Johanna Rantala; Anna von Wachenfeldt; Hans Ehrencrona; Marie Stenmark Askmalm; Åke Borg; Karoline B Kuchenbaecker; Lesley McGuffog; Daniel Barrowdale; Sue Healey; Andrew Lee; Paul D P Pharoah; Georgia Chenevix-Trench; Antonis C Antoniou; Eitan Friedman; Cecelia M Dorfling; Ake Borg

doi:10.1158/1055-9965.EPI-14-0532

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Paolo Peterlongo, Jenny Chang-Claude, Kirsten B Moysich, Anja Rudolph, Rita K Schmutzler, Jacques Simard, Penny Soucy, Rosalind A Eeles, Douglas F Easton, Ute Hamann, Stefan Wilkening, Bowang Chen, Matti A Rookus, Marjanka K Schmidt, Frederieke H van der Baan, Amanda B Spurdle, Logan C Walker, Felicity Lose, Ana-Teresa Maia, Marco MontagnaLaura Matricardi, Jan Lubinski, Anna Jakubowska, Encarna B Gómez Garcia, Olufunmilayo I Olopade, Robert L Nussbaum, Katherine L Nathanson, Susan M Domchek, Timothy R Rebbeck, Banu K Arun, Beth Y Karlan, Sandra Orsulic, Jenny Lester, Wendy K Chung, Alex Miron, Melissa C Southey, David E Goldgar, Saundra S Buys, Ramunas Janavicius, Cecilia M Dorfling, Elizabeth J van Rensburg, Yuan Chun Ding, Susan L Neuhausen, Thomas V O Hansen, Anne-Marie Gerdes, Bent Ejlertsen, Lars Jønson, Ana Osorio, Cristina Martínez-Bouzas, Javier Benitez, Edye E Conway, Kathleen R Blazer, Jeffrey N Weitzel, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Giulietta Scuvera, Monica Barile, Filomena Ficarazzi, Frederique Mariette, Stefano Fortuzzi, Alessandra Viel, Giuseppe Giannini, Laura Papi, Aline Martayan, Maria Grazia Tibiletti, Paolo Radice, Athanassios Vratimos, Florentia Fostira, Judy E Garber, Alan Donaldson, Carole Brewer, Claire Foo, D Gareth R Evans, Debra Frost, Diana Eccles, Angela Brady, Jackie Cook, Marc Tischkowitz, Julian Adlard, Julian Barwell, Lisa Walker, Louise Izatt, Lucy E Side, M John Kennedy, Mark T Rogers, Mary E Porteous, Patrick J Morrison, Radka Platte, Rosemarie Davidson, Shirley V Hodgson, Steve Ellis, Trevor Cole, Andrew K Godwin, Kathleen Claes, Tom Van Maerken, Alfons Meindl, Andrea Gehrig, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Hansjoerg Plendl, Karin Kast, Kerstin Rhiem, Nina Ditsch, Norbert Arnold, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Shan Wang-Gohrke, Brigitte Bressac-de Paillerets, Bruno Buecher, Capucine Delnatte, Claude Houdayer, Dominique Stoppa-Lyonnet, Francesca Damiola, Isabelle Coupier, Laure Barjhoux, Laurence Venat-Bouvet, Lisa Golmard, Nadia Boutry-Kryza, Olga M Sinilnikova, Olivier Caron, Pascal Pujol, Sylvie Mazoyer, Muriel Belotti, Marion Piedmonte, Michael L Friedlander, Gustavo C Rodriguez, Larry J Copeland, Miguel de la Hoya, Pedro Perez Segura, Heli Nevanlinna, Kristiina Aittomäki, Theo A M van Os, Hanne E J Meijers-Heijboer, Annemarie H van der Hout, Maaike P G Vreeswijk, Nicoline Hoogerbrugge, Margreet G E M Ausems, Helena C van Doorn, J Margriet Collée, Edith Olah, Orland Diez, Ignacio Blanco, Conxi Lazaro, Joan Brunet, Lidia Feliubadalo, Cezary Cybulski, Jacek Gronwald, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Grzegorz Sukiennicki, Adalgeir Arason, Jocelyne Chiquette, Manuel R Teixeira, Curtis Olswold, Fergus J Couch, Noralane M Lindor, Xianshu Wang, Csilla I Szabo, Kenneth Offit, Marina Corines, Lauren Jacobs, Mark E Robson, Liying Zhang, Vijai Joseph, Andreas Berger, Christian F Singer, Christine Rappaport, Daphne Geschwantler Kaulich, Georg Pfeiler, Muy-Kheng M Tea, Catherine M Phelan, Mark H Greene, Phuong L Mai, Gad Rennert, Anna Marie Mulligan, Gord Glendon, Sandrine Tchatchou, Irene L Andrulis, Amanda Ewart Toland, Anders Bojesen, Inge Sokilde Pedersen, Mads Thomassen, Uffe Birk Jensen, Yael Laitman, Johanna Rantala, Anna von Wachenfeldt, Hans Ehrencrona, Marie Stenmark Askmalm, Åke Borg, Karoline B Kuchenbaecker, Lesley McGuffog, Daniel Barrowdale, Sue Healey, Andrew Lee, Paul D P Pharoah, Georgia Chenevix-Trench, Antonis C Antoniou, Eitan Friedman, Cecelia M Dorfling, Ake Borg

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

Original language	English
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume	24
Issue number	1
DOIs	https://doi.org/10.1158/1055-9965.EPI-14-0532
Publication status	Published - Jan 2015

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10.1158/1055-9965.EPI-14-0532

Cite this

Peterlongo, P., Chang-Claude, J., Moysich, K. B., Rudolph, A., Schmutzler, R. K., Simard, J., Soucy, P., Eeles, R. A., Easton, D. F., Hamann, U., Wilkening, S., Chen, B., Rookus, M. A., Schmidt, M. K., van der Baan, F. H., Spurdle, A. B., Walker, L. C., Lose, F., Maia, A.-T., ... Borg, A. (2015). Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 24(1). https://doi.org/10.1158/1055-9965.EPI-14-0532

@article{d9b2bccdb6894d2197d58a86c4921ca3,

title = "Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.",

abstract = "BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.",

author = "Paolo Peterlongo and Jenny Chang-Claude and Moysich, {Kirsten B} and Anja Rudolph and Schmutzler, {Rita K} and Jacques Simard and Penny Soucy and Eeles, {Rosalind A} and Easton, {Douglas F} and Ute Hamann and Stefan Wilkening and Bowang Chen and Rookus, {Matti A} and Schmidt, {Marjanka K} and {van der Baan}, {Frederieke H} and Spurdle, {Amanda B} and Walker, {Logan C} and Felicity Lose and Ana-Teresa Maia and Marco Montagna and Laura Matricardi and Jan Lubinski and Anna Jakubowska and {G{\'o}mez Garcia}, {Encarna B} and Olopade, {Olufunmilayo I} and Nussbaum, {Robert L} and Nathanson, {Katherine L} and Domchek, {Susan M} and Rebbeck, {Timothy R} and Arun, {Banu K} and Karlan, {Beth Y} and Sandra Orsulic and Jenny Lester and Chung, {Wendy K} and Alex Miron and Southey, {Melissa C} and Goldgar, {David E} and Buys, {Saundra S} and Ramunas Janavicius and Dorfling, {Cecilia M} and {van Rensburg}, {Elizabeth J} and Ding, {Yuan Chun} and Neuhausen, {Susan L} and Hansen, {Thomas V O} and Anne-Marie Gerdes and Bent Ejlertsen and Lars J{\o}nson and Ana Osorio and Cristina Mart{\'i}nez-Bouzas and Javier Benitez and Conway, {Edye E} and Blazer, {Kathleen R} and Weitzel, {Jeffrey N} and Siranoush Manoukian and Bernard Peissel and Daniela Zaffaroni and Giulietta Scuvera and Monica Barile and Filomena Ficarazzi and Frederique Mariette and Stefano Fortuzzi and Alessandra Viel and Giuseppe Giannini and Laura Papi and Aline Martayan and Tibiletti, {Maria Grazia} and Paolo Radice and Athanassios Vratimos and Florentia Fostira and Garber, {Judy E} and Alan Donaldson and Carole Brewer and Claire Foo and Evans, {D Gareth R} and Debra Frost and Diana Eccles and Angela Brady and Jackie Cook and Marc Tischkowitz and Julian Adlard and Julian Barwell and Lisa Walker and Louise Izatt and Side, {Lucy E} and Kennedy, {M John} and Rogers, {Mark T} and Porteous, {Mary E} and Morrison, {Patrick J} and Radka Platte and Rosemarie Davidson and Hodgson, {Shirley V} and Steve Ellis and Trevor Cole and Godwin, {Andrew K} and Kathleen Claes and {Van Maerken}, Tom and Alfons Meindl and Andrea Gehrig and Christian Sutter and Christoph Engel and Dieter Niederacher and Doris Steinemann and Hansjoerg Plendl and Karin Kast and Kerstin Rhiem and Nina Ditsch and Norbert Arnold and Raymonda Varon-Mateeva and Barbara Wappenschmidt and Shan Wang-Gohrke and {Bressac-de Paillerets}, Brigitte and Bruno Buecher and Capucine Delnatte and Claude Houdayer and Dominique Stoppa-Lyonnet and Francesca Damiola and Isabelle Coupier and Laure Barjhoux and Laurence Venat-Bouvet and Lisa Golmard and Nadia Boutry-Kryza and Sinilnikova, {Olga M} and Olivier Caron and Pascal Pujol and Sylvie Mazoyer and Muriel Belotti and Marion Piedmonte and Friedlander, {Michael L} and Rodriguez, {Gustavo C} and Copeland, {Larry J} and {de la Hoya}, Miguel and Segura, {Pedro Perez} and Heli Nevanlinna and Kristiina Aittom{\"a}ki and {van Os}, {Theo A M} and Meijers-Heijboer, {Hanne E J} and {van der Hout}, {Annemarie H} and Vreeswijk, {Maaike P G} and Nicoline Hoogerbrugge and Ausems, {Margreet G E M} and {van Doorn}, {Helena C} and Coll{\'e}e, {J Margriet} and Edith Olah and Orland Diez and Ignacio Blanco and Conxi Lazaro and Joan Brunet and Lidia Feliubadalo and Cezary Cybulski and Jacek Gronwald and Katarzyna Durda and Katarzyna Jaworska-Bieniek and Grzegorz Sukiennicki and Adalgeir Arason and Jocelyne Chiquette and Teixeira, {Manuel R} and Curtis Olswold and Couch, {Fergus J} and Lindor, {Noralane M} and Xianshu Wang and Szabo, {Csilla I} and Kenneth Offit and Marina Corines and Lauren Jacobs and Robson, {Mark E} and Liying Zhang and Vijai Joseph and Andreas Berger and Singer, {Christian F} and Christine Rappaport and Kaulich, {Daphne Geschwantler} and Georg Pfeiler and Tea, {Muy-Kheng M} and Phelan, {Catherine M} and Greene, {Mark H} and Mai, {Phuong L} and Gad Rennert and Mulligan, {Anna Marie} and Gord Glendon and Sandrine Tchatchou and Andrulis, {Irene L} and Toland, {Amanda Ewart} and Anders Bojesen and Pedersen, {Inge Sokilde} and Mads Thomassen and Jensen, {Uffe Birk} and Yael Laitman and Johanna Rantala and {von Wachenfeldt}, Anna and Hans Ehrencrona and Askmalm, {Marie Stenmark} and {\AA}ke Borg and Kuchenbaecker, {Karoline B} and Lesley McGuffog and Daniel Barrowdale and Sue Healey and Andrew Lee and Pharoah, {Paul D P} and Georgia Chenevix-Trench and Antoniou, {Antonis C} and Eitan Friedman and Dorfling, {Cecelia M} and Ake Borg",

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year = "2015",

month = jan,

doi = "10.1158/1055-9965.EPI-14-0532",

language = "English",

volume = "24",

journal = "Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology",

issn = "1538-7755",

publisher = "American Association for Cancer Research",

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}

Peterlongo, P, Chang-Claude, J, Moysich, KB, Rudolph, A, Schmutzler, RK, Simard, J, Soucy, P, Eeles, RA, Easton, DF, Hamann, U, Wilkening, S, Chen, B, Rookus, MA, Schmidt, MK, van der Baan, FH, Spurdle, AB, Walker, LC, Lose, F, Maia, A-T, Montagna, M, Matricardi, L, Lubinski, J, Jakubowska, A, Gómez Garcia, EB, Olopade, OI, Nussbaum, RL, Nathanson, KL, Domchek, SM, Rebbeck, TR, Arun, BK, Karlan, BY, Orsulic, S, Lester, J, Chung, WK, Miron, A, Southey, MC, Goldgar, DE, Buys, SS, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Ding, YC, Neuhausen, SL, Hansen, TVO, Gerdes, A-M, Ejlertsen, B, Jønson, L, Osorio, A, Martínez-Bouzas, C, Benitez, J, Conway, EE, Blazer, KR, Weitzel, JN, Manoukian, S, Peissel, B, Zaffaroni, D, Scuvera, G, Barile, M, Ficarazzi, F, Mariette, F, Fortuzzi, S, Viel, A, Giannini, G, Papi, L, Martayan, A, Tibiletti, MG, Radice, P, Vratimos, A, Fostira, F, Garber, JE, Donaldson, A, Brewer, C, Foo, C, Evans, DGR, Frost, D, Eccles, D, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Davidson, R, Hodgson, SV, Ellis, S, Cole, T, Godwin, AK, Claes, K, Van Maerken, T, Meindl, A, Gehrig, A, Sutter, C, Engel, C, Niederacher, D, Steinemann, D, Plendl, H, Kast, K, Rhiem, K, Ditsch, N, Arnold, N, Varon-Mateeva, R, Wappenschmidt, B, Wang-Gohrke, S, Bressac-de Paillerets, B, Buecher, B, Delnatte, C, Houdayer, C, Stoppa-Lyonnet, D, Damiola, F, Coupier, I, Barjhoux, L, Venat-Bouvet, L, Golmard, L, Boutry-Kryza, N, Sinilnikova, OM, Caron, O, Pujol, P, Mazoyer, S, Belotti, M, Piedmonte, M, Friedlander, ML, Rodriguez, GC, Copeland, LJ, de la Hoya, M, Segura, PP, Nevanlinna, H, Aittomäki, K, van Os, TAM, Meijers-Heijboer, HEJ, van der Hout, AH, Vreeswijk, MPG, Hoogerbrugge, N, Ausems, MGEM, van Doorn, HC, Collée, JM, Olah, E, Diez, O, Blanco, I, Lazaro, C, Brunet, J, Feliubadalo, L, Cybulski, C, Gronwald, J, Durda, K, Jaworska-Bieniek, K, Sukiennicki, G, Arason, A, Chiquette, J, Teixeira, MR, Olswold, C, Couch, FJ, Lindor, NM, Wang, X, Szabo, CI, Offit, K, Corines, M, Jacobs, L, Robson, ME, Zhang, L, Joseph, V, Berger, A, Singer, CF, Rappaport, C, Kaulich, DG, Pfeiler, G, Tea, M-KM, Phelan, CM, Greene, MH, Mai, PL, Rennert, G, Mulligan, AM, Glendon, G, Tchatchou, S, Andrulis, IL, Toland, AE, Bojesen, A, Pedersen, IS, Thomassen, M, Jensen, UB, Laitman, Y, Rantala, J, von Wachenfeldt, A, Ehrencrona, H, Askmalm, MS, Borg, Å, Kuchenbaecker, KB, McGuffog, L, Barrowdale, D, Healey, S, Lee, A, Pharoah, PDP, Chenevix-Trench, G, Antoniou, AC, Friedman, E, Dorfling, CM & Borg, A 2015, 'Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.', Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol. 24, no. 1. https://doi.org/10.1158/1055-9965.EPI-14-0532

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. / Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B et al.
In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Vol. 24, No. 1, 01.2015.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

AU - Peterlongo, Paolo

AU - Chang-Claude, Jenny

AU - Moysich, Kirsten B

AU - Rudolph, Anja

AU - Schmutzler, Rita K

AU - Simard, Jacques

AU - Soucy, Penny

AU - Eeles, Rosalind A

AU - Easton, Douglas F

AU - Hamann, Ute

AU - Wilkening, Stefan

AU - Chen, Bowang

AU - Rookus, Matti A

AU - Schmidt, Marjanka K

AU - van der Baan, Frederieke H

AU - Spurdle, Amanda B

AU - Walker, Logan C

AU - Lose, Felicity

AU - Maia, Ana-Teresa

AU - Montagna, Marco

AU - Matricardi, Laura

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Gómez Garcia, Encarna B

AU - Olopade, Olufunmilayo I

AU - Nussbaum, Robert L

AU - Nathanson, Katherine L

AU - Domchek, Susan M

AU - Rebbeck, Timothy R

AU - Arun, Banu K

AU - Karlan, Beth Y

AU - Orsulic, Sandra

AU - Lester, Jenny

AU - Chung, Wendy K

AU - Miron, Alex

AU - Southey, Melissa C

AU - Goldgar, David E

AU - Buys, Saundra S

AU - Janavicius, Ramunas

AU - Dorfling, Cecilia M

AU - van Rensburg, Elizabeth J

AU - Ding, Yuan Chun

AU - Neuhausen, Susan L

AU - Hansen, Thomas V O

AU - Gerdes, Anne-Marie

AU - Ejlertsen, Bent

AU - Jønson, Lars

AU - Osorio, Ana

AU - Martínez-Bouzas, Cristina

AU - Benitez, Javier

AU - Conway, Edye E

AU - Blazer, Kathleen R

AU - Weitzel, Jeffrey N

AU - Manoukian, Siranoush

AU - Peissel, Bernard

AU - Zaffaroni, Daniela

AU - Scuvera, Giulietta

AU - Barile, Monica

AU - Ficarazzi, Filomena

AU - Mariette, Frederique

AU - Fortuzzi, Stefano

AU - Viel, Alessandra

AU - Giannini, Giuseppe

AU - Papi, Laura

AU - Martayan, Aline

AU - Tibiletti, Maria Grazia

AU - Radice, Paolo

AU - Vratimos, Athanassios

AU - Fostira, Florentia

AU - Garber, Judy E

AU - Donaldson, Alan

AU - Brewer, Carole

AU - Foo, Claire

AU - Evans, D Gareth R

AU - Frost, Debra

AU - Eccles, Diana

AU - Brady, Angela

AU - Cook, Jackie

AU - Tischkowitz, Marc

AU - Adlard, Julian

AU - Barwell, Julian

AU - Walker, Lisa

AU - Izatt, Louise

AU - Side, Lucy E

AU - Kennedy, M John

AU - Rogers, Mark T

AU - Porteous, Mary E

AU - Morrison, Patrick J

AU - Platte, Radka

AU - Davidson, Rosemarie

AU - Hodgson, Shirley V

AU - Ellis, Steve

AU - Cole, Trevor

AU - Godwin, Andrew K

AU - Claes, Kathleen

AU - Van Maerken, Tom

AU - Meindl, Alfons

AU - Gehrig, Andrea

AU - Sutter, Christian

AU - Engel, Christoph

AU - Niederacher, Dieter

AU - Steinemann, Doris

AU - Plendl, Hansjoerg

AU - Kast, Karin

AU - Rhiem, Kerstin

AU - Ditsch, Nina

AU - Arnold, Norbert

AU - Varon-Mateeva, Raymonda

AU - Wappenschmidt, Barbara

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N1 - 10119, Cancer Research UK, United Kingdom10124, Cancer Research UK, United Kingdom1R01 CA149429-01, NCI NIH HHS, United States1U19 CA148065, NCI NIH HHS, United States1U19 CA148112, NCI NIH HHS, United States1U19CA148537, NCI NIH HHS, United States5U01CA113916, NCI NIH HHS, United StatesA10118, Cancer Research UK, United KingdomA10692, Cancer Research UK, United KingdomA10710, Cancer Research UK, United KingdomA11174, Cancer Research UK, United KingdomA12014, Cancer Research UK, United KingdomA15007, Cancer Research UK, United KingdomA16563, Cancer Research UK, United KingdomA17523, Cancer Research UK, United KingdomA8385, Cancer Research UK, United KingdomC12292/A11174, Cancer Research UK, United KingdomC1281/A12014, Cancer Research UK, United KingdomC1287/A 10710, Cancer Research UK, United KingdomC1287/A10118, Cancer Research UK, United KingdomC1287/A16563, Cancer Research UK, United KingdomC1287/A17523, Cancer Research UK, United KingdomC5047/A10692, Cancer Research UK, United KingdomC5047/A15007, Cancer Research UK, United KingdomC5047/A8384, Cancer Research UK, United KingdomC5047/A8385, Cancer Research UK, United KingdomCA 27469, NCI NIH HHS, United StatesCA116201, NCI NIH HHS, United StatesCA128978, NCI NIH HHS, United StatesM01 RR000043, NCRR NIH HHS, United StatesP30 CA015083, NCI NIH HHS, United StatesP30 CA168524, NCI NIH HHS, United StatesP30 CA168524, NCI NIH HHS, United StatesP50 CA159981, NCI NIH HHS, United StatesR01 CA126841, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01 CA140323, NCI NIH HHS, United StatesR01-CA083855, NCI NIH HHS, United StatesR01-CA102776, NCI NIH HHS, United StatesR01CA140323, NCI NIH HHS, United StatesRC4 CA153828, NCI NIH HHS, United StatesRC4CA153828, NCI NIH HHS, United StatesU10 CA027469, NCI NIH HHS, United StatesU10 CA037517, NCI NIH HHS, United StatesU10 CA180822, NCI NIH HHS, United StatesU10 CA180868, NCI NIH HHS, United StatesUL1 TR000430, NCATS NIH HHS, United StatesUM1 CA164920, NCI NIH HHS, United States, Canadian Institutes of Health Research, Canada

PY - 2015/1

Y1 - 2015/1

N2 - BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

AB - BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. RESULTS: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. CONCLUSION: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. IMPACT: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

U2 - 10.1158/1055-9965.EPI-14-0532

DO - 10.1158/1055-9965.EPI-14-0532

M3 - Article

C2 - 25336561

SN - 1538-7755

VL - 24

JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

IS - 1

ER -

Peterlongo P, Chang-Claude J, Moysich KB, Rudolph A, Schmutzler RK, Simard J et al. Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2015 Jan;24(1). doi: 10.1158/1055-9965.EPI-14-0532

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

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