Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status

Anika Hüsing, Federico Canzian, Lars Beckmann, Montserrat Garcia-Closas, W. Ryan Diver, Michael J. Thun, Christine D. Berg, Robert N. Hoover, Regina G. Ziegler, Jonine D. Figueroa, Claudine Isaacs, Anja Olsen, Vivian Viallon, Heiner Boeing, Giovanna Masala, Dimitrios Trichopoulos, Petra H M Peeters, Eiliv Lund, Eva Ardanaz, Kay Tee Khaw & 17 others Per Lenner, Laurence N. Kolonel, Daniel O. Stram, Loïc Le Marchand, Catherine A. McCarty, Julie E. Buring, I. Min Lee, Shumin Zhang, Sara Lindström, Susan E. Hankinson, Elio Riboli, David J. Hunter, Brian E. Henderson, Stephen J. Chanock, Christopher A. Haiman, Peter Kraft, Rudolf Kaaks

Research output: Contribution to journalArticle

Abstract

Objective: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormonereceptor status has not been considered in this context. In this study we investigated the predictive capacity of 32 GWAS-detected common variants for breast cancer risk, alone and in combination with classical risk factors, and for tumours with different hormone receptor status. Material and methods: Within the Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast cancer cases and 7827 matched controls of European ancestry, with data on classical breast cancer risk factors and 32 common gene variants identified through GWAS. Discriminatory ability with respect to breast cancer of specific hormone receptor-status was assessed with the age adjusted and cohort-adjusted concordance statistic (AUROCa). Absolute risk scores were calculated with external reference data. Integrated discrimination improvement was used to measure improvements in risk prediction. Results We found a small but steady increase in discriminatory ability with increasing numbers of genetic variants included in the model (difference in AUROCa going from 2.7% to 4%). Discriminatory ability for all models varied strongly by hormone receptor status. Discussion and conclusions Adding information on common polymorphisms provides small but statistically significant improvements in the quality of breast cancer risk prediction models. We consistently observed better performance for receptor-positive cases, but the gain in discriminatory quality is not sufficient for clinical application.

Original languageEnglish (US)
Pages (from-to)601-608
Number of pages8
JournalJournal of Medical Genetics
Volume49
Issue number9
DOIs
StatePublished - Sep 2012
Externally publishedYes

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Hormones
Breast Neoplasms
Genome-Wide Association Study
Quality Improvement
Prostatic Neoplasms
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Hüsing, A., Canzian, F., Beckmann, L., Garcia-Closas, M., Diver, W. R., Thun, M. J., ... Kaaks, R. (2012). Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status. Journal of Medical Genetics, 49(9), 601-608. https://doi.org/10.1136/jmedgenet-2011-100716

Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status. / Hüsing, Anika; Canzian, Federico; Beckmann, Lars; Garcia-Closas, Montserrat; Diver, W. Ryan; Thun, Michael J.; Berg, Christine D.; Hoover, Robert N.; Ziegler, Regina G.; Figueroa, Jonine D.; Isaacs, Claudine; Olsen, Anja; Viallon, Vivian; Boeing, Heiner; Masala, Giovanna; Trichopoulos, Dimitrios; Peeters, Petra H M; Lund, Eiliv; Ardanaz, Eva; Khaw, Kay Tee; Lenner, Per; Kolonel, Laurence N.; Stram, Daniel O.; Le Marchand, Loïc; McCarty, Catherine A.; Buring, Julie E.; Lee, I. Min; Zhang, Shumin; Lindström, Sara; Hankinson, Susan E.; Riboli, Elio; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Haiman, Christopher A.; Kraft, Peter; Kaaks, Rudolf.

In: Journal of Medical Genetics, Vol. 49, No. 9, 09.2012, p. 601-608.

Research output: Contribution to journalArticle

Hüsing, A, Canzian, F, Beckmann, L, Garcia-Closas, M, Diver, WR, Thun, MJ, Berg, CD, Hoover, RN, Ziegler, RG, Figueroa, JD, Isaacs, C, Olsen, A, Viallon, V, Boeing, H, Masala, G, Trichopoulos, D, Peeters, PHM, Lund, E, Ardanaz, E, Khaw, KT, Lenner, P, Kolonel, LN, Stram, DO, Le Marchand, L, McCarty, CA, Buring, JE, Lee, IM, Zhang, S, Lindström, S, Hankinson, SE, Riboli, E, Hunter, DJ, Henderson, BE, Chanock, SJ, Haiman, CA, Kraft, P & Kaaks, R 2012, 'Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status', Journal of Medical Genetics, vol. 49, no. 9, pp. 601-608. https://doi.org/10.1136/jmedgenet-2011-100716
Hüsing, Anika ; Canzian, Federico ; Beckmann, Lars ; Garcia-Closas, Montserrat ; Diver, W. Ryan ; Thun, Michael J. ; Berg, Christine D. ; Hoover, Robert N. ; Ziegler, Regina G. ; Figueroa, Jonine D. ; Isaacs, Claudine ; Olsen, Anja ; Viallon, Vivian ; Boeing, Heiner ; Masala, Giovanna ; Trichopoulos, Dimitrios ; Peeters, Petra H M ; Lund, Eiliv ; Ardanaz, Eva ; Khaw, Kay Tee ; Lenner, Per ; Kolonel, Laurence N. ; Stram, Daniel O. ; Le Marchand, Loïc ; McCarty, Catherine A. ; Buring, Julie E. ; Lee, I. Min ; Zhang, Shumin ; Lindström, Sara ; Hankinson, Susan E. ; Riboli, Elio ; Hunter, David J. ; Henderson, Brian E. ; Chanock, Stephen J. ; Haiman, Christopher A. ; Kraft, Peter ; Kaaks, Rudolf. / Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 9. pp. 601-608.
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abstract = "Objective: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormonereceptor status has not been considered in this context. In this study we investigated the predictive capacity of 32 GWAS-detected common variants for breast cancer risk, alone and in combination with classical risk factors, and for tumours with different hormone receptor status. Material and methods: Within the Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast cancer cases and 7827 matched controls of European ancestry, with data on classical breast cancer risk factors and 32 common gene variants identified through GWAS. Discriminatory ability with respect to breast cancer of specific hormone receptor-status was assessed with the age adjusted and cohort-adjusted concordance statistic (AUROCa). Absolute risk scores were calculated with external reference data. Integrated discrimination improvement was used to measure improvements in risk prediction. Results We found a small but steady increase in discriminatory ability with increasing numbers of genetic variants included in the model (difference in AUROCa going from 2.7{\%} to 4{\%}). Discriminatory ability for all models varied strongly by hormone receptor status. Discussion and conclusions Adding information on common polymorphisms provides small but statistically significant improvements in the quality of breast cancer risk prediction models. We consistently observed better performance for receptor-positive cases, but the gain in discriminatory quality is not sufficient for clinical application.",
author = "Anika H{\"u}sing and Federico Canzian and Lars Beckmann and Montserrat Garcia-Closas and Diver, {W. Ryan} and Thun, {Michael J.} and Berg, {Christine D.} and Hoover, {Robert N.} and Ziegler, {Regina G.} and Figueroa, {Jonine D.} and Claudine Isaacs and Anja Olsen and Vivian Viallon and Heiner Boeing and Giovanna Masala and Dimitrios Trichopoulos and Peeters, {Petra H M} and Eiliv Lund and Eva Ardanaz and Khaw, {Kay Tee} and Per Lenner and Kolonel, {Laurence N.} and Stram, {Daniel O.} and {Le Marchand}, Lo{\"i}c and McCarty, {Catherine A.} and Buring, {Julie E.} and Lee, {I. Min} and Shumin Zhang and Sara Lindstr{\"o}m and Hankinson, {Susan E.} and Elio Riboli and Hunter, {David J.} and Henderson, {Brian E.} and Chanock, {Stephen J.} and Haiman, {Christopher A.} and Peter Kraft and Rudolf Kaaks",
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T1 - Prediction of breast cancer risk by genetic risk factors, overall and by hormone receptor status

AU - Hüsing, Anika

AU - Canzian, Federico

AU - Beckmann, Lars

AU - Garcia-Closas, Montserrat

AU - Diver, W. Ryan

AU - Thun, Michael J.

AU - Berg, Christine D.

AU - Hoover, Robert N.

AU - Ziegler, Regina G.

AU - Figueroa, Jonine D.

AU - Isaacs, Claudine

AU - Olsen, Anja

AU - Viallon, Vivian

AU - Boeing, Heiner

AU - Masala, Giovanna

AU - Trichopoulos, Dimitrios

AU - Peeters, Petra H M

AU - Lund, Eiliv

AU - Ardanaz, Eva

AU - Khaw, Kay Tee

AU - Lenner, Per

AU - Kolonel, Laurence N.

AU - Stram, Daniel O.

AU - Le Marchand, Loïc

AU - McCarty, Catherine A.

AU - Buring, Julie E.

AU - Lee, I. Min

AU - Zhang, Shumin

AU - Lindström, Sara

AU - Hankinson, Susan E.

AU - Riboli, Elio

AU - Hunter, David J.

AU - Henderson, Brian E.

AU - Chanock, Stephen J.

AU - Haiman, Christopher A.

AU - Kraft, Peter

AU - Kaaks, Rudolf

PY - 2012/9

Y1 - 2012/9

N2 - Objective: There is increasing interest in adding common genetic variants identified through genome wide association studies (GWAS) to breast cancer risk prediction models. First results from such models showed modest benefits in terms of risk discrimination. Heterogeneity of breast cancer as defined by hormonereceptor status has not been considered in this context. In this study we investigated the predictive capacity of 32 GWAS-detected common variants for breast cancer risk, alone and in combination with classical risk factors, and for tumours with different hormone receptor status. Material and methods: Within the Breast and Prostate Cancer Cohort Consortium, we analysed 6009 invasive breast cancer cases and 7827 matched controls of European ancestry, with data on classical breast cancer risk factors and 32 common gene variants identified through GWAS. Discriminatory ability with respect to breast cancer of specific hormone receptor-status was assessed with the age adjusted and cohort-adjusted concordance statistic (AUROCa). Absolute risk scores were calculated with external reference data. Integrated discrimination improvement was used to measure improvements in risk prediction. Results We found a small but steady increase in discriminatory ability with increasing numbers of genetic variants included in the model (difference in AUROCa going from 2.7% to 4%). Discriminatory ability for all models varied strongly by hormone receptor status. Discussion and conclusions Adding information on common polymorphisms provides small but statistically significant improvements in the quality of breast cancer risk prediction models. We consistently observed better performance for receptor-positive cases, but the gain in discriminatory quality is not sufficient for clinical application.

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