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Genome-wide association studies identify four ER negative–specific breast cancer risk loci

Authors: Montserrat Garcia-Closas; Fergus J. Couch; Sara Lindström; Kyriaki Michailidou; Marjanka K. Schmidt; Mark N. Brook; Nick Orr; +208 Authors

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

Abstract

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Countries
United Kingdom, Netherlands, Ireland, Italy
Subjects by Vocabulary

Microsoft Academic Graph classification: Oncology Estrogen receptor Genome-wide association study Bioinformatics Genotype medicine.medical_specialty Single-nucleotide polymorphism Biology Breast cancer Internal medicine medicine Genetic predisposition Case-control study Cancer medicine.disease

Keywords

genetic association, body-mass index, cancer risk, susceptibility, chromosome 1q, single nucleotide polymorphism, Risk Factors, estrogen, Cooperative Behavior, comparative study, Oligonucleotide Array Sequence Analysis, chromosome 16q, priority journal, Receptors, Estrogen, Female, cancer invasion, signal transduction, breast cancer; cancer invasion; cancer risk; chromosome 1; chromosome 16q; chromosome 1q; chromosome 2p; comparative study; follow up; gene locus; genetic association; genetic susceptibility; human; nucleotide sequence; priority journal; signal transduction; single nucleotide polymorphism, gene locus, Genotype, Breast Neoplasms, Polymorphism, Single Nucleotide, Article, breast cancer, SDG 3 - Good Health and Well-being, Meta-Analysis as Topic, expression, Genetics, follow up, Humans, Genetic Predisposition to Disease, human, gene, chromosome 1, nucleotide sequence, chromosome 2p, Genetic Loci, common variant, Case-Control Studies, genetic susceptibility, Genome-Wide Association Study

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    visibility views 15
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  • citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    393
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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visibility
download
citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
OpenAIRE UsageCountsDownloads provided by UsageCounts
393
Top 1%
Top 1%
Top 0.1%
15
127
Funded byView all
NIH| Breast &prostate cancer &hormone-related gene variants
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1U01CA098216-01
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Characterizing Genetic Susceptibility to Breast and Prostate Cancer: The BPC3.
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5U01CA098710-06
  • Funding stream: NATIONAL CANCER INSTITUTE
iis
,
WT
Project
  • Funder: Wellcome Trust (WT)
,
EC| COGS
Project
COGS
Collaborative Oncological Gene-environment Study
  • Funder: European Commission (EC)
  • Project Code: 223175
  • Funding stream: FP7 | SP1 | HEALTH
Validated by funder | sysimport:crosswalk:repository
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