TY - JOUR
T1 - A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density
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
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
AU - Chang-Claude, Jenny
N1 - Publisher Copyright:
© 2015 Rudolph et al.
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 <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). Conclusions: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.
AB - 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 <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). Conclusions: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.
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U2 - 10.1186/s13058-015-0625-9
DO - 10.1186/s13058-015-0625-9
M3 - Article
C2 - 26275715
AN - SCOPUS:84938922712
SN - 1465-5411
VL - 17
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 110
ER -