A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density

Anja Rudolph, Peter A. Fasching, Sabine Behrens, Ursula Eilber, Manjeet K. Bolla, Qin Wang, Deborah Thompson, Kamila Czene, Judith S. Brand, Jingmei Li, Christopher Scott, V. Shane Pankratz, Kathleen R Brandt, Emily Hallberg, Janet E Olson, Adam Lee, Matthias W. Beckmann, Arif B. Ekici, Lothar Haeberle, Gertraud MaskarinecLoic Le Marchand, Fredrick Schumacher, Roger L. Milne, Julia A. Knight, Carmel Apicella, Melissa C. Southey, Miroslav K. Kapuscinski, John L. Hopper, Irene L. Andrulis, Graham G. Giles, Christopher A. Haiman, Kay Tee Khaw, Robert Luben, Per Hall, Paul D P Pharoah, Fergus J Couch, Douglas F. Easton, Isabel dos-Santos-Silva, Celine M Vachon, Jenny Chang-Claude

Research output: Contribution to journalArticle

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Abstract

Introduction: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. Methods: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. Results: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int int int SNP×MHT×case-status

Original languageEnglish (US)
Article number110
JournalBreast Cancer Research
Volume17
Issue number1
DOIs
StatePublished - Aug 16 2015

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Single Nucleotide Polymorphism
Hormones
Breast Neoplasms
Linear Models
Genome
Therapeutics
Cytochrome P-450 CYP1A2
Gene-Environment Interaction
Cytochrome P-450 CYP1A1
Mammography
Meta-Analysis
Breast Density
Health
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density. / Rudolph, Anja; Fasching, Peter A.; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Thompson, Deborah; Czene, Kamila; Brand, Judith S.; Li, Jingmei; Scott, Christopher; Pankratz, V. Shane; Brandt, Kathleen R; Hallberg, Emily; Olson, Janet E; Lee, Adam; Beckmann, Matthias W.; Ekici, Arif B.; Haeberle, Lothar; Maskarinec, Gertraud; Le Marchand, Loic; Schumacher, Fredrick; Milne, Roger L.; Knight, Julia A.; Apicella, Carmel; Southey, Melissa C.; Kapuscinski, Miroslav K.; Hopper, John L.; Andrulis, Irene L.; Giles, Graham G.; Haiman, Christopher A.; Khaw, Kay Tee; Luben, Robert; Hall, Per; Pharoah, Paul D P; Couch, Fergus J; Easton, Douglas F.; dos-Santos-Silva, Isabel; Vachon, Celine M; Chang-Claude, Jenny.

In: Breast Cancer Research, Vol. 17, No. 1, 110, 16.08.2015.

Research output: Contribution to journalArticle

Rudolph, A, Fasching, PA, Behrens, S, Eilber, U, Bolla, MK, Wang, Q, Thompson, D, Czene, K, Brand, JS, Li, J, Scott, C, Pankratz, VS, Brandt, KR, Hallberg, E, Olson, JE, Lee, A, Beckmann, MW, Ekici, AB, Haeberle, L, Maskarinec, G, Le Marchand, L, Schumacher, F, Milne, RL, Knight, JA, Apicella, C, Southey, MC, Kapuscinski, MK, Hopper, JL, Andrulis, IL, Giles, GG, Haiman, CA, Khaw, KT, Luben, R, Hall, P, Pharoah, PDP, Couch, FJ, Easton, DF, dos-Santos-Silva, I, Vachon, CM & Chang-Claude, J 2015, 'A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density', Breast Cancer Research, vol. 17, no. 1, 110. https://doi.org/10.1186/s13058-015-0625-9
Rudolph, Anja ; Fasching, Peter A. ; Behrens, Sabine ; Eilber, Ursula ; Bolla, Manjeet K. ; Wang, Qin ; Thompson, Deborah ; Czene, Kamila ; Brand, Judith S. ; Li, Jingmei ; Scott, Christopher ; Pankratz, V. Shane ; Brandt, Kathleen R ; Hallberg, Emily ; Olson, Janet E ; Lee, Adam ; Beckmann, Matthias W. ; Ekici, Arif B. ; Haeberle, Lothar ; Maskarinec, Gertraud ; Le Marchand, Loic ; Schumacher, Fredrick ; Milne, Roger L. ; Knight, Julia A. ; Apicella, Carmel ; Southey, Melissa C. ; Kapuscinski, Miroslav K. ; Hopper, John L. ; Andrulis, Irene L. ; Giles, Graham G. ; Haiman, Christopher A. ; Khaw, Kay Tee ; Luben, Robert ; Hall, Per ; Pharoah, Paul D P ; Couch, Fergus J ; Easton, Douglas F. ; dos-Santos-Silva, Isabel ; Vachon, Celine M ; Chang-Claude, Jenny. / A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density. In: Breast Cancer Research. 2015 ; Vol. 17, No. 1.
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abstract = "Introduction: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. Methods: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. Results: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int int int SNP×MHT×case-status",
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AU - Rudolph, Anja

AU - Fasching, Peter A.

AU - Behrens, Sabine

AU - Eilber, Ursula

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Thompson, Deborah

AU - Czene, Kamila

AU - Brand, Judith S.

AU - Li, Jingmei

AU - Scott, Christopher

AU - Pankratz, V. Shane

AU - Brandt, Kathleen R

AU - Hallberg, Emily

AU - Olson, Janet E

AU - Lee, Adam

AU - Beckmann, Matthias W.

AU - Ekici, Arif B.

AU - Haeberle, Lothar

AU - Maskarinec, Gertraud

AU - Le Marchand, Loic

AU - Schumacher, Fredrick

AU - Milne, Roger L.

AU - Knight, Julia A.

AU - Apicella, Carmel

AU - Southey, Melissa C.

AU - Kapuscinski, Miroslav K.

AU - Hopper, John L.

AU - Andrulis, Irene L.

AU - Giles, Graham G.

AU - Haiman, Christopher A.

AU - Khaw, Kay Tee

AU - Luben, Robert

AU - Hall, Per

AU - Pharoah, Paul D P

AU - Couch, Fergus J

AU - Easton, Douglas F.

AU - dos-Santos-Silva, Isabel

AU - Vachon, Celine M

AU - Chang-Claude, Jenny

PY - 2015/8/16

Y1 - 2015/8/16

N2 - Introduction: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. Methods: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. Results: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int int int SNP×MHT×case-status

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