Evidence map›Paper›PMID 28840378›Full record

ArticleBreast cancer research and treatment2017

Panel sequencing of 264 candidate susceptibility genes and segregation analysis in a cohort of non-BRCA1, non-BRCA2 breast cancer families.

Jun Li, Hongyan Li, Igor Makunin, kConFab Investigators, Bryony A Thompson, Kayoko Tao, Erin L Young, Jacqueline Lopez, Nicola J Camp, Sean V Tavtigian and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. GermlineFrontiers in genetics · 2020
    Article
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

15 authors at 6 institutions in 3 countries.

Jun LiQIMR Berghofer, Brisbane, QLD, 4006, Australia.
Hongyan LiHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Igor MakuninQIMR Berghofer, Brisbane, QLD, 4006, Australia.
kConFab Investigators
Bryony A ThompsonHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Kayoko TaoHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Erin L YoungHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Jacqueline LopezHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Nicola J CampHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Sean V TavtigianHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Esther M JohnDepartment of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, 94538, USA.
Irene L AndrulisLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.
Kum Kum KhannaQIMR Berghofer, Brisbane, QLD, 4006, Australia.
David GoldgarHuntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, 84132, USA.
Georgia Chenevix-TrenchQIMR Berghofer, Brisbane, QLD, 4006, Australia. georgiaT@qimr.edu.au.ORCID http://orcid.org/0000-0002-1878-2587
QIMR Berghofer Medical Research Institute · AUUniversity of Utah · USCancer Prevention Institute of California · USThe University of Melbourne · AUThe University of Queensland · AUUniversity of Toronto · CA

Funding

Breast Cancer Family Registry CohortUM1CA164920 · NCI · CANCER PREVENTION INSTIT OF CALIFORNIA · PI ANDRULIS, IRENE, BUYS, SAUNDRA S · 2012 to 2017
$12.7M
Shared Genomic Segment Analysis and Tumor Subtyping in High-Risk BrCa PedigreesR01CA163353 · NCI · UNIVERSITY OF UTAH · PI CAMP, NICOLA J. · 2012 to 2016
$2.9M
A comprehensive approach to breast cancer susceptibility across the risk spectrumR01CA155767 · NCI · UNIVERSITY OF UTAH · PI GOLDGAR, DAVID E., SOUTHEY, MELISSA · 2011 to 2015
$2.2M
NCI NIH HHS R01 CA155767NCI NIH HHS R01 CA163353NCI NIH HHS UM1 CA164920
6 · The paper itself

Abstract

purposeThe main aim of this study was to screen epigenetic modifier genes and known breast cancer driver genes for germline mutations in non-BRCA1/2 (BRCAx) breast cancer families in order to identify novel susceptibility genes of moderate-high penetrance.

methodsWe screened 264 candidate susceptibility genes in 656 index cases from non-BRCA1/2 families. Potentially pathogenic candidate mutations were then genotyped in all available family members for the assessment of co-segregation of the variant with disease in the family in order to estimate the breast cancer risks associated with these mutations. For 11 of the candidate susceptibility genes, we screened an additional 800 non-BRCA1/2 breast cancer cases and 787 controls.

resultsOnly two genes, CHD8 and USH2A showed any evidence of an increased risk of breast cancer (RR = 2.40 (95% CI 1.0-7.32) and 2.48 (95% CI 1.11-6.67), respectively).

conclusionsWe found no convincing evidence that epigenetic modifier and known breast cancer driver genes carry germline mutations that increase breast cancer risk. USH2A is no longer regarded as a breast cancer driver gene and seems an implausible candidate given its association with Usher syndrome. However, somatic mutations in CHD8 have been recently reported, making it an even more promising candidate, but further analysis of CHD8 in very large cohorts of families or case-control studies would be required to determine if it is a moderate-risk breast cancer susceptibility gene.

Indexed as

Genetic Predisposition to DiseaseAdultBRCA1 ProteinBRCA2 ProteinBreast NeoplasmsDNA-Binding ProteinsEpigenesis, GeneticExtracellular Matrix ProteinsFemaleGene Expression Regulation, NeoplasticGerm-Line MutationHumansMiddle AgedPedigreeRiskTranscription FactorsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanCHD8 protein, humanDNA-Binding ProteinsExtracellular Matrix ProteinsTranscription FactorsUSH2A protein, humanBreast cancerChromatin modification genesMutationSegregationSusceptibility gene

Identifiers

PMID28840378
PMCPMC6238949
OpenAlexW2746993714

What OpenQuestion holds

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Registered trials

None linked

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.