Prediction of breast cancer risk based on profiling with common genetic variants

Nasim Mavaddat; Paul D P Pharoah; Kyriaki Michailidou; Jonathan Tyrer; Mark N Brook; Manjeet K Bolla; Qin Wang; Joe Dennis; Alison M Dunning; Mitul Shah; Robert Luben; Judith Brown; Stig E Bojesen; Børge G Nordestgaard; Sune F Nielsen; Henrik Flyger; Kamila Czene; Hatef Darabi; Mikael Eriksson; Julian Peto; Isabel Dos-Santos-Silva; Frank Dudbridge; Nichola Johnson; Marjanka K Schmidt; Annegien Broeks; Senno Verhoef; Emiel J Rutgers; Anthony Swerdlow; Alan Ashworth; Nick Orr; Minouk J Schoemaker; Jonine Figueroa; Stephen J Chanock; Louise Brinton; Jolanta Lissowska; Fergus J Couch; Janet E Olson; Celine Vachon; Vernon S Pankratz; Diether Lambrechts; Hans Wildiers; Chantal Van Ongeval; Erik van Limbergen; Vessela Kristensen; Grethe Grenaker Alnæs; Silje Nord; Anne-Lise Borresen-Dale; Heli Nevanlinna; Taru A Muranen; Kristiina Aittomäki; Carl Blomqvist; Jenny Chang-Claude; Anja Rudolph; Petra Seibold; Dieter Flesch-Janys; Peter A Fasching; Lothar Haeberle; Arif B Ekici; Matthias W Beckmann; Barbara Burwinkel; Frederik Marme; Andreas Schneeweiss; Christof Sohn; Amy Trentham-Dietz; Polly Newcomb; Linda Titus; Kathleen M Egan; David J Hunter; Sara Lindstrom; Rulla M Tamimi; Peter Kraft; Nazneen Rahman; Clare Turnbull; Anthony Renwick; Sheila Seal; Jingmei Li; Jianjun Liu; Keith Humphreys; Javier Benitez; M Pilar Zamora; Jose Ignacio Arias Perez; Primitiva Menéndez; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska-Bieniek; Katarzyna Durda; Natalia V Bogdanova; Natalia N Antonenkova; Thilo Dörk; Hoda Anton-Culver; Susan L Neuhausen; Argyrios Ziogas; Leslie Bernstein; Peter Devilee; Robert A E M Tollenaar; Caroline Seynaeve; Christi J van Asperen; Angela Cox; Simon S Cross; Malcolm W R Reed; Elza Khusnutdinova; Marina Bermisheva; Darya Prokofyeva; Zalina Takhirova; Alfons Meindl; Rita K Schmutzler; Christian Sutter; Rongxi Yang; Peter Schürmann; Michael Bremer; Hans Christiansen; Tjoung-Won Park-Simon; Peter Hillemanns; Pascal Guénel; Thérèse Truong; Florence Menegaux; Marie Sanchez; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Valeria Pensotti; John L Hopper; Helen Tsimiklis; Carmel Apicella; Melissa C Southey; Hiltrud Brauch; Thomas Brüning; Yon-Dschun Ko; Alice J Sigurdson; Michele M Doody; Ute Hamann; Diana Torres; Hans-Ulrich Ulmer; Asta Försti; Elinor J Sawyer; Ian Tomlinson; Michael J Kerin; Nicola Miller; Irene L Andrulis; Julia A Knight; Gord Glendon; Anna Marie Mulligan; Georgia Chenevix-Trench; Rosemary Balleine; Graham G Giles; Roger L Milne; Catriona McLean; Annika Lindblom; Sara Margolin; Christopher A Haiman; Brian E Henderson; Fredrick Schumacher; Loic Le Marchand; Ursula Eilber; Shan Wang-Gohrke; Maartje J Hooning; Antoinette Hollestelle; Ans M W van den Ouweland; Linetta B Koppert; Jane Carpenter; Christine Clarke; Rodney Scott; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Hermann Brenner; Volker Arndt; Christa Stegmaier; Aida Karina Dieffenbach; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Kenneth Offit; Joseph Vijai; Mark Robson; Rohini Rau-Murthy; Miriam Dwek; Ruth Swann; Katherine Annie Perkins; Mark S Goldberg; France Labrèche; Martine Dumont; Diana M Eccles; William J Tapper; Sajjad Rafiq; Esther M John; Alice S Whittemore; Susan Slager; Drakoulis Yannoukakos; Amanda E Toland; Song Yao; Wei Zheng; Sandra L Halverson; Anna González-Neira; Guillermo Pita; M Rosario Alonso; Nuria Álvarez; Daniel Herrero; Daniel C Tessier; Daniel Vincent; Francois Bacot; Craig Luccarini; Caroline Baynes; Shahana Ahmed; Mel Maranian; Catherine S Healey; Jacques Simard; Per Hall; Douglas F Easton; Montserrat Garcia-Closas

doi:10.1093/jnci/djv036

Prediction of breast cancer risk based on profiling with common genetic variants

Nasim Mavaddat, Paul D P Pharoah, Kyriaki Michailidou, Jonathan Tyrer, Mark N Brook, Manjeet K Bolla, Qin Wang, Joe Dennis, Alison M Dunning, Mitul Shah, Robert Luben, Judith Brown, Stig E Bojesen, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Kamila Czene, Hatef Darabi, Mikael Eriksson, Julian PetoIsabel Dos-Santos-Silva, Frank Dudbridge, Nichola Johnson, Marjanka K Schmidt, Annegien Broeks, Senno Verhoef, Emiel J Rutgers, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J Schoemaker, Jonine Figueroa, Stephen J Chanock, Louise Brinton, Jolanta Lissowska, Fergus J Couch, Janet E Olson, Celine Vachon, Vernon S Pankratz, Diether Lambrechts, Hans Wildiers, Chantal Van Ongeval, Erik van Limbergen, Vessela Kristensen, Grethe Grenaker Alnæs, Silje Nord, Anne-Lise Borresen-Dale, Heli Nevanlinna, Taru A Muranen, Kristiina Aittomäki, Carl Blomqvist, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Peter A Fasching, Lothar Haeberle, Arif B Ekici, Matthias W Beckmann, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Amy Trentham-Dietz, Polly Newcomb, Linda Titus, Kathleen M Egan, David J Hunter, Sara Lindstrom, Rulla M Tamimi, Peter Kraft, Nazneen Rahman, Clare Turnbull, Anthony Renwick, Sheila Seal, Jingmei Li, Jianjun Liu, Keith Humphreys, Javier Benitez, M Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Natalia V Bogdanova, Natalia N Antonenkova, Thilo Dörk, Hoda Anton-Culver, Susan L Neuhausen, Argyrios Ziogas, Leslie Bernstein, Peter Devilee, Robert A E M Tollenaar, Caroline Seynaeve, Christi J van Asperen, Angela Cox, Simon S Cross, Malcolm W R Reed, Elza Khusnutdinova, Marina Bermisheva, Darya Prokofyeva, Zalina Takhirova, Alfons Meindl, Rita K Schmutzler, Christian Sutter, Rongxi Yang, Peter Schürmann, Michael Bremer, Hans Christiansen, Tjoung-Won Park-Simon, Peter Hillemanns, Pascal Guénel, Thérèse Truong, Florence Menegaux, Marie Sanchez, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Valeria Pensotti, John L Hopper, Helen Tsimiklis, Carmel Apicella, Melissa C Southey, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Ko, Alice J Sigurdson, Michele M Doody, Ute Hamann, Diana Torres, Hans-Ulrich Ulmer, Asta Försti, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Irene L Andrulis, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Georgia Chenevix-Trench, Rosemary Balleine, Graham G Giles, Roger L Milne, Catriona McLean, Annika Lindblom, Sara Margolin, Christopher A Haiman, Brian E Henderson, Fredrick Schumacher, Loic Le Marchand, Ursula Eilber, Shan Wang-Gohrke, Maartje J Hooning, Antoinette Hollestelle, Ans M W van den Ouweland, Linetta B Koppert, Jane Carpenter, Christine Clarke, Rodney Scott, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Hermann Brenner, Volker Arndt, Christa Stegmaier, Aida Karina Dieffenbach, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Kenneth Offit, Joseph Vijai, Mark Robson, Rohini Rau-Murthy, Miriam Dwek, Ruth Swann, Katherine Annie Perkins, Mark S Goldberg, France Labrèche, Martine Dumont, Diana M Eccles, William J Tapper, Sajjad Rafiq, Esther M John, Alice S Whittemore, Susan Slager, Drakoulis Yannoukakos, Amanda E Toland, Song Yao, Wei Zheng, Sandra L Halverson, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Nuria Álvarez, Daniel Herrero, Daniel C Tessier, Daniel Vincent, Francois Bacot, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S Healey, Jacques Simard, Per Hall, Douglas F Easton, Montserrat Garcia-Closas

Institut for Klinisk Medicin

294 Citationer (Scopus)

Abstract

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.

METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.

RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.

CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Originalsprog	Engelsk
Artikelnummer	djv036
Tidsskrift	National Cancer Institute. Journal (Print)
Vol/bind	107
Udgave nummer	5
Sider (fra-til)	1-15
Antal sider	15
ISSN	0027-8874
DOI	https://doi.org/10.1093/jnci/djv036
Status	Udgivet - 1 maj 2015

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Mavaddat, N., Pharoah, P. D. P., Michailidou, K., Tyrer, J., Brook, M. N., Bolla, M. K., Wang, Q., Dennis, J., Dunning, A. M., Shah, M., Luben, R., Brown, J., Bojesen, S. E., Nordestgaard, B. G., Nielsen, S. F., Flyger, H., Czene, K., Darabi, H., Eriksson, M., ... Garcia-Closas, M. (2015). Prediction of breast cancer risk based on profiling with common genetic variants. National Cancer Institute. Journal (Print), 107(5), 1-15. [djv036]. https://doi.org/10.1093/jnci/djv036

Mavaddat, N, Pharoah, PDP, Michailidou, K, Tyrer, J, Brook, MN, Bolla, MK, Wang, Q, Dennis, J, Dunning, AM, Shah, M, Luben, R, Brown, J, Bojesen, SE , Nordestgaard, BG, Nielsen, SF, Flyger, H, Czene, K, Darabi, H, Eriksson, M, Peto, J, Dos-Santos-Silva, I, Dudbridge, F, Johnson, N, Schmidt, MK, Broeks, A, Verhoef, S, Rutgers, EJ, Swerdlow, A, Ashworth, A, Orr, N, Schoemaker, MJ, Figueroa, J, Chanock, SJ, Brinton, L, Lissowska, J, Couch, FJ, Olson, JE, Vachon, C, Pankratz, VS, Lambrechts, D, Wildiers, H, Van Ongeval, C, van Limbergen, E, Kristensen, V, Grenaker Alnæs, G, Nord, S, Borresen-Dale, A-L, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Trentham-Dietz, A, Newcomb, P, Titus, L, Egan, KM, Hunter, DJ, Lindstrom, S, Tamimi, RM, Kraft, P, Rahman, N, Turnbull, C, Renwick, A, Seal, S, Li, J, Liu, J, Humphreys, K, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Menéndez, P, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Bogdanova, NV, Antonenkova, NN, Dörk, T, Anton-Culver, H, Neuhausen, SL, Ziogas, A, Bernstein, L, Devilee, P, Tollenaar, RAEM, Seynaeve, C, van Asperen, CJ, Cox, A, Cross, SS, Reed, MWR, Khusnutdinova, E, Bermisheva, M, Prokofyeva, D, Takhirova, Z, Meindl, A, Schmutzler, RK, Sutter, C, Yang, R, Schürmann, P, Bremer, M, Christiansen, H, Park-Simon, T-W, Hillemanns, P, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Radice, P, Peterlongo, P, Manoukian, S, Pensotti, V, Hopper, JL, Tsimiklis, H, Apicella, C, Southey, MC, Brauch, H, Brüning, T, Ko, Y-D, Sigurdson, AJ, Doody, MM, Hamann, U, Torres, D, Ulmer, H-U, Försti, A, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Andrulis, IL, Knight, JA, Glendon, G, Marie Mulligan, A, Chenevix-Trench, G, Balleine, R, Giles, GG, Milne, RL, McLean, C, Lindblom, A, Margolin, S, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Eilber, U, Wang-Gohrke, S, Hooning, MJ, Hollestelle, A, van den Ouweland, AMW, Koppert, LB, Carpenter, J, Clarke, C, Scott, R, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Brenner, H, Arndt, V, Stegmaier, C, Karina Dieffenbach, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Offit, K, Vijai, J, Robson, M, Rau-Murthy, R, Dwek, M, Swann, R, Annie Perkins, K, Goldberg, MS, Labrèche, F, Dumont, M, Eccles, DM, Tapper, WJ, Rafiq, S, John, EM, Whittemore, AS, Slager, S, Yannoukakos, D, Toland, AE, Yao, S, Zheng, W, Halverson, SL, González-Neira, A, Pita, G, Rosario Alonso, M, Álvarez, N, Herrero, D, Tessier, DC, Vincent, D, Bacot, F, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Healey, CS, Simard, J, Hall, P, Easton, DF & Garcia-Closas, M 2015, 'Prediction of breast cancer risk based on profiling with common genetic variants', National Cancer Institute. Journal (Print), bind 107, nr. 5, djv036, s. 1-15. https://doi.org/10.1093/jnci/djv036

@article{69c617c1f94c463d9bc21d8e7162000b,

title = "Prediction of breast cancer risk based on profiling with common genetic variants",

abstract = "BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.",

keywords = "Adult, Aged, Biomarkers, Tumor, Breast Neoplasms, Europe, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Predictive Value of Tests, Receptors, Estrogen, Risk Assessment, Risk Factors",

author = "Nasim Mavaddat and Pharoah, {Paul D P} and Kyriaki Michailidou and Jonathan Tyrer and Brook, {Mark N} and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Dunning, {Alison M} and Mitul Shah and Robert Luben and Judith Brown and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Henrik Flyger and Kamila Czene and Hatef Darabi and Mikael Eriksson and Julian Peto and Isabel Dos-Santos-Silva and Frank Dudbridge and Nichola Johnson and Schmidt, {Marjanka K} and Annegien Broeks and Senno Verhoef and Rutgers, {Emiel J} and Anthony Swerdlow and Alan Ashworth and Nick Orr and Schoemaker, {Minouk J} and Jonine Figueroa and Chanock, {Stephen J} and Louise Brinton and Jolanta Lissowska and Couch, {Fergus J} and Olson, {Janet E} and Celine Vachon and Pankratz, {Vernon S} and Diether Lambrechts and Hans Wildiers and {Van Ongeval}, Chantal and {van Limbergen}, Erik and Vessela Kristensen and {Grenaker Aln{\ae}s}, Grethe and Silje Nord and Anne-Lise Borresen-Dale and Heli Nevanlinna and Muranen, {Taru A} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Fasching, {Peter A} and Lothar Haeberle and Ekici, {Arif B} and Beckmann, {Matthias W} and Barbara Burwinkel and Frederik Marme and Andreas Schneeweiss and Christof Sohn and Amy Trentham-Dietz and Polly Newcomb and Linda Titus and Egan, {Kathleen M} and Hunter, {David J} and Sara Lindstrom and Tamimi, {Rulla M} and Peter Kraft and Nazneen Rahman and Clare Turnbull and Anthony Renwick and Sheila Seal and Jingmei Li and Jianjun Liu and Keith Humphreys and Javier Benitez and {Pilar Zamora}, M and {Arias Perez}, {Jose Ignacio} and Primitiva Men{\'e}ndez and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Bogdanova, {Natalia V} and Antonenkova, {Natalia N} and Thilo D{\"o}rk and Hoda Anton-Culver and Neuhausen, {Susan L} and Argyrios Ziogas and Leslie Bernstein and Peter Devilee and Tollenaar, {Robert A E M} and Caroline Seynaeve and {van Asperen}, {Christi J} and Angela Cox and Cross, {Simon S} and Reed, {Malcolm W R} and Elza Khusnutdinova and Marina Bermisheva and Darya Prokofyeva and Zalina Takhirova and Alfons Meindl and Schmutzler, {Rita K} and Christian Sutter and Rongxi Yang and Peter Sch{\"u}rmann and Michael Bremer and Hans Christiansen and Tjoung-Won Park-Simon and Peter Hillemanns and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Marie Sanchez and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Valeria Pensotti and Hopper, {John L} and Helen Tsimiklis and Carmel Apicella and Southey, {Melissa C} and Hiltrud Brauch and Thomas Br{\"u}ning and Yon-Dschun Ko and Sigurdson, {Alice J} and Doody, {Michele M} and Ute Hamann and Diana Torres and Hans-Ulrich Ulmer and Asta F{\"o}rsti and Sawyer, {Elinor J} and Ian Tomlinson and Kerin, {Michael J} and Nicola Miller and Andrulis, {Irene L} and Knight, {Julia A} and Gord Glendon and {Marie Mulligan}, Anna and Georgia Chenevix-Trench and Rosemary Balleine and Giles, {Graham G} and Milne, {Roger L} and Catriona McLean and Annika Lindblom and Sara Margolin and Haiman, {Christopher A} and Henderson, {Brian E} and Fredrick Schumacher and {Le Marchand}, Loic and Ursula Eilber and Shan Wang-Gohrke and Hooning, {Maartje J} and Antoinette Hollestelle and {van den Ouweland}, {Ans M W} and Koppert, {Linetta B} and Jane Carpenter and Christine Clarke and Rodney Scott and Arto Mannermaa and Vesa Kataja and Veli-Matti Kosma and Hartikainen, {Jaana M} and Hermann Brenner and Volker Arndt and Christa Stegmaier and {Karina Dieffenbach}, Aida and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Kenneth Offit and Joseph Vijai and Mark Robson and Rohini Rau-Murthy and Miriam Dwek and Ruth Swann and {Annie Perkins}, Katherine and Goldberg, {Mark S} and France Labr{\`e}che and Martine Dumont and Eccles, {Diana M} and Tapper, {William J} and Sajjad Rafiq and John, {Esther M} and Whittemore, {Alice S} and Susan Slager and Drakoulis Yannoukakos and Toland, {Amanda E} and Song Yao and Wei Zheng and Halverson, {Sandra L} and Anna Gonz{\'a}lez-Neira and Guillermo Pita and {Rosario Alonso}, M and Nuria {\'A}lvarez and Daniel Herrero and Tessier, {Daniel C} and Daniel Vincent and Francois Bacot and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Mel Maranian and Healey, {Catherine S} and Jacques Simard and Per Hall and Easton, {Douglas F} and Montserrat Garcia-Closas",

note = "{\textcopyright} The Author 2015. Published by Oxford University Press.",

year = "2015",

month = may,

day = "1",

doi = "10.1093/jnci/djv036",

language = "English",

volume = "107",

pages = "1--15",

journal = "National Cancer Institute. Journal (Print)",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "5",

}

TY - JOUR

T1 - Prediction of breast cancer risk based on profiling with common genetic variants

AU - Mavaddat, Nasim

AU - Pharoah, Paul D P

AU - Michailidou, Kyriaki

AU - Tyrer, Jonathan

AU - Brook, Mark N

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Dunning, Alison M

AU - Shah, Mitul

AU - Luben, Robert

AU - Brown, Judith

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Flyger, Henrik

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Peto, Julian

AU - Dos-Santos-Silva, Isabel

AU - Dudbridge, Frank

AU - Johnson, Nichola

AU - Schmidt, Marjanka K

AU - Broeks, Annegien

AU - Verhoef, Senno

AU - Rutgers, Emiel J

AU - Swerdlow, Anthony

AU - Ashworth, Alan

AU - Orr, Nick

AU - Schoemaker, Minouk J

AU - Figueroa, Jonine

AU - Chanock, Stephen J

AU - Brinton, Louise

AU - Lissowska, Jolanta

AU - Couch, Fergus J

AU - Olson, Janet E

AU - Vachon, Celine

AU - Pankratz, Vernon S

AU - Lambrechts, Diether

AU - Wildiers, Hans

AU - Van Ongeval, Chantal

AU - van Limbergen, Erik

AU - Kristensen, Vessela

AU - Grenaker Alnæs, Grethe

AU - Nord, Silje

AU - Borresen-Dale, Anne-Lise

AU - Nevanlinna, Heli

AU - Muranen, Taru A

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Fasching, Peter A

AU - Haeberle, Lothar

AU - Ekici, Arif B

AU - Beckmann, Matthias W

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Trentham-Dietz, Amy

AU - Newcomb, Polly

AU - Titus, Linda

AU - Egan, Kathleen M

AU - Hunter, David J

AU - Lindstrom, Sara

AU - Tamimi, Rulla M

AU - Kraft, Peter

AU - Rahman, Nazneen

AU - Turnbull, Clare

AU - Renwick, Anthony

AU - Seal, Sheila

AU - Li, Jingmei

AU - Liu, Jianjun

AU - Humphreys, Keith

AU - Benitez, Javier

AU - Pilar Zamora, M

AU - Arias Perez, Jose Ignacio

AU - Menéndez, Primitiva

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Bogdanova, Natalia V

AU - Antonenkova, Natalia N

AU - Dörk, Thilo

AU - Anton-Culver, Hoda

AU - Neuhausen, Susan L

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Devilee, Peter

AU - Tollenaar, Robert A E M

AU - Seynaeve, Caroline

AU - van Asperen, Christi J

AU - Cox, Angela

AU - Cross, Simon S

AU - Reed, Malcolm W R

AU - Khusnutdinova, Elza

AU - Bermisheva, Marina

AU - Prokofyeva, Darya

AU - Takhirova, Zalina

AU - Meindl, Alfons

AU - Schmutzler, Rita K

AU - Sutter, Christian

AU - Yang, Rongxi

AU - Schürmann, Peter

AU - Bremer, Michael

AU - Christiansen, Hans

AU - Park-Simon, Tjoung-Won

AU - Hillemanns, Peter

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Sanchez, Marie

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Pensotti, Valeria

AU - Hopper, John L

AU - Tsimiklis, Helen

AU - Apicella, Carmel

AU - Southey, Melissa C

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon-Dschun

AU - Sigurdson, Alice J

AU - Doody, Michele M

AU - Hamann, Ute

AU - Torres, Diana

AU - Ulmer, Hans-Ulrich

AU - Försti, Asta

AU - Sawyer, Elinor J

AU - Tomlinson, Ian

AU - Kerin, Michael J

AU - Miller, Nicola

AU - Andrulis, Irene L

AU - Knight, Julia A

AU - Glendon, Gord

AU - Marie Mulligan, Anna

AU - Chenevix-Trench, Georgia

AU - Balleine, Rosemary

AU - Giles, Graham G

AU - Milne, Roger L

AU - McLean, Catriona

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Eilber, Ursula

AU - Wang-Gohrke, Shan

AU - Hooning, Maartje J

AU - Hollestelle, Antoinette

AU - van den Ouweland, Ans M W

AU - Koppert, Linetta B

AU - Carpenter, Jane

AU - Clarke, Christine

AU - Scott, Rodney

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli-Matti

AU - Hartikainen, Jaana M

AU - Brenner, Hermann

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Karina Dieffenbach, Aida

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Offit, Kenneth

AU - Vijai, Joseph

AU - Robson, Mark

AU - Rau-Murthy, Rohini

AU - Dwek, Miriam

AU - Swann, Ruth

AU - Annie Perkins, Katherine

AU - Goldberg, Mark S

AU - Labrèche, France

AU - Dumont, Martine

AU - Eccles, Diana M

AU - Tapper, William J

AU - Rafiq, Sajjad

AU - John, Esther M

AU - Whittemore, Alice S

AU - Slager, Susan

AU - Yannoukakos, Drakoulis

AU - Toland, Amanda E

AU - Yao, Song

AU - Zheng, Wei

AU - Halverson, Sandra L

AU - González-Neira, Anna

AU - Pita, Guillermo

AU - Rosario Alonso, M

AU - Álvarez, Nuria

AU - Herrero, Daniel

AU - Tessier, Daniel C

AU - Vincent, Daniel

AU - Bacot, Francois

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Ahmed, Shahana

AU - Maranian, Mel

AU - Healey, Catherine S

AU - Simard, Jacques

AU - Hall, Per

AU - Easton, Douglas F

AU - Garcia-Closas, Montserrat

PY - 2015/5/1

Y1 - 2015/5/1

N2 - BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

AB - BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

KW - Adult

KW - Aged

KW - Biomarkers, Tumor

KW - Breast Neoplasms

KW - Europe

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Middle Aged

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Predictive Value of Tests

KW - Receptors, Estrogen

KW - Risk Assessment

KW - Risk Factors

U2 - 10.1093/jnci/djv036

DO - 10.1093/jnci/djv036

M3 - Journal article

C2 - 25855707

SN - 0027-8874

VL - 107

SP - 1

EP - 15

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

IS - 5

M1 - djv036

ER -

Prediction of breast cancer risk based on profiling with common genetic variants

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