Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk

Celine M Vachon, Christopher G. Scott, Peter A. Fasching, Per Hall, Rulla M. Tamimi, Jingmei Li, Jennifer Stone, Carmel Apicella, Fabrice Odefrey, Gretchen L. Gierach, Sebastian M. Jud, Katharina Heusinger, Matthias W. Beckmann, Marina Pollan, Pablo Fernańdez-Navarro, Anna Gonzalez-Neira, Javier Benitez, Carla H. Van Gils, Mariëtte Lokate, N. Charlotte Onland-MoretPetra H M Peeters, Judith Brown, Jean Leyland, Jajini S. Varghese, Douglas F. Easton, Deborah J. Thompson, Robert N. Luben, Ruth M L Warren, Nicholas J. Wareham, Ruth J F Loos, Kay Tee Khaw, Giske Ursin, Eunjung Lee, Simon A. Gayther, Susan J. Ramus, Rosalind A. Eeles, Martin O. Leach, Gek Kwan-Lim, Fergus J Couch, Graham G. Giles, Laura Baglietto, Kavitha Krishnan, Melissa C. Southey, Loic Le Marchand, Laurence N. Kolonel, Christy Woolcott, Gertraud Maskarinec, Christopher A. Haiman, Kate Walker, Nichola Johnson, Valeria A. McCormack, Margarethe Biong, Grethe I G Alnaes, IngerTorhild Gram, Vessela N. Kristensen, Anne Lise Brøresen-Dale, Sara Lindstrom̈, Susan E. Hankinson, David J. Hunter, Irene L. Andrulis, Julia A. Knight, Norman F. Boyd, Jonine D. Figuero, Jolanta Lissowska, Ewa Wesolowska, Beata Peplonska, Agnieszka Bukowska, Edyta Reszka, JianJun Liu, Louise Eriksson, Kamila Czene, Tina Audley, Anna H. Wu, V. Shane Pankratz, John L. Hopper, Isabel Dos-Santos-Silva

Research output: Contribution to journalArticle

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Abstract

Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures. Methods: We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and nondense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, BMI, and menopausal status. Results: Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (P = 0.00005) and adjusted percent density (P = 0.001), whereas the A-allele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (P = 0.003), but not with adjusted dense area (P = 0.07). Conclusion: We identified two common breast cancer susceptibility variants associated with mammographic measures of radiodense tissue in the breast gland. Impact: We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association.

Original languageEnglish (US)
Pages (from-to)1156-1166
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number7
DOIs
StatePublished - Jul 2012

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Breast Neoplasms
Body Mass Index
Alleles
Breast Density
Penetrance
Linear Models
Breast
Cross-Sectional Studies
Phenotype

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. / Vachon, Celine M; Scott, Christopher G.; Fasching, Peter A.; Hall, Per; Tamimi, Rulla M.; Li, Jingmei; Stone, Jennifer; Apicella, Carmel; Odefrey, Fabrice; Gierach, Gretchen L.; Jud, Sebastian M.; Heusinger, Katharina; Beckmann, Matthias W.; Pollan, Marina; Fernańdez-Navarro, Pablo; Gonzalez-Neira, Anna; Benitez, Javier; Van Gils, Carla H.; Lokate, Mariëtte; Onland-Moret, N. Charlotte; Peeters, Petra H M; Brown, Judith; Leyland, Jean; Varghese, Jajini S.; Easton, Douglas F.; Thompson, Deborah J.; Luben, Robert N.; Warren, Ruth M L; Wareham, Nicholas J.; Loos, Ruth J F; Khaw, Kay Tee; Ursin, Giske; Lee, Eunjung; Gayther, Simon A.; Ramus, Susan J.; Eeles, Rosalind A.; Leach, Martin O.; Kwan-Lim, Gek; Couch, Fergus J; Giles, Graham G.; Baglietto, Laura; Krishnan, Kavitha; Southey, Melissa C.; Le Marchand, Loic; Kolonel, Laurence N.; Woolcott, Christy; Maskarinec, Gertraud; Haiman, Christopher A.; Walker, Kate; Johnson, Nichola; McCormack, Valeria A.; Biong, Margarethe; Alnaes, Grethe I G; Gram, IngerTorhild; Kristensen, Vessela N.; Brøresen-Dale, Anne Lise; Lindstrom̈, Sara; Hankinson, Susan E.; Hunter, David J.; Andrulis, Irene L.; Knight, Julia A.; Boyd, Norman F.; Figuero, Jonine D.; Lissowska, Jolanta; Wesolowska, Ewa; Peplonska, Beata; Bukowska, Agnieszka; Reszka, Edyta; Liu, JianJun; Eriksson, Louise; Czene, Kamila; Audley, Tina; Wu, Anna H.; Pankratz, V. Shane; Hopper, John L.; Dos-Santos-Silva, Isabel.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 7, 07.2012, p. 1156-1166.

Research output: Contribution to journalArticle

Vachon, CM, Scott, CG, Fasching, PA, Hall, P, Tamimi, RM, Li, J, Stone, J, Apicella, C, Odefrey, F, Gierach, GL, Jud, SM, Heusinger, K, Beckmann, MW, Pollan, M, Fernańdez-Navarro, P, Gonzalez-Neira, A, Benitez, J, Van Gils, CH, Lokate, M, Onland-Moret, NC, Peeters, PHM, Brown, J, Leyland, J, Varghese, JS, Easton, DF, Thompson, DJ, Luben, RN, Warren, RML, Wareham, NJ, Loos, RJF, Khaw, KT, Ursin, G, Lee, E, Gayther, SA, Ramus, SJ, Eeles, RA, Leach, MO, Kwan-Lim, G, Couch, FJ, Giles, GG, Baglietto, L, Krishnan, K, Southey, MC, Le Marchand, L, Kolonel, LN, Woolcott, C, Maskarinec, G, Haiman, CA, Walker, K, Johnson, N, McCormack, VA, Biong, M, Alnaes, GIG, Gram, I, Kristensen, VN, Brøresen-Dale, AL, Lindstrom̈, S, Hankinson, SE, Hunter, DJ, Andrulis, IL, Knight, JA, Boyd, NF, Figuero, JD, Lissowska, J, Wesolowska, E, Peplonska, B, Bukowska, A, Reszka, E, Liu, J, Eriksson, L, Czene, K, Audley, T, Wu, AH, Pankratz, VS, Hopper, JL & Dos-Santos-Silva, I 2012, 'Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 7, pp. 1156-1166. https://doi.org/10.1158/1055-9965.EPI-12-0066
Vachon, Celine M ; Scott, Christopher G. ; Fasching, Peter A. ; Hall, Per ; Tamimi, Rulla M. ; Li, Jingmei ; Stone, Jennifer ; Apicella, Carmel ; Odefrey, Fabrice ; Gierach, Gretchen L. ; Jud, Sebastian M. ; Heusinger, Katharina ; Beckmann, Matthias W. ; Pollan, Marina ; Fernańdez-Navarro, Pablo ; Gonzalez-Neira, Anna ; Benitez, Javier ; Van Gils, Carla H. ; Lokate, Mariëtte ; Onland-Moret, N. Charlotte ; Peeters, Petra H M ; Brown, Judith ; Leyland, Jean ; Varghese, Jajini S. ; Easton, Douglas F. ; Thompson, Deborah J. ; Luben, Robert N. ; Warren, Ruth M L ; Wareham, Nicholas J. ; Loos, Ruth J F ; Khaw, Kay Tee ; Ursin, Giske ; Lee, Eunjung ; Gayther, Simon A. ; Ramus, Susan J. ; Eeles, Rosalind A. ; Leach, Martin O. ; Kwan-Lim, Gek ; Couch, Fergus J ; Giles, Graham G. ; Baglietto, Laura ; Krishnan, Kavitha ; Southey, Melissa C. ; Le Marchand, Loic ; Kolonel, Laurence N. ; Woolcott, Christy ; Maskarinec, Gertraud ; Haiman, Christopher A. ; Walker, Kate ; Johnson, Nichola ; McCormack, Valeria A. ; Biong, Margarethe ; Alnaes, Grethe I G ; Gram, IngerTorhild ; Kristensen, Vessela N. ; Brøresen-Dale, Anne Lise ; Lindstrom̈, Sara ; Hankinson, Susan E. ; Hunter, David J. ; Andrulis, Irene L. ; Knight, Julia A. ; Boyd, Norman F. ; Figuero, Jonine D. ; Lissowska, Jolanta ; Wesolowska, Ewa ; Peplonska, Beata ; Bukowska, Agnieszka ; Reszka, Edyta ; Liu, JianJun ; Eriksson, Louise ; Czene, Kamila ; Audley, Tina ; Wu, Anna H. ; Pankratz, V. Shane ; Hopper, John L. ; Dos-Santos-Silva, Isabel. / Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 7. pp. 1156-1166.
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title = "Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk",
abstract = "Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures. Methods: We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and nondense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, BMI, and menopausal status. Results: Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (P = 0.00005) and adjusted percent density (P = 0.001), whereas the A-allele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (P = 0.003), but not with adjusted dense area (P = 0.07). Conclusion: We identified two common breast cancer susceptibility variants associated with mammographic measures of radiodense tissue in the breast gland. Impact: We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association.",
author = "Vachon, {Celine M} and Scott, {Christopher G.} and Fasching, {Peter A.} and Per Hall and Tamimi, {Rulla M.} and Jingmei Li and Jennifer Stone and Carmel Apicella and Fabrice Odefrey and Gierach, {Gretchen L.} and Jud, {Sebastian M.} and Katharina Heusinger and Beckmann, {Matthias W.} and Marina Pollan and Pablo Fernańdez-Navarro and Anna Gonzalez-Neira and Javier Benitez and {Van Gils}, {Carla H.} and Mari{\"e}tte Lokate and Onland-Moret, {N. Charlotte} and Peeters, {Petra H M} and Judith Brown and Jean Leyland and Varghese, {Jajini S.} and Easton, {Douglas F.} and Thompson, {Deborah J.} and Luben, {Robert N.} and Warren, {Ruth M L} and Wareham, {Nicholas J.} and Loos, {Ruth J F} and Khaw, {Kay Tee} and Giske Ursin and Eunjung Lee and Gayther, {Simon A.} and Ramus, {Susan J.} and Eeles, {Rosalind A.} and Leach, {Martin O.} and Gek Kwan-Lim and Couch, {Fergus J} and Giles, {Graham G.} and Laura Baglietto and Kavitha Krishnan and Southey, {Melissa C.} and {Le Marchand}, Loic and Kolonel, {Laurence N.} and Christy Woolcott and Gertraud Maskarinec and Haiman, {Christopher A.} and Kate Walker and Nichola Johnson and McCormack, {Valeria A.} and Margarethe Biong and Alnaes, {Grethe I G} and IngerTorhild Gram and Kristensen, {Vessela N.} and Br{\o}resen-Dale, {Anne Lise} and Sara Lindstrom̈ and Hankinson, {Susan E.} and Hunter, {David J.} and Andrulis, {Irene L.} and Knight, {Julia A.} and Boyd, {Norman F.} and Figuero, {Jonine D.} and Jolanta Lissowska and Ewa Wesolowska and Beata Peplonska and Agnieszka Bukowska and Edyta Reszka and JianJun Liu and Louise Eriksson and Kamila Czene and Tina Audley and Wu, {Anna H.} and Pankratz, {V. Shane} and Hopper, {John L.} and Isabel Dos-Santos-Silva",
year = "2012",
month = "7",
doi = "10.1158/1055-9965.EPI-12-0066",
language = "English (US)",
volume = "21",
pages = "1156--1166",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
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TY - JOUR

T1 - Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk

AU - Vachon, Celine M

AU - Scott, Christopher G.

AU - Fasching, Peter A.

AU - Hall, Per

AU - Tamimi, Rulla M.

AU - Li, Jingmei

AU - Stone, Jennifer

AU - Apicella, Carmel

AU - Odefrey, Fabrice

AU - Gierach, Gretchen L.

AU - Jud, Sebastian M.

AU - Heusinger, Katharina

AU - Beckmann, Matthias W.

AU - Pollan, Marina

AU - Fernańdez-Navarro, Pablo

AU - Gonzalez-Neira, Anna

AU - Benitez, Javier

AU - Van Gils, Carla H.

AU - Lokate, Mariëtte

AU - Onland-Moret, N. Charlotte

AU - Peeters, Petra H M

AU - Brown, Judith

AU - Leyland, Jean

AU - Varghese, Jajini S.

AU - Easton, Douglas F.

AU - Thompson, Deborah J.

AU - Luben, Robert N.

AU - Warren, Ruth M L

AU - Wareham, Nicholas J.

AU - Loos, Ruth J F

AU - Khaw, Kay Tee

AU - Ursin, Giske

AU - Lee, Eunjung

AU - Gayther, Simon A.

AU - Ramus, Susan J.

AU - Eeles, Rosalind A.

AU - Leach, Martin O.

AU - Kwan-Lim, Gek

AU - Couch, Fergus J

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - Krishnan, Kavitha

AU - Southey, Melissa C.

AU - Le Marchand, Loic

AU - Kolonel, Laurence N.

AU - Woolcott, Christy

AU - Maskarinec, Gertraud

AU - Haiman, Christopher A.

AU - Walker, Kate

AU - Johnson, Nichola

AU - McCormack, Valeria A.

AU - Biong, Margarethe

AU - Alnaes, Grethe I G

AU - Gram, IngerTorhild

AU - Kristensen, Vessela N.

AU - Brøresen-Dale, Anne Lise

AU - Lindstrom̈, Sara

AU - Hankinson, Susan E.

AU - Hunter, David J.

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Boyd, Norman F.

AU - Figuero, Jonine D.

AU - Lissowska, Jolanta

AU - Wesolowska, Ewa

AU - Peplonska, Beata

AU - Bukowska, Agnieszka

AU - Reszka, Edyta

AU - Liu, JianJun

AU - Eriksson, Louise

AU - Czene, Kamila

AU - Audley, Tina

AU - Wu, Anna H.

AU - Pankratz, V. Shane

AU - Hopper, John L.

AU - Dos-Santos-Silva, Isabel

PY - 2012/7

Y1 - 2012/7

N2 - Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures. Methods: We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and nondense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, BMI, and menopausal status. Results: Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (P = 0.00005) and adjusted percent density (P = 0.001), whereas the A-allele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (P = 0.003), but not with adjusted dense area (P = 0.07). Conclusion: We identified two common breast cancer susceptibility variants associated with mammographic measures of radiodense tissue in the breast gland. Impact: We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association.

AB - Background: Mammographic density adjusted for age and body mass index (BMI) is a heritable marker of breast cancer susceptibility. Little is known about the biologic mechanisms underlying the association between mammographic density and breast cancer risk. We examined whether common low-penetrance breast cancer susceptibility variants contribute to interindividual differences in mammographic density measures. Methods: We established an international consortium (DENSNP) of 19 studies from 10 countries, comprising 16,895 Caucasian women, to conduct a pooled cross-sectional analysis of common breast cancer susceptibility variants in 14 independent loci and mammographic density measures. Dense and nondense areas, and percent density, were measured using interactive-thresholding techniques. Mixed linear models were used to assess the association between genetic variants and the square roots of mammographic density measures adjusted for study, age, case status, BMI, and menopausal status. Results: Consistent with their breast cancer associations, the C-allele of rs3817198 in LSP1 was positively associated with both adjusted dense area (P = 0.00005) and adjusted percent density (P = 0.001), whereas the A-allele of rs10483813 in RAD51L1 was inversely associated with adjusted percent density (P = 0.003), but not with adjusted dense area (P = 0.07). Conclusion: We identified two common breast cancer susceptibility variants associated with mammographic measures of radiodense tissue in the breast gland. Impact: We examined the association of 14 established breast cancer susceptibility loci with mammographic density phenotypes within a large genetic consortium and identified two breast cancer susceptibility variants, LSP1-rs3817198 and RAD51L1-rs10483813, associated with mammographic measures and in the same direction as the breast cancer association.

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U2 - 10.1158/1055-9965.EPI-12-0066

DO - 10.1158/1055-9965.EPI-12-0066

M3 - Article

C2 - 22454379

AN - SCOPUS:84863580158

VL - 21

SP - 1156

EP - 1166

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 7

ER -