Evidence map›Paper›PMID 23423446›Full record

SynthesisBreast cancer research and treatment2013

A genome-wide association study to identify genetic susceptibility loci that modify ductal and lobular postmenopausal breast cancer risk associated with menopausal hormone therapy use: a two-stage design with replication.

Rebecca Hein, Dieter Flesch-Janys, Norbert Dahmen, Lars Beckmann, Sara Lindström, Nils Schoof, Kamila Czene, Kirstin Mittelstraß, Thomas Illig, Petra Seibold and 28 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Breast cancer research and treatment, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020
    Pooled it
  2. Potential Role of Zinc Finger 365Iranian journal of medical sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 17 institutions in 8 countries.

Rebecca Hein *Unit of Genetic Epidemiology, Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
Dieter Flesch-Janys *Department of Cancer Epidemiology, Clinical Cancer Registry, University Cancer Center and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
Norbert DahmenCongenics AG, Hamburg, Germany.
Lars BeckmannUnit of Genetic Epidemiology, Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany; Foundation for Quality and Efficiency in Health Care (IQWIG), Cologne, Germany.
Sara LindströmProgram in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard, School Of Public Health, Boston, MA 02138, USA; Department of Biostatistics, Harvard School Of Public Health, Boston, MA 02138, USA.
Nils SchoofDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kirstin MittelstraßResearch Unit of Molecular Epidemiology, Helmholtz Center Munich, Munich, Germany.
Thomas IlligResearch Unit of Molecular Epidemiology, Helmholtz Center Munich, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Petra SeiboldUnit of Genetic Epidemiology, Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Sabine BehrensUnit of Genetic Epidemiology, Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Keith HumphreysDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jingmei LiHuman,Genetics, Genome Institute of Singapore, 60 Biopolis St, Singapore 138672, Singapore.
Jianjun LiuHuman,Genetics, Genome Institute of Singapore, 60 Biopolis St, Singapore 138672, Singapore.
Janet E OlsonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Xianshu WangDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Susan E HankinsonDepartment of Epidemiology, Harvard, School Of Public Health, Boston, MA 02138, USA.
Thérèse TruongInserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
Florence MenegauxInserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
Isabel Dos Santos SilvaDepartment of Non-Communicable, Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Nichola JohnsonBreakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
GENICA Network
Shou-Tung ChenDepartment of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
Jyh-Cherng YuDepartment of Surgery, Tri-Service General Hospital, Taipei, Taiwan.
Argyrios ZiogasDepartment of Epidemiology, School of Medicine, University of California, Irvine, CA, USA.
Vesa KatajaSchool of Medicine, Institute of Clinical Medicine, Oncology, Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
Veli-Matti KosmaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
Arto MannermaaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
Hoda Anton-CulverDepartment of Epidemiology, University of California Irvine, Irvine, CA, USA.
Chen-Yang ShenInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Taiwan Biobank, Taipei, Taiwan.
Hiltrud BrauchDr. Margarete Fischer-Bosch-Institute, of Clinical Pharmacology, Stuttgart, University of Tübingen, Tübingen, Germany.
Julian PetoDepartment of Non-Communicable, Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Pascal GuénelInserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
Peter KraftProgram in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard School Of Public Health, Boston, MA 02138, USA; Department of Biostatistics, Harvard School Of Public Health, Boston, MA 02138, USA.
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Departments of Public Health and Primary Care and Oncology, University of Cambridge, Cambridge, UK.
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jenny Chang-ClaudeUnit of Genetic Epidemiology, Division of Cancer Epidemiology (C020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
German Cancer Research Center · DEUniversity of Eastern Finland · FIHarvard University · USKarolinska Institutet · SEMassachusetts Department of Public Health · USUniversity of London · GBMayo Clinic in Arizona · USTri-Service General Hospital · TWUniversität Hamburg · DEUniversity of Cambridge · GBGenome Institute of Singapore · SGHelmholtz Zentrum München · DEInserm · FRInstitute of Biomedical Sciences, Academia Sinica · TWInstitute of Cancer Research · GBUniversité Paris-Sud · FRUniversity of California, Irvine · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Risk Factors for Breast Cancer in Younger NursesR01CA050385 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 1989 to 2019
$32.3M
Premonopausal Hormone Levels and Risk of Breast CancerR01CA067262 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HANKINSON, SUSAN E · 2002 to 2011
$11.9M
BIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HANKINSON, SUSAN E · 1989 to 2008
$11.3M
Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3U01CA098233 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HUNTER, DAVID JOHN · 2003 to 2010
$10.8M
BIOCHEMICAL MARKERS IN THE NURSES HEALTH STUDY COHORTU01CA049449 · NCI · UNIVERSITY OF MASSACHUSETTS AMHERST · PI HANKINSON, SUSAN E · 1995 to 2013
$5.4M
A genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8M
COHORT STUDY OF GENETIC SUSCEPTIBILITY TO BREAST CANCERR01CA065725 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HUNTER, DAVID JOHN · 1996 to 2010
$4.5M
HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIESR01CA058860 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANTON-CULVER, HODA A · 1994 to 2008
$3.1M
Genetic epidemiology of cell division regulation in breast cancerR01CA122340 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2007 to 2011
$3.0M
HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIESU01CA058860 · NCI · UNIVERSITY OF CALIFORNIA IRVINE · PI ANTON-CULVER, HODA A. · 1997 to 2002
$2.5M
Cancer Research UK 10118Cancer Research UK 11022NCI NIH HHS 5U01CA098233NCI NIH HHS CA116201NCI NIH HHS CA122340NCI NIH HHS CA128978NCI NIH HHS CA49449NCI NIH HHS CA50385NCI NIH HHS CA58860NCI NIH HHS CA65725NCI NIH HHS CA67262NCI NIH HHS CA87969NCI NIH HHS CA92044NCI NIH HHS K07 CA092044NCI NIH HHS P01 CA087969NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA050385NCI NIH HHS R01 CA058860NCI NIH HHS R01 CA065725NCI NIH HHS R01 CA067262NCI NIH HHS R01 CA122340NCI NIH HHS R01 CA128978NCI NIH HHS R01 CA58427NCI NIH HHS U01 CA049449NCI NIH HHS U01 CA058860NCI NIH HHS U01 CA067262NCI NIH HHS U01 CA098233
6 · The paper itself

Abstract

Menopausal hormone therapy (MHT) is associated with an elevated risk of breast cancer in postmenopausal women. To identify genetic loci that modify breast cancer risk related to MHT use in postmenopausal women, we conducted a two-stage genome-wide association study (GWAS) with replication. In stage I, we performed a case-only GWAS in 731 invasive breast cancer cases from the German case-control study Mammary Carcinoma Risk Factor Investigation (MARIE). The 1,200 single nucleotide polymorphisms (SNPs) showing the lowest P values for interaction with current MHT use (within 6 months prior to breast cancer diagnosis), were carried forward to stage II, involving pooled case-control analyses including additional MARIE subjects (1,375 cases, 1,974 controls) as well as 795 cases and 764 controls of a Swedish case-control study. A joint P value was calculated for a combined analysis of stages I and II. Replication of the most significant interaction of the combined stage I and II was performed using 5,795 cases and 5,390 controls from nine studies of the Breast Cancer Association Consortium (BCAC). The combined stage I and II yielded five SNPs on chromosomes 2, 7, and 18 with joint P values <6 × 10(-6) for effect modification of current MHT use. The most significant interaction was observed for rs6707272 (P = 3 × 10(-7)) on chromosome 2 but was not replicated in the BCAC studies (P = 0.21). The potentially modifying SNPs are in strong linkage disequilibrium with SNPs in TRIP12 and DNER on chromosome 2 and SETBP1 on chromosome 18, previously linked to carcinogenesis. However, none of the interaction effects reached genome-wide significance. The inability to replicate the top SNP × MHT interaction may be due to limited power of the replication phase. Our study, however, suggests that there are unlikely to be SNPs that interact strongly enough with MHT use to be clinically significant in European women.

Indexed as

Breast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularCase-Control StudiesChromosomes, HumanEstrogen Replacement TherapyEstrogensFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLinkage DisequilibriumPolymorphism, Single NucleotidePostmenopauseProgestinsEstrogensProgestins

Identifiers

PMID23423446
PMCPMC3781176
OpenAlexW2032962465

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.