Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
Year: 2022
Type: article
Study design: Observational Study
Abstract: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10 –8 as genome-wide significant, and p-values < 1 × 10 –5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 10 5 . The strongest evidence was found for rs4674019 (p-value = 2.27 × 10 –7 ), which showed genome-wide significant interaction (p-value = 3.8 × 10 –8 ) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen–progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.
Source: Scientific Reports
Authors: Xiaoliang Wang, Pooja Middha Kapoor, Paul L. Auer, Joe Dennis, Alison M. Dunning, Qin Wang, Michael Lush, Kyriaki Michailidou, Manjeet K. Bolla, Kristan J. Aronson, Rachel A. Murphy, Angela Brooks-Wilson, Derrick G. Lee, Emilie Cordina-Duverger, Pascal Guénel, Thérèse Truong, Claire Mulot, Lauren R. Teras, Alpa V. Patel, Laure Dossus, Rudolf Kaaks, Reiner Hoppe, Wing-Yee Lo, Thomas Brüning, Ute Hamann, Kamila Czene, Marike Gabrielson, Per Hall, Mikael Eriksson, Audrey Jung, Heiko Becher, Fergus J. Couch, Nicole L. Larson, Janet E. Olson, Kathryn J. Ruddy, Graham G. Giles, Robert J. MacInnis, Melissa C. Southey, Loic Le Marchand, Lynne R. Wilkens, Christopher A. Haiman, Håkan Olsson, Annelie Augustinsson, Ute Krüger, Philippe Wagner, Christopher Scott, Stacey J. Winham, Celine M. Vachon, Charles M. Perou, Andrew F. Olshan, Melissa A. Troester, David J. Hunter, Heather A. Eliassen, Rulla M. Tamimi, Kristen Brantley, Irene L. Andrulis, Jonine Figueroa, Stephen J. Chanock, Thomas U. Ahearn, Montserrat García-Closas, Gareth D. Evans, William G. Newman, Elke M. van Veen, Anthony Howell, Alicja Wolk, Niclas Håkansson, Hoda Anton-Culver, Argyrios Ziogas, Michael E. Jones, Nick Orr, Minouk J. Schoemaker, Anthony J. Swerdlow, Cari M. Kitahara, Martha Linet, Ross L. Prentice, Douglas F. Easton, Roger L. Milne, Peter Kraft, Jenny Chang-Claude, Sara Lindström
Institutions: University of Washington, Fred Hutch Cancer Center, German Cancer Research Center, Heidelberg University, Medical College of Wisconsin, Medical College of Wisconsin Cancer Center, University of Cambridge, The Cyprus Institute of Neurology & Genetics - Postgraduate Education, Cyprus Institute of Neurology and Genetics, Queen's University, BC Cancer Agency, University of British Columbia, Simon Fraser University, St. Francis Xavier University, Inserm, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Paris-Sorbonne University, American Cancer Society, Centre international de recherche sur le cancer, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Institute for Prevention and Occupational Medicine, Karolinska Institutet, Stockholm South General Hospital, University Medical Center Hamburg-Eppendorf, Mayo Clinic, The University of Melbourne, Cancer Council Victoria, Monash Health, Monash University, University of Hawaii Cancer Center, University of Southern California, Lund University, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Harvard University, University of Oxford, Brigham and Women's Hospital, Weill Cornell Medicine, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, National Institutes of Health, Edinburgh Cancer Research, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University of Edinburgh, Manchester Academic Health Science Centre, University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Uppsala University, University of California, Irvine, Institute of Cancer Research, Queen's University Belfast, University Cancer Center Hamburg
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,190
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Susan G. Komen for the Cure, Breast Cancer Research Foundation, Ovarian Cancer Research Fund, World Health Organization, Division of Cancer Prevention, National Cancer Institute, McGill University, Deutsches Krebsforschungszentrum, Genome Canada, David F. and Margaret T. Grohne Family Foundation, Swedish Cancer Foundation, Génome Québec, Fondation du cancer du sein du Québec, Lon V. Smith Foundation, Government of Canada, Cancer Research UK, National Institute for Health and Care Research, Imperial College London, European Commission, Agency for Science, Technology and Research, Robert Bosch Stiftung, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Eberhard Karls Universität Tübingen, Bundesministerium für Bildung und Forschung, Cancerfonden, Ministerio de Economía y Competitividad, Deutsche Gesetzliche Unfallversicherung, Ligue Contre le Cancer, Vetenskapsrådet, Fondation de France, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut National Du Cancer, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Deutschen Konsortium für Translationale Krebsforschung, Bundesministerium für Bildung, Wissenschaft und Forschung, National Institutes of Health, Centers for Disease Control and Prevention, Canadian Institutes of Health Research, Medical Research Council, World Cancer Research Fund, National Health and Medical Research Council, Cancer Council Victoria, Instituto de Salud Carlos III, Programme Grants for Applied Research, School of Public Health, Imperial College London, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Environmental Health Sciences, Division of Cancer Epidemiology and Genetics, National Cancer Institute
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G4715308887, G4719203780, Risk and penetrance of mutations from breast cancer testing panels., G472201624, G4722955430, G4727172548, G4730585134, G473154824, G4731890028, G4734229721, G4744540905, G4745409881, G4752555454, G4756843171, G4758570167, G4762271477, G476489484, G4768633597, G4773629080, G4779161500, G4786373955, G480120991, G4811780622, G4812243687, G4814591014, G4817291204, G4819905405, G4822262273, G4830796271, G4844208673, G4844702211, G4849618962, G4849911869, G4852749512, G4854431980, G4857061935, G4859161029, G4861632975, G4868136889, G4869733621, G4870598717, G4877949309, G4879747564, G4881976733, G4887716027, G4890525657, G4893182399, G4893741037, G4896801626, G4897344887, G4902239870, G490534113, G4907478063, G4914513279, G4915529853, G4920666861, G4920900562, G4923733781, G4930480761, G493358262, G4940192625, G494830712, G4950660695, G495186059, G4953108759, G4960961974, G4963032258, G4963598836, G4968615377, G4968824801, G4975249626, G4978378898, G4991056325, G4991908250, G4995407577, G5001329134, G500192141, G5004963360, G5009853252, G5015396337, G50174683, G5019474394, G5021666829, G5022167271, G502420549, G5025616412, G5026227935, G5026815028, G5035028408, G5035440390, G504460986, G5045046497, G5052768465, G5054695680, G5058997197, G5069802979, G5072279207, G5072770487, G5076849354, G507980549, G508357843, G5098909591, G5099964288, G5113804109, G5123028305, G5125924262, G5140140656, G514090287, G5151594043, G5162528566, G5177883595, G5178632369, G5181373253, G5182528219, G5192555790, G519753990, G5197845165, G5198239130, G5200911854, G5206874578, G5208162737, G5209556947, G521055268, G5211583990, G5218421771, G5218858701, G5259089724, G5266347122, Core Infrastructure and Methodological Research for Cancer Epidemiology Cohorts, G5272917877, G5273521901, G5284145241, G529103831, G5294110089, G5298817638, G5299669052, G5301809168, G5304242060, G5305809410, G5309499537, G531047512, G5319846138, G5321429115, G5323556995, G5323685217, G532380461, G5330159664, G533090119, G5338223732, G5343409947, G5352577715, G5355554231, G535679862, G5357465865, G5360760185, G5361256448, G5371109736, G5373760811, G5375387566, G5376615654, G5392603663, G5395379871, G5400679422, G5401762342, G5403009340, G5403268578, G54047005, G5404725132, G5407607757, G5408124265, G5409203474, G5415213071, G5420159238, G542302685, G5432187923, G5433877598, G5434589445, G5435148814, G543680480, G5437004515, G5438742080, Life Course Cancer Epidemiology Cohort in Women, G5452358205, G5452432248, G5462907487, G5468790521, G546882899, G547275475, G5475326692, G5483300039, G5486405922, G5491114930, G5496469482, G5498658778, G5498801985, G5515866484, G5523118394, G5527714048, G5530303955, Identifying Genes for Mammographic Breast Density, G5547620395, G5549244980, G5565827463, G5566577447, G5568856568, G5573301997, G5577027992, G558017500, G558159996, G5583696067, G5585565996, G5588039662, G5592897315, G5600012445, G5604884852, G5605482045, G5621875644, G5623755075, G5624510383, G5637269007, G563851066, G564060976, G5646482517, G5647578397, G5649857278, G5654214539, G5655665560, G5666410983, G5667548518, G5671288941, G5671701345, G567420851, G5677485672, G5678309574, G5678951655, G5691136419, G5692258984, G5695285961, G570380659, G5705106108, G5706956023, G5706984478, G5723470122, G5738488509, G5742312296, G5748211427, G5749450092, G5750542632, G5756664977, G5760907765, G5768262392, G5768527752, G5769702817, G5772013900, G5780361171, G5789635941, G5794032522, G5800068108, G5805734732, G5810475390, G581425120, G5824370075, G5826812399, G5831092029, G5834695558, G5838842695, G5842033281, G5842535854, G5844522323, G584725795, G5849396529, G5850682332, G5851393153, G5851461211, Functional characterization of polycystins, G586064783, G5864148181, G5865683244, G5873433241, G5879141835, G588939897, G5897142711, G5901467367, G5906745929, G5916056927, G5930124869, G5932286462, G5934054167, G5952534786, G5955236189, G5959494706, G5990830295, G5991032111, G5991087437, G5992821780, G5994485482, G5999821407, G5999899560, G6004621315, G6005669683, G6006834435, G601295959, G6022976577, G6023365166, G6025062416, G6025337639, G602992300, G6035964259, G6040519212, G6041192005, G6046728338, G60573655, G6058533437, G6069018159, G6078392164, G6079786710, G6080346254, G6081138880, G6085534252, G6091705888, G6095809094, G6097013043, G6100033090, G6112083080, G6115934749, G6117182389, G6117895294, G611851238, G6120192074, G6124735236, G6136237335, G6137013498, G6140938529, G6142457952, G6144205333, G6144582627, G614814196, G6150659847, G6150950394, G6152496355, NIHR Senior Investigator Award, G6160354019, G616297784, G6171224667, G6177794165, G6180318878, G6182626225, G6187643630, G6191607766, G6195211026, G619791618, G619901973, G6200764915, G6204131256, G6211918717, G621290712, G622191773, G6228179203, G6229591247, G6231561224, G62421433, G62519578, G6254892548, G6256940186, G627137762, G6272687058, G6272766454, G6294496840, G6294906247, Automated Density Measures for Estimating Breast Cancer Risk and Therapy Response, G6304544667, G6305665937, G6306456061, G6309272015, G6341818539, G6343431347, G6346811214, G63610454, G6362187187, G6366270716, G6370616640, G6370857267, G6372256998, G6376423330, G6378106617, G6379995370, G6388635936, G6392809671, G6394719143, G6402876381, G6413938271, G642724699, G6433750405, G6437615964, G6443441345, G6443445030, G6445710272, G6453123296, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G6461078106, G6467036301, G6468858423, G6471584761, G6473583094, G6476120666, G6476783403, G6479126130, G6480339625, G6481099357, G6486574503, G6490068802, G649375150, G6494288067, G6498720199, G6505221676, G6516220988, G6535168135, G6537191622, G654016345, G6541023505, G6546742586, G6552302344, G6557157180, G6558636245, G655929293, G6566148188, G6581613071, G6584347414, G6585166083, G6591690649, G6594529311, G6596498490, G6600658725, G6604307332, G6608264682, G6610343406, G6613900531, G6615319394, G6616185778, G6621265754, G6628312008, G663052312, G6631754812, G663334079, G6639643895, G6649104264, G6654466364, G6656156659, G6660897383, G6672799866, G6675395858, G667666382, G6677716848, G6682693437, G668499276, Epidemiology of Chronic Disease, Health Interventions and DNA Studies, G6698438818, G6701267922, G6704689538, G6716354403, G6719391877, G6720501597, G6727411954, G672981, G6741060998, G674394642, G6744381054, G6744405293, G6747998312, G6750698717, G6761260408, G6766485657, G6770964173, G6773606939, G6776306215, G6780254327, G6785688949, G6792423459, G6808693096, G68091798, G6811600868, G6812580533, G6814299652, G6817868630, G6822933559, G6838805842, G683931929, G6841192967, G6850174406, G6858204494, G6863598602, G6866608100, G6871046858, G6872533491, G6878857939, G6885153221, G6887972972, G6888779489, G6902192277, G6915014223, G6917856592, G6923329853, G6929791624, G6934009282, G6935796278, G6939370713, G6945661269, G6954567555, G6957475921, G6957738817, G6967911674, G697471701, G6977685539, G6985834368, G6990177591, G6990806275, G700146251, G7006486244, G7007900328, The protective effects of the flavonoid quercetin against glial cell apoptosis, G7014846622, G7017064073, G7025046877, G7025781913, G7030639063, G7036369858, G7037647046, G7038833263, G7042089715, G7043007222, Risk factors for breast cancer molecular subtypes, G704544610, G7045847803, G7051714513, G7053841699, G7055847034, G705967134, G7059787294, G7061792830, G7070449706, G707346186, G7077480220, G708414388, G7085323860, G708657111, G7088314342, G7095192201, G7110999019, G7114940062, G712569388, G7129568825, G7131564045, G7133737134, G7140941202, G7152405674, G7165037524, G7172319646, G7172402457, G7173888283, G7174179526, G7180840450, G7181378667, G7194594628, G7199237069, G7199491060, G7208330911, G7210319196, G7212473182, G7212759837, G7213586829, G7223051280, G7235675205, G7238546996, G723878899, G7241791320, G7242219286, G7243233673, G7258059550, G7260656849, G7264367372, G7277877115, G7280168628, G7283889457, G7284407195, G7286015836, G7287381913, Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis, G7292031277, G7296172712, G7307876031, G7310063491, G7321660720, G7336324573, G7339350182, G734127494, G734227365, G734892404, G7356174861, G7356264847, G7357522587, G7368561066, G7371122787, G7372524322, G7374748916, G7375233134, G7375939797, G7378364093, G7382280645, G7383316951, G7393258936, G7400227903, G7402670107, G7402923325, G7407369017, G7408643460, G7410254275, G7426181285, G7427462524, G7428685430, G7430234978, G7432903467, G7444664598, G7446181628, G7447125227, G7459520778, G7460782533, G7464850895, G7469845195, G7473445654, G7483126157, G7490826781, G7493026, G749501992, G7500783097, G7501896692, G7502883741, G7503396464, G7505214508, G7505384502, G7510707455, G751661945, G7524210594, G7527307771, G7531233806, G7543979321, G7550424651, G7550995080, G7553674075, G7556704279, G7557895011, G7559120220, G7561683782, G7564442485, G7564647349, G757021927, G7570543806, G7570682278, G7573107169, G7579085979, G7590654100, G7596519453, G7601185679, G7603965662, G7608403635, G7615341341, G7618966743, G7625083360, G7629529491, G7631676291, G7645511635, G7646326732, G7650865334, G7652198732, G7652900232, G7659260347, G7660541068, G7663583697, G7667237, G7667648416, G7672802699, BRCA1 and BRCA2 missense mutations and breast cancer risk, G7677770324, G7680442207, G7683724993, G7684595986, G7689728446, G7695043024, G7698680401, G7700294005, G7704992235, G7706179373, G7714640921, G7719499675, G7719802095, G7720439865, G7720878368, G7724260473, G7724311201, G7730201318, G77340863, G7735960074, G774073435, G7743229171, G7745959692, G7750109879, G7750343902, G775647737, G7759275668, G7785285623, G7792675715, G7802461500, G7809591785, G7818112964, G7820459769, G7821778997, G7822233700, G7825718492, G7837954180, G7838862750, G784369578, G7845742348, G7850585328, G7863779903, G7865343161, G7869444022, G7875552478, G7878140493, G7880927129, G7885991059, G7888071330, G7891086452, G7891939106, Identifying and validating novel susceptibility genes for breast cancer, G7899396062, G790382466, G7909060642, G7910996903, G7912380902, G7922711448, G792556191, G7926178030, G7927074216, G7931532932, G7931980960, G7935657002, G7941428382, G7942264290, G7946625978, G7949376443, G7959980841, G7967151832, G7970295385, G7975826117, G7978929429, G797945619, G798245942, G7983258154, G7987655622, G7992389077, G7993655663, G7998126057, G8001103002, G8002102998, G8008039535, G8009692560, G8012362051, G8028536217, G8028941638, G8032710450, G803995699, G8047153950, G8047235752, G8048544268, G8050896463, G8057311431, G8061499453, G8064793800, G8068543626, G8079645633, G8080314480, G8086612828, G8087462753, G8091257830, G8092145710, G8093364034, G8095698379, G809773228, G812132760, G8123808567, G8143219610, G8147327976, G8155739244, G8157532935, G8168835903, G8170394619, G8181826844, G8184178841, G8184739039, G8187259655, G8203727749, G8209208257, G8211152118, G821207138, G821701785, G8217849301, G8220788639, G8230221726, G8231657851, G8236204260, G8252467741, G8254542482, G8266408936, G8276210270, G827920996, G8280143671, G8280464780, G8283179918, G8286131369, G8288525579, G8290722994, GENETIC MODIFIERS OF OVARIAN CANCER, G829717837, G8302722731, G8304451412, G8313202159, G8325934978, G8336111703, G8337188992, G8343740385, G8344269847, G8354808054, G83581208, G8360006069, G8366320228, G8371914649, G8377080268, G8387986889, G8392881711, Collaborative Oncological Gene-environment Study, G8413675353, G8416541982, G842131773, G8422646305, G8429796442, G8435125888, G8436967239, G84425124, G8446309498, G8450529846, G8450775414, G8451314362, G8451975646, G845286615, G8453491360, G8454631840, G846045368, G8463943344, G8464468401, G8470841720, G847461785, G848244660, G8492020821, G8492627253, G8494664603, G8503305451, G8503433390, G8505307412, G8511115326, G8515565311, G8523447525, G8534518164, G8535868846, G8536616440, G8537030507, G8537738258, G854192367, G8544198431, G8551454767, G855456547, G8561484738, G856283587, G8575958574, G8593847461, G8600969490, G8605664644, G8626150033, G8630982842, G8647861985, G8651849717, G8652899496, G8653240953, G8655401850, G8656021485, G8656305928, G8658451913, G8658736651, G8668082143, G8670783839, G8683288336, G8695884017, G8702800630, G8703060161, G8708995835, G8717574252, G8718460262, G8718893896, G8725735482, G872696599, G8731890904, G873407380, G8767780462, G8773809704, G8774728694, G8781426925, G8782320974, G8787944841, G8790823546, G8791870606, G8792299897, G8793360539, G8797697851, G880611044, G8808853864, G88130622, G8818365897, G8820111440, G8834430567, G8837605162, G8848440661, G8851220955, G8853615787, G8854317076, G885693336, G8864782299, G8867453513, G8883100996, G889552446, G8895704725, G8901774384, G8908128081, G8916941414, G8918134885, G8919560141, G8924490982, G8932870499, G8942463566, G8943998091, G895030187, G8952818352, G8953328912, G8954186739, G8954187506, G8954419909, G895493773, G8955026464, G8959936493, G8960002408, G8961487230, G8963950986, G8964342090, G897137893, G8974852769, G8976871661, G8978728421, G8983892756, G8987248239, G8993121883, G8999001090, G9000017222, G9000023510, G9000025899, G9000040826, G9000045919, G9000048109, G9000055689, G9000058679, G9000081378, G9000084571, G9000099730, G9000101281, G9000114967, G9000117861, G9000118332, G9000124663, G9000127596, G9000135043, G9000157792, G9000165800, G9000167727, G9000175716, G9000176900, G9000190097, G9000193140, G9000194218, G9000200580, G9000214939, G9000216949, G9000265968, G9000272137, G9000273748, G9000282203, G9000286278, G9000291106, G9000311251, G9000311646, Mayo Clinic Comprehensive Cancer Center Support Grant, G901453306, G901954130, G90415124, G907415430, G90783244, G915296990, G922049100, EXC 2180: Individualisierung von Tumortherapien durch molekulare Bildgebung und funktionelle Identifizierung therapeutischer Zielstrukturen (iFIT), G943973600, G952755447, G966753049, G980830052, G986797651, G993886882, G99598583, G99680112
OpenAlex ID: W4225499852