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Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).ORCID iD: 0000-0001-8603-8293
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).ORCID iD: 0000-0002-7674-2014
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2018 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 20, article id 14Article in journal (Refereed) Published
Abstract [en]

Background: Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density. Methods: Plasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI). Results: Plasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p < 0.05). Plasma levels of seven proteins were positively associated and 13 proteins negatively associated with AD. For eleven of these proteins evidence for gene expression in breast tissue existed. Among these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated with AD. Conclusions: Screening proteins in plasma indicates associations between breast density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD , 2018. Vol. 20, article id 14
Keywords [en]
Mammographic breast density, Plasma, Protein profiling, Suspension bead array, Affinity proteomics, KARMA cohort
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-223790DOI: 10.1186/s13058-018-0940-zISI: 000425114200001PubMedID: 29444691Scopus ID: 2-s2.0-85042063089OAI: oai:DiVA.org:kth-223790DiVA, id: diva2:1188295
Funder
Swedish Research CouncilThe Kamprad Family FoundationKnut and Alice Wallenberg FoundationSwedish Cancer SocietyScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180307

Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-07Bibliographically approved

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Byström, SannaHong, Mun-GwanFredolini, ClaudiaSchwenk, Jochen M.

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Byström, SannaHong, Mun-GwanFredolini, ClaudiaSchwenk, Jochen M.
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