Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.
Identifieur interne : 003A95 ( PubMed/Corpus ); précédent : 003A94; suivant : 003A96Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.
Auteurs : Anja Rudolph ; Rebecca Hein ; Sara Lindström ; Lars Beckmann ; Sabine Behrens ; Jianjun Liu ; Hugues Aschard ; Manjeet K. Bolla ; Jean Wang ; Thérèse Truong ; Emilie Cordina-Duverger ; Florence Menegaux ; Thomas Brüning ; Volker Harth ; Gianluca Severi ; Laura Baglietto ; Melissa Southey ; Stephen J. Chanock ; Jolanta Lissowska ; Jonine D. Figueroa ; Mikael Eriksson ; Keith Humpreys ; Hatef Darabi ; Janet E. Olson ; Kristen N. Stevens ; Celine M. Vachon ; Julia A. Knight ; Gord Glendon ; Anna Marie Mulligan ; Alan Ashworth ; Nicholas Orr ; Minouk Schoemaker ; Penny M. Webb ; Pascal Guénel ; Hiltrud Brauch ; Graham Giles ; Montserrat García-Closas ; Kamila Czene ; Georgia Chenevix-Trench ; Fergus J. Couch ; Irene L. Andrulis ; Anthony Swerdlow ; David J. Hunter ; Dieter Flesch-Janys ; Douglas F. Easton ; Per Hall ; Heli Nevanlinna ; Peter Kraft ; Jenny Chang-ClaudeSource :
- Endocrine-related cancer [ 1479-6821 ] ; 2013.
English descriptors
- KwdEn :
- Biomarkers, Tumor (genetics), Breast Neoplasms (etiology), Carcinoma, Lobular (etiology), Case-Control Studies, Female, Genes, Modifier (genetics), Genetic Predisposition to Disease, Genome-Wide Association Study, Hormone Replacement Therapy (adverse effects), Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide (genetics), Prognosis, Risk Factors.
- MESH :
- chemical , genetics : Biomarkers, Tumor.
- adverse effects : Hormone Replacement Therapy.
- etiology : Breast Neoplasms, Carcinoma, Lobular.
- genetics : Genes, Modifier, Polymorphism, Single Nucleotide.
- Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Prognosis, Risk Factors.
Abstract
Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.
DOI: 10.1530/ERC-13-0349
PubMed: 24080446
Links to Exploration step
pubmed:24080446Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.</title><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Foundation for Quality and Efficiency in Health Care (IQWIG), Cologne, Germany Human Genetics, Genome Institute of Singapore, Singapore, Singapore Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK INSERM (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France Unité Mixte de Recherche Scientifique (UMRS) 1018, University Paris-Sud, Villejuif, France Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany Institute for Occupational Medicine and Maritime Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany Institute of Pathology, University of Bonn, Bonn, Germany Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia Division of Cancer Epidemiology and Genetics, N</nlm:affiliation></affiliation></author><author><name sortKey="Hein, Rebecca" sort="Hein, Rebecca" uniqKey="Hein R" first="Rebecca" last="Hein">Rebecca Hein</name></author><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name></author><author><name sortKey="Beckmann, Lars" sort="Beckmann, Lars" uniqKey="Beckmann L" first="Lars" last="Beckmann">Lars Beckmann</name></author><author><name sortKey="Behrens, Sabine" sort="Behrens, Sabine" uniqKey="Behrens S" first="Sabine" last="Behrens">Sabine Behrens</name></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name></author><author><name sortKey="Aschard, Hugues" sort="Aschard, Hugues" uniqKey="Aschard H" first="Hugues" last="Aschard">Hugues Aschard</name></author><author><name sortKey="Bolla, Manjeet K" sort="Bolla, Manjeet K" uniqKey="Bolla M" first="Manjeet K" last="Bolla">Manjeet K. Bolla</name></author><author><name sortKey="Wang, Jean" sort="Wang, Jean" uniqKey="Wang J" first="Jean" last="Wang">Jean Wang</name></author><author><name sortKey="Truong, Therese" sort="Truong, Therese" uniqKey="Truong T" first="Thérèse" last="Truong">Thérèse Truong</name></author><author><name sortKey="Cordina Duverger, Emilie" sort="Cordina Duverger, Emilie" uniqKey="Cordina Duverger E" first="Emilie" last="Cordina-Duverger">Emilie Cordina-Duverger</name></author><author><name sortKey="Menegaux, Florence" sort="Menegaux, Florence" uniqKey="Menegaux F" first="Florence" last="Menegaux">Florence Menegaux</name></author><author><name sortKey="Bruning, Thomas" sort="Bruning, Thomas" uniqKey="Bruning T" first="Thomas" last="Brüning">Thomas Brüning</name></author><author><name sortKey="Harth, Volker" sort="Harth, Volker" uniqKey="Harth V" first="Volker" last="Harth">Volker Harth</name></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name></author><author><name sortKey="Southey, Melissa" sort="Southey, Melissa" uniqKey="Southey M" first="Melissa" last="Southey">Melissa Southey</name></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J" last="Chanock">Stephen J. Chanock</name></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name></author><author><name sortKey="Figueroa, Jonine D" sort="Figueroa, Jonine D" uniqKey="Figueroa J" first="Jonine D" last="Figueroa">Jonine D. Figueroa</name></author><author><name sortKey="Eriksson, Mikael" sort="Eriksson, Mikael" uniqKey="Eriksson M" first="Mikael" last="Eriksson">Mikael Eriksson</name></author><author><name sortKey="Humpreys, Keith" sort="Humpreys, Keith" uniqKey="Humpreys K" first="Keith" last="Humpreys">Keith Humpreys</name></author><author><name sortKey="Darabi, Hatef" sort="Darabi, Hatef" uniqKey="Darabi H" first="Hatef" last="Darabi">Hatef Darabi</name></author><author><name sortKey="Olson, Janet E" sort="Olson, Janet E" uniqKey="Olson J" first="Janet E" last="Olson">Janet E. Olson</name></author><author><name sortKey="Stevens, Kristen N" sort="Stevens, Kristen N" uniqKey="Stevens K" first="Kristen N" last="Stevens">Kristen N. Stevens</name></author><author><name sortKey="Vachon, Celine M" sort="Vachon, Celine M" uniqKey="Vachon C" first="Celine M" last="Vachon">Celine M. Vachon</name></author><author><name sortKey="Knight, Julia A" sort="Knight, Julia A" uniqKey="Knight J" first="Julia A" last="Knight">Julia A. Knight</name></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name></author><author><name sortKey="Mulligan, Anna Marie" sort="Mulligan, Anna Marie" uniqKey="Mulligan A" first="Anna Marie" last="Mulligan">Anna Marie Mulligan</name></author><author><name sortKey="Ashworth, Alan" sort="Ashworth, Alan" uniqKey="Ashworth A" first="Alan" last="Ashworth">Alan Ashworth</name></author><author><name sortKey="Orr, Nicholas" sort="Orr, Nicholas" uniqKey="Orr N" first="Nicholas" last="Orr">Nicholas Orr</name></author><author><name sortKey="Schoemaker, Minouk" sort="Schoemaker, Minouk" uniqKey="Schoemaker M" first="Minouk" last="Schoemaker">Minouk Schoemaker</name></author><author><name sortKey="Webb, Penny M" sort="Webb, Penny M" uniqKey="Webb P" first="Penny M" last="Webb">Penny M. Webb</name></author><author><name sortKey="Guenel, Pascal" sort="Guenel, Pascal" uniqKey="Guenel P" first="Pascal" last="Guénel">Pascal Guénel</name></author><author><name sortKey="Brauch, Hiltrud" sort="Brauch, Hiltrud" uniqKey="Brauch H" first="Hiltrud" last="Brauch">Hiltrud Brauch</name></author><author><name sortKey="Giles, Graham" sort="Giles, Graham" uniqKey="Giles G" first="Graham" last="Giles">Graham Giles</name></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="García-Closas">Montserrat García-Closas</name></author><author><name sortKey="Czene, Kamila" sort="Czene, Kamila" uniqKey="Czene K" first="Kamila" last="Czene">Kamila Czene</name></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J" last="Couch">Fergus J. Couch</name></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L" last="Andrulis">Irene L. Andrulis</name></author><author><name sortKey="Swerdlow, Anthony" sort="Swerdlow, Anthony" uniqKey="Swerdlow A" first="Anthony" last="Swerdlow">Anthony Swerdlow</name></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J" last="Hunter">David J. Hunter</name></author><author><name sortKey="Flesch Janys, Dieter" sort="Flesch Janys, Dieter" uniqKey="Flesch Janys D" first="Dieter" last="Flesch-Janys">Dieter Flesch-Janys</name></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:24080446</idno><idno type="pmid">24080446</idno><idno type="doi">10.1530/ERC-13-0349</idno><idno type="wicri:Area/PubMed/Corpus">003A95</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003A95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.</title><author><name sortKey="Rudolph, Anja" sort="Rudolph, Anja" uniqKey="Rudolph A" first="Anja" last="Rudolph">Anja Rudolph</name><affiliation><nlm:affiliation>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Foundation for Quality and Efficiency in Health Care (IQWIG), Cologne, Germany Human Genetics, Genome Institute of Singapore, Singapore, Singapore Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK INSERM (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France Unité Mixte de Recherche Scientifique (UMRS) 1018, University Paris-Sud, Villejuif, France Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany Institute for Occupational Medicine and Maritime Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany Institute of Pathology, University of Bonn, Bonn, Germany Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia Division of Cancer Epidemiology and Genetics, N</nlm:affiliation></affiliation></author><author><name sortKey="Hein, Rebecca" sort="Hein, Rebecca" uniqKey="Hein R" first="Rebecca" last="Hein">Rebecca Hein</name></author><author><name sortKey="Lindstrom, Sara" sort="Lindstrom, Sara" uniqKey="Lindstrom S" first="Sara" last="Lindström">Sara Lindström</name></author><author><name sortKey="Beckmann, Lars" sort="Beckmann, Lars" uniqKey="Beckmann L" first="Lars" last="Beckmann">Lars Beckmann</name></author><author><name sortKey="Behrens, Sabine" sort="Behrens, Sabine" uniqKey="Behrens S" first="Sabine" last="Behrens">Sabine Behrens</name></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name></author><author><name sortKey="Aschard, Hugues" sort="Aschard, Hugues" uniqKey="Aschard H" first="Hugues" last="Aschard">Hugues Aschard</name></author><author><name sortKey="Bolla, Manjeet K" sort="Bolla, Manjeet K" uniqKey="Bolla M" first="Manjeet K" last="Bolla">Manjeet K. Bolla</name></author><author><name sortKey="Wang, Jean" sort="Wang, Jean" uniqKey="Wang J" first="Jean" last="Wang">Jean Wang</name></author><author><name sortKey="Truong, Therese" sort="Truong, Therese" uniqKey="Truong T" first="Thérèse" last="Truong">Thérèse Truong</name></author><author><name sortKey="Cordina Duverger, Emilie" sort="Cordina Duverger, Emilie" uniqKey="Cordina Duverger E" first="Emilie" last="Cordina-Duverger">Emilie Cordina-Duverger</name></author><author><name sortKey="Menegaux, Florence" sort="Menegaux, Florence" uniqKey="Menegaux F" first="Florence" last="Menegaux">Florence Menegaux</name></author><author><name sortKey="Bruning, Thomas" sort="Bruning, Thomas" uniqKey="Bruning T" first="Thomas" last="Brüning">Thomas Brüning</name></author><author><name sortKey="Harth, Volker" sort="Harth, Volker" uniqKey="Harth V" first="Volker" last="Harth">Volker Harth</name></author><author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name></author><author><name sortKey="Baglietto, Laura" sort="Baglietto, Laura" uniqKey="Baglietto L" first="Laura" last="Baglietto">Laura Baglietto</name></author><author><name sortKey="Southey, Melissa" sort="Southey, Melissa" uniqKey="Southey M" first="Melissa" last="Southey">Melissa Southey</name></author><author><name sortKey="Chanock, Stephen J" sort="Chanock, Stephen J" uniqKey="Chanock S" first="Stephen J" last="Chanock">Stephen J. Chanock</name></author><author><name sortKey="Lissowska, Jolanta" sort="Lissowska, Jolanta" uniqKey="Lissowska J" first="Jolanta" last="Lissowska">Jolanta Lissowska</name></author><author><name sortKey="Figueroa, Jonine D" sort="Figueroa, Jonine D" uniqKey="Figueroa J" first="Jonine D" last="Figueroa">Jonine D. Figueroa</name></author><author><name sortKey="Eriksson, Mikael" sort="Eriksson, Mikael" uniqKey="Eriksson M" first="Mikael" last="Eriksson">Mikael Eriksson</name></author><author><name sortKey="Humpreys, Keith" sort="Humpreys, Keith" uniqKey="Humpreys K" first="Keith" last="Humpreys">Keith Humpreys</name></author><author><name sortKey="Darabi, Hatef" sort="Darabi, Hatef" uniqKey="Darabi H" first="Hatef" last="Darabi">Hatef Darabi</name></author><author><name sortKey="Olson, Janet E" sort="Olson, Janet E" uniqKey="Olson J" first="Janet E" last="Olson">Janet E. Olson</name></author><author><name sortKey="Stevens, Kristen N" sort="Stevens, Kristen N" uniqKey="Stevens K" first="Kristen N" last="Stevens">Kristen N. Stevens</name></author><author><name sortKey="Vachon, Celine M" sort="Vachon, Celine M" uniqKey="Vachon C" first="Celine M" last="Vachon">Celine M. Vachon</name></author><author><name sortKey="Knight, Julia A" sort="Knight, Julia A" uniqKey="Knight J" first="Julia A" last="Knight">Julia A. Knight</name></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name></author><author><name sortKey="Mulligan, Anna Marie" sort="Mulligan, Anna Marie" uniqKey="Mulligan A" first="Anna Marie" last="Mulligan">Anna Marie Mulligan</name></author><author><name sortKey="Ashworth, Alan" sort="Ashworth, Alan" uniqKey="Ashworth A" first="Alan" last="Ashworth">Alan Ashworth</name></author><author><name sortKey="Orr, Nicholas" sort="Orr, Nicholas" uniqKey="Orr N" first="Nicholas" last="Orr">Nicholas Orr</name></author><author><name sortKey="Schoemaker, Minouk" sort="Schoemaker, Minouk" uniqKey="Schoemaker M" first="Minouk" last="Schoemaker">Minouk Schoemaker</name></author><author><name sortKey="Webb, Penny M" sort="Webb, Penny M" uniqKey="Webb P" first="Penny M" last="Webb">Penny M. Webb</name></author><author><name sortKey="Guenel, Pascal" sort="Guenel, Pascal" uniqKey="Guenel P" first="Pascal" last="Guénel">Pascal Guénel</name></author><author><name sortKey="Brauch, Hiltrud" sort="Brauch, Hiltrud" uniqKey="Brauch H" first="Hiltrud" last="Brauch">Hiltrud Brauch</name></author><author><name sortKey="Giles, Graham" sort="Giles, Graham" uniqKey="Giles G" first="Graham" last="Giles">Graham Giles</name></author><author><name sortKey="Garcia Closas, Montserrat" sort="Garcia Closas, Montserrat" uniqKey="Garcia Closas M" first="Montserrat" last="García-Closas">Montserrat García-Closas</name></author><author><name sortKey="Czene, Kamila" sort="Czene, Kamila" uniqKey="Czene K" first="Kamila" last="Czene">Kamila Czene</name></author><author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J" last="Couch">Fergus J. Couch</name></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L" last="Andrulis">Irene L. Andrulis</name></author><author><name sortKey="Swerdlow, Anthony" sort="Swerdlow, Anthony" uniqKey="Swerdlow A" first="Anthony" last="Swerdlow">Anthony Swerdlow</name></author><author><name sortKey="Hunter, David J" sort="Hunter, David J" uniqKey="Hunter D" first="David J" last="Hunter">David J. Hunter</name></author><author><name sortKey="Flesch Janys, Dieter" sort="Flesch Janys, Dieter" uniqKey="Flesch Janys D" first="Dieter" last="Flesch-Janys">Dieter Flesch-Janys</name></author><author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F" last="Easton">Douglas F. Easton</name></author><author><name sortKey="Hall, Per" sort="Hall, Per" uniqKey="Hall P" first="Per" last="Hall">Per Hall</name></author><author><name sortKey="Nevanlinna, Heli" sort="Nevanlinna, Heli" uniqKey="Nevanlinna H" first="Heli" last="Nevanlinna">Heli Nevanlinna</name></author><author><name sortKey="Kraft, Peter" sort="Kraft, Peter" uniqKey="Kraft P" first="Peter" last="Kraft">Peter Kraft</name></author><author><name sortKey="Chang Claude, Jenny" sort="Chang Claude, Jenny" uniqKey="Chang Claude J" first="Jenny" last="Chang-Claude">Jenny Chang-Claude</name></author></analytic><series><title level="j">Endocrine-related cancer</title><idno type="eISSN">1479-6821</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biomarkers, Tumor (genetics)</term><term>Breast Neoplasms (etiology)</term><term>Carcinoma, Lobular (etiology)</term><term>Case-Control Studies</term><term>Female</term><term>Genes, Modifier (genetics)</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Hormone Replacement Therapy (adverse effects)</term><term>Humans</term><term>Meta-Analysis as Topic</term><term>Polymorphism, Single Nucleotide (genetics)</term><term>Prognosis</term><term>Risk Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Biomarkers, Tumor</term></keywords><keywords scheme="MESH" qualifier="adverse effects" xml:lang="en"><term>Hormone Replacement Therapy</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Breast Neoplasms</term><term>Carcinoma, Lobular</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genes, Modifier</term><term>Polymorphism, Single Nucleotide</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Case-Control Studies</term><term>Female</term><term>Genetic Predisposition to Disease</term><term>Genome-Wide Association Study</term><term>Humans</term><term>Meta-Analysis as Topic</term><term>Prognosis</term><term>Risk Factors</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24080446</PMID><DateCreated><Year>2013</Year><Month>11</Month><Day>05</Day></DateCreated><DateCompleted><Year>2014</Year><Month>06</Month><Day>26</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1479-6821</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>6</Issue><PubDate><Year>2013</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Endocrine-related cancer</Title><ISOAbbreviation>Endocr. Relat. Cancer</ISOAbbreviation></Journal><ArticleTitle>Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.</ArticleTitle><Pagination><MedlinePgn>875-87</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1530/ERC-13-0349</ELocationID><Abstract><AbstractText>Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rudolph</LastName><ForeName>Anja</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120 Heidelberg, Germany PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Foundation for Quality and Efficiency in Health Care (IQWIG), Cologne, Germany Human Genetics, Genome Institute of Singapore, Singapore, Singapore Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK INSERM (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France Unité Mixte de Recherche Scientifique (UMRS) 1018, University Paris-Sud, Villejuif, France Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany Institute for Occupational Medicine and Maritime Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany Institute of Pathology, University of Bonn, Bonn, Germany Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria, Australia Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia Division of Cancer Epidemiology and Genetics, N</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hein</LastName><ForeName>Rebecca</ForeName><Initials>R</Initials></Author><Author ValidYN="Y"><LastName>Lindström</LastName><ForeName>Sara</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Beckmann</LastName><ForeName>Lars</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Behrens</LastName><ForeName>Sabine</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jianjun</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Aschard</LastName><ForeName>Hugues</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Bolla</LastName><ForeName>Manjeet 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States</Country></Grant><Grant><GrantID>C5047/A8384</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>C12292/A11174</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>R01 CA128978</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><GrantID>U19 CA148537</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 CA116201</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U01 CA098233</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>1U19 CA148112</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C1281/A12014</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>U19 CA148112</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C1287/A10710</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>U19 CA148065</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA122340</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 CA049449</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>CA50385</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C1287/A10118</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>U01 CA049449</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>10118</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>CA65725</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>C5047/A15007</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>10124</GrantID><Agency>Cancer Research UK</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, 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