Advanced

Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

Mavaddat, Nasim; Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M. and Shah, Mitul, et al. (2015) In Journal of the National Cancer Institute 107(5). p.036-036
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the National Cancer Institute
volume
107
issue
5
pages
036 - 036
publisher
Oxford University Press
external identifiers
  • wos:000355088600009
  • scopus:84928761946
ISSN
1460-2105
DOI
10.1093/jnci/djv036
language
English
LU publication?
yes
id
c4b613ce-c2cd-42d6-a46e-1af4cf77c371 (old id 7410749)
date added to LUP
2015-07-03 07:02:32
date last changed
2017-11-19 03:45:56
@article{c4b613ce-c2cd-42d6-a46e-1af4cf77c371,
  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.},
  author       = {Mavaddat, Nasim and Pharoah, Paul D. P. and Michailidou, Kyriaki and Tyrer, Jonathan and Brook, Mark N. and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Dunning, Alison M. and Shah, Mitul and Luben, Robert and Brown, Judith and Bojesen, Stig E. and Nordestgaard, Borge G. and Nielsen, Sune F. and Flyger, Henrik and Czene, Kamila and Darabi, Hatef and Eriksson, Mikael and Peto, Julian and dos-Santos-Silva, Isabel and Dudbridge, Frank and Johnson, Nichola and Schmidt, Marjanka K. and Broeks, Annegien and Verhoef, Senno and Rutgers, Emiel J. and Swerdlow, Anthony and Ashworth, Alan and Orr, Nick and Schoemaker, Minouk J. and Figueroa, Jonine and Chanock, Stephen J. and Brinton, Louise and Lissowska, Jolanta and Couch, Fergus J. and Olson, Janet E. and Vachon, Celine and Pankratz, Vernon S. and Lambrechts, Diether and Wildiers, Hans and Van Ongeval, Chantal and Van Limbergen, Erik and Kristensen, Vessela and Alnaes, Grethe Grenaker and Nord, Silje and Borresen-Dale, Anne-Lise and Nevanlinna, Heli and Muranen, Taru A. and Aittomaeki, Kristiina and Blomqvist, Carl and Chang-Claude, Jenny and Rudolph, Anja and Seibold, Petra and Flesch-Janys, Dieter and Fasching, Peter A. and Haeberle, Lothar and Ekici, Arif B. and Beckmann, Matthias W. and Burwinkel, Barbara and Marme, Frederik and Schneeweiss, Andreas and Sohn, Christof and Trentham-Dietz, Amy and Newcomb, Polly and Titus, Linda and Egan, Kathleen M. and Hunter, David J. and Lindstrom, Sara and Tamimi, Rulla M. and Kraft, Peter and Rahman, Nazneen and Turnbull, Clare and Renwick, Anthony and Seal, Sheila and Li, Jingmei and Liu, Jianjun and Humphreys, Keith and Benitez, Javier and Zamora, M. Pilar and Perez, Jose Ignacio Arias and Menendez, Primitiva and Jakubowska, Anna and Lubinski, Jan and Jaworska-Bieniek, Katarzyna and Durda, Katarzyna and Bogdanova, Natalia V. and Antonenkova, Natalia N. and Doerk, Thilo and Anton-Culver, Hoda and Neuhausen, Susan L. and Ziogas, Argyrios and Bernstein, Leslie and Devilee, Peter and Tollenaar, Robert A. E. M. and Seynaeve, Caroline and van Asperen, Christi J. and Cox, Angela and Cross, Simon S. and Reed, Malcolm W. R. and Khusnutdinova, Elza and Bermisheva, Marina and Prokofyeva, Darya and Takhirova, Zalina and Meindl, Alfons and Schmutzler, Rita K. and Sutter, Christian and Yang, Rongxi and Schuermann, Peter and Bremer, Michael and Christiansen, Hans and Park-Simon, Tjoung-Won and Hillemanns, Peter and Guenel, Pascal and Truong, Therese and Menegaux, Florence and Sanchez, Marie and Radice, Paolo and Peterlongo, Paolo and Manoukian, Siranoush and Pensotti, Valeria and Hopper, John L. and Tsimiklis, Helen and Apicella, Carmel and Southey, Melissa C. and Brauch, Hiltrud and Bruening, Thomas and Ko, Yon-Dschun and Sigurdson, Alice J. and Doody, Michele M. and Hamann, Ute and Torres, Diana and Ulmer, Hans-Ulrich and Försti, Asta and Sawyer, Elinor J. and Tomlinson, Ian and Kerin, Michael J. and Miller, Nicola and Andrulis, Irene L. and Knight, Julia A. and Glendon, Gord and Mulligan, Anna Marie and Chenevix-Trench, Georgia and Balleine, Rosemary and Giles, Graham G. and Milne, Roger L. and McLean, Catriona and Lindblom, Annika and Margolin, Sara and Haiman, Christopher A. and Henderson, Brian E. and Schumacher, Fredrick and Le Marchand, Loic and Eilber, Ursula and Wang-Gohrke, Shan and Hooning, Maartje J. and Hollestelle, Antoinette and van den Ouweland, Ans M. W. and Koppert, Linetta B. and Carpenter, Jane and Clarke, Christine and Scott, Rodney and Mannermaa, Arto and Kataja, Vesa and Kosma, Veli-Matti and Hartikainen, Jaana M. and Brenner, Hermann and Arndt, Volker and Stegmaier, Christa and Dieffenbach, Aida Karina and Winqvist, Robert and Pylkaes, Katri and Jukkola-Vuorinen, Arja and Grip, Mervi and Offit, Kenneth and Vijai, Joseph and Robson, Mark and Rau-Murthy, Rohini and Dwek, Miriam and Swann, Ruth and Perkins, Katherine Annie and Goldberg, Mark S. and Labreche, France and Dumont, Martine and Eccles, Diana M. and Tapper, William J. and Rafiq, Sajjad and John, Esther M. and Whittemore, Alice S. and Slager, Susan and Yannoukakos, Drakoulis and Toland, Amanda E. and Yao, Song and Zheng, Wei and Halverson, Sandra L. and Gonzalez-Neira, Anna and Pita, Guillermo and Alonso, M. Rosario and Alvarez, Nuria and Herrero, Daniel and Tessier, Daniel C. and Vincent, Daniel and Bacot, Francois and Luccarini, Craig and Baynes, Caroline and Ahmed, Shahana and Maranian, Mel and Healey, Catherine S. and Simard, Jacques and Hall, Per and Easton, Douglas F. and Garcia-Closas, Montserrat},
  issn         = {1460-2105},
  language     = {eng},
  number       = {5},
  pages        = {036--036},
  publisher    = {Oxford University Press},
  series       = {Journal of the National Cancer Institute},
  title        = {Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants},
  url          = {http://dx.doi.org/10.1093/jnci/djv036},
  volume       = {107},
  year         = {2015},
}