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

被引：16

作者：

Rudolph, Anja ^{[1
]}

Fasching, Peter A. ^{[2
,3
]}

Behrens, Sabine ^{[1
]}

Eilber, Ursula ^{[1
]}

Bolla, Manjeet K. ^{[4
]}

Wang, Qin ^{[4
]}

Thompson, Deborah ^{[4
]}

Czene, Kamila ^{[5
]}

Brand, Judith S. ^{[5
]}

Li, Jingmei ^{[5
]}

Scott, Christopher ^{[6
]}

Pankratz, V. Shane ^{[6
]}

Brandt, Kathleen ^{[7
]}

Hallberg, Emily ^{[8
]}

Olson, Janet E. ^{[8
]}

Lee, Adam ^{[9
]}

Beckmann, Matthias W. ^{[2
]}

Ekici, Arif B. ^{[10
]}

Haeberle, Lothar ^{[2
]}

Maskarinec, Gertraud ^{[11
]}

Le Marchand, Loic ^{[11
]}

Schumacher, Fredrick ^{[12
]}

Milne, Roger L. ^{[13
,14
]}

Knight, Julia A. ^{[15
,16
]}

Apicella, Carmel ^{[14
]}

Southey, Melissa C. ^{[17
]}

Kapuscinski, Miroslav K. ^{[14
]}

Hopper, John L. ^{[14
]}

Andrulis, Irene L. ^{[18
,19
]}

Giles, Graham G. ^{[13
,14
]}

Haiman, Christopher A. ^{[12
]}

Khaw, Kay-Tee ^{[20
]}

Luben, Robert ^{[21
]}

Hall, Per ^{[5
]}

Pharoah, Paul D. P. ^{[4
,22
]}

Couch, Fergus J. ^{[23
]}

Easton, Douglas F. ^{[4
,22
]}

dos-Santos-Silva, Isabel ^{[24
]}

Vachon, Celine ^{[8
]}

Chang-Claude, Jenny ^{[1
]}

机构：

[1] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[2] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Obstet & Gynaecol, Comprehens Canc Ctr Erlangen EMN, D-91054 Erlangen, Germany

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA

[4] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England

[5] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[6] Mayo Clin, Div Biostat, Rochester, MN USA

[7] Mayo Clin, Dept Radiol, Rochester, MN USA

[8] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[9] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA

[10] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Inst Human Genet, D-91054 Erlangen, Germany

[11] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA

[12] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

[13] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[14] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia

[15] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada

[16] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada

[17] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

[18] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada

[19] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[20] Univ Cambridge, MRC Ctr Nutrit Epidemiol Canc Prevent & Survival, Cambridge, England

[21] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England

[22] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[23] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[24] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England

来源：

BREAST CANCER RESEARCH | 2015年 / 17卷

基金：

美国国家卫生研究院; 加拿大健康研究院; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; BREAST-CANCER RISK; PHOSPHOLIPASE C-GAMMA-2; SUSCEPTIBILITY VARIANTS; POSTMENOPAUSAL WOMEN; PROLACTIN LEVELS; POLYMORPHISMS; ESTROGEN; TAMOXIFEN; LOCI;

D O I：

10.1186/s13058-015-0625-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 SNPxMHTxcase-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.

引用

页数：12

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