Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures

Jennifer Stone; D.J. Thompson; I. Dos Santos Silva; C. Scott; R.M. Tamimi; S. Lindstrom; P. Kraft; A. Hazra; J. Li; L. Eriksson; K. Czene; P. Hall; M. Jensen; J. Cunningham; J.E. Olson; K. Purrington; F.J. Couch; J. Brown; J. Leyland; R.M.L. Warren; R.N. Luben; K.T. Khaw; P. Smith; N.J. Wareham; S.M. Jud; K. Heusinger; M.W. Beckmann; J.A. Douglas; K.P. Shah; H.P. Chan; M.A. Helvie; L.L. Marchand; L.N. Kolonel; C. Woolcott; G. Maskarinec; C. Haiman; G.G. Giles; L. Baglietto; K. Krishnan; M.C. Southey; C. Apicella; I.L. Andrulis; J.A. Knight; G. Ursin; G.I.G. Alnaes; V.N. Kristensen; A.L. Borresen-Dale; I.T. Gram; M.K. Bolla; Q. Wang; K. Michailidou; J. Dennis; J. Simard; P. Pharoah; A.M. Dunning; D.F. Easton; P.A. Fasching; V.S. Pankratz; J.L. Hopper; C.M. Vachon

doi:10.1158/0008-5472.CAN-14-2012

Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures

Jennifer Stone, D.J. Thompson, I. Dos Santos Silva, C. Scott, R.M. Tamimi, S. Lindstrom, P. Kraft, A. Hazra, J. Li, L. Eriksson, K. Czene, P. Hall, M. Jensen, J. Cunningham, J.E. Olson, K. Purrington, F.J. Couch, J. Brown, J. Leyland, R.M.L. WarrenR.N. Luben, K.T. Khaw, P. Smith, N.J. Wareham, S.M. Jud, K. Heusinger, M.W. Beckmann, J.A. Douglas, K.P. Shah, H.P. Chan, M.A. Helvie, L.L. Marchand, L.N. Kolonel, C. Woolcott, G. Maskarinec, C. Haiman, G.G. Giles, L. Baglietto, K. Krishnan, M.C. Southey, C. Apicella, I.L. Andrulis, J.A. Knight, G. Ursin, G.I.G. Alnaes, V.N. Kristensen, A.L. Borresen-Dale, I.T. Gram, M.K. Bolla, Q. Wang, K. Michailidou, J. Dennis, J. Simard, P. Pharoah, A.M. Dunning, D.F. Easton, P.A. Fasching, V.S. Pankratz, J.L. Hopper, C.M. Vachon

Centre for Genetic Origins of Health and Diseases

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Abstract

© 2015 American Association for Cancer Research. Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210(ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679(EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.

Original language	English
Pages (from-to)	2457-2467
Journal	Cancer Research
Volume	75
Issue number	12
DOIs	https://doi.org/10.1158/0008-5472.CAN-14-2012
Publication status	Published - 15 Jun 2015

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Stone, J., Thompson, D. J., Dos Santos Silva, I., Scott, C., Tamimi, R. M., Lindstrom, S., Kraft, P., Hazra, A., Li, J., Eriksson, L., Czene, K., Hall, P., Jensen, M., Cunningham, J., Olson, J. E., Purrington, K., Couch, F. J., Brown, J., Leyland, J., ... Vachon, C. M. (2015). Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures. Cancer Research, 75(12), 2457-2467. https://doi.org/10.1158/0008-5472.CAN-14-2012

Stone, Jennifer ; Thompson, D.J. ; Dos Santos Silva, I. ; Scott, C. ; Tamimi, R.M. ; Lindstrom, S. ; Kraft, P. ; Hazra, A. ; Li, J. ; Eriksson, L. ; Czene, K. ; Hall, P. ; Jensen, M. ; Cunningham, J. ; Olson, J.E. ; Purrington, K. ; Couch, F.J. ; Brown, J. ; Leyland, J. ; Warren, R.M.L. ; Luben, R.N. ; Khaw, K.T. ; Smith, P. ; Wareham, N.J. ; Jud, S.M. ; Heusinger, K. ; Beckmann, M.W. ; Douglas, J.A. ; Shah, K.P. ; Chan, H.P. ; Helvie, M.A. ; Marchand, L.L. ; Kolonel, L.N. ; Woolcott, C. ; Maskarinec, G. ; Haiman, C. ; Giles, G.G. ; Baglietto, L. ; Krishnan, K. ; Southey, M.C. ; Apicella, C. ; Andrulis, I.L. ; Knight, J.A. ; Ursin, G. ; Alnaes, G.I.G. ; Kristensen, V.N. ; Borresen-Dale, A.L. ; Gram, I.T. ; Bolla, M.K. ; Wang, Q. ; Michailidou, K. ; Dennis, J. ; Simard, J. ; Pharoah, P. ; Dunning, A.M. ; Easton, D.F. ; Fasching, P.A. ; Pankratz, V.S. ; Hopper, J.L. ; Vachon, C.M. / Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures. In: Cancer Research. 2015 ; Vol. 75, No. 12. pp. 2457-2467.

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title = "Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures",

abstract = "{\textcopyright} 2015 American Association for Cancer Research. Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210(ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679(EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.",

author = "Jennifer Stone and D.J. Thompson and {Dos Santos Silva}, I. and C. Scott and R.M. Tamimi and S. Lindstrom and P. Kraft and A. Hazra and J. Li and L. Eriksson and K. Czene and P. Hall and M. Jensen and J. Cunningham and J.E. Olson and K. Purrington and F.J. Couch and J. Brown and J. Leyland and R.M.L. Warren and R.N. Luben and K.T. Khaw and P. Smith and N.J. Wareham and S.M. Jud and K. Heusinger and M.W. Beckmann and J.A. Douglas and K.P. Shah and H.P. Chan and M.A. Helvie and L.L. Marchand and L.N. Kolonel and C. Woolcott and G. Maskarinec and C. Haiman and G.G. Giles and L. Baglietto and K. Krishnan and M.C. Southey and C. Apicella and I.L. Andrulis and J.A. Knight and G. Ursin and G.I.G. Alnaes and V.N. Kristensen and A.L. Borresen-Dale and I.T. Gram and M.K. Bolla and Q. Wang and K. Michailidou and J. Dennis and J. Simard and P. Pharoah and A.M. Dunning and D.F. Easton and P.A. Fasching and V.S. Pankratz and J.L. Hopper and C.M. Vachon",

year = "2015",

month = jun,

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doi = "10.1158/0008-5472.CAN-14-2012",

language = "English",

volume = "75",

pages = "2457--2467",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research (AACR)",

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Stone, J, Thompson, DJ, Dos Santos Silva, I, Scott, C, Tamimi, RM, Lindstrom, S, Kraft, P, Hazra, A, Li, J, Eriksson, L, Czene, K, Hall, P, Jensen, M, Cunningham, J, Olson, JE, Purrington, K, Couch, FJ, Brown, J, Leyland, J, Warren, RML, Luben, RN, Khaw, KT, Smith, P, Wareham, NJ, Jud, SM, Heusinger, K, Beckmann, MW, Douglas, JA, Shah, KP, Chan, HP, Helvie, MA, Marchand, LL, Kolonel, LN, Woolcott, C, Maskarinec, G, Haiman, C, Giles, GG, Baglietto, L, Krishnan, K, Southey, MC, Apicella, C, Andrulis, IL, Knight, JA, Ursin, G, Alnaes, GIG, Kristensen, VN, Borresen-Dale, AL, Gram, IT, Bolla, MK, Wang, Q, Michailidou, K, Dennis, J, Simard, J, Pharoah, P, Dunning, AM, Easton, DF, Fasching, PA, Pankratz, VS, Hopper, JL & Vachon, CM 2015, 'Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures', Cancer Research, vol. 75, no. 12, pp. 2457-2467. https://doi.org/10.1158/0008-5472.CAN-14-2012

Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures. / Stone, Jennifer; Thompson, D.J.; Dos Santos Silva, I.; Scott, C.; Tamimi, R.M.; Lindstrom, S.; Kraft, P.; Hazra, A.; Li, J.; Eriksson, L.; Czene, K.; Hall, P.; Jensen, M.; Cunningham, J.; Olson, J.E.; Purrington, K.; Couch, F.J.; Brown, J.; Leyland, J.; Warren, R.M.L.; Luben, R.N.; Khaw, K.T.; Smith, P.; Wareham, N.J.; Jud, S.M.; Heusinger, K.; Beckmann, M.W.; Douglas, J.A.; Shah, K.P.; Chan, H.P.; Helvie, M.A.; Marchand, L.L.; Kolonel, L.N.; Woolcott, C.; Maskarinec, G.; Haiman, C.; Giles, G.G.; Baglietto, L.; Krishnan, K.; Southey, M.C.; Apicella, C.; Andrulis, I.L.; Knight, J.A.; Ursin, G.; Alnaes, G.I.G.; Kristensen, V.N.; Borresen-Dale, A.L.; Gram, I.T.; Bolla, M.K.; Wang, Q.; Michailidou, K.; Dennis, J.; Simard, J.; Pharoah, P.; Dunning, A.M.; Easton, D.F.; Fasching, P.A.; Pankratz, V.S.; Hopper, J.L.; Vachon, C.M.

In: Cancer Research, Vol. 75, No. 12, 15.06.2015, p. 2457-2467.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures

AU - Stone, Jennifer

AU - Thompson, D.J.

AU - Dos Santos Silva, I.

AU - Scott, C.

AU - Tamimi, R.M.

AU - Lindstrom, S.

AU - Kraft, P.

AU - Hazra, A.

AU - Li, J.

AU - Eriksson, L.

AU - Czene, K.

AU - Hall, P.

AU - Jensen, M.

AU - Cunningham, J.

AU - Olson, J.E.

AU - Purrington, K.

AU - Couch, F.J.

AU - Brown, J.

AU - Leyland, J.

AU - Warren, R.M.L.

AU - Luben, R.N.

AU - Khaw, K.T.

AU - Smith, P.

AU - Wareham, N.J.

AU - Jud, S.M.

AU - Heusinger, K.

AU - Beckmann, M.W.

AU - Douglas, J.A.

AU - Shah, K.P.

AU - Chan, H.P.

AU - Helvie, M.A.

AU - Marchand, L.L.

AU - Kolonel, L.N.

AU - Woolcott, C.

AU - Maskarinec, G.

AU - Haiman, C.

AU - Giles, G.G.

AU - Baglietto, L.

AU - Krishnan, K.

AU - Southey, M.C.

AU - Apicella, C.

AU - Andrulis, I.L.

AU - Knight, J.A.

AU - Ursin, G.

AU - Alnaes, G.I.G.

AU - Kristensen, V.N.

AU - Borresen-Dale, A.L.

AU - Gram, I.T.

AU - Bolla, M.K.

AU - Wang, Q.

AU - Michailidou, K.

AU - Dennis, J.

AU - Simard, J.

AU - Pharoah, P.

AU - Dunning, A.M.

AU - Easton, D.F.

AU - Fasching, P.A.

AU - Pankratz, V.S.

AU - Hopper, J.L.

AU - Vachon, C.M.

PY - 2015/6/15

Y1 - 2015/6/15

N2 - © 2015 American Association for Cancer Research. Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210(ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679(EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.

AB - © 2015 American Association for Cancer Research. Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210(ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P <10-5). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679(EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.

U2 - 10.1158/0008-5472.CAN-14-2012

DO - 10.1158/0008-5472.CAN-14-2012

M3 - Article

C2 - 25862352

VL - 75

SP - 2457

EP - 2467

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 12

ER -

Novel associations between common breast cancer susceptibility variants and risk-predicting mammographic density measures

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