Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density
Abstract 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 th...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-018-0940-z |
| _version_ | 1819175186387173376 |
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| author | Sanna Byström Martin Eklund Mun-Gwan Hong Claudia Fredolini Mikael Eriksson Kamila Czene Per Hall Jochen M. Schwenk Marike Gabrielson |
| author_facet | Sanna Byström Martin Eklund Mun-Gwan Hong Claudia Fredolini Mikael Eriksson Kamila Czene Per Hall Jochen M. Schwenk Marike Gabrielson |
| author_sort | Sanna Byström |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T20:50:52Z |
| format | Article |
| id | doaj.art-ecdbdae7fe1140e9a9b11d2482906ced |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-22T20:50:52Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-ecdbdae7fe1140e9a9b11d2482906ced2022-12-21T18:13:05ZengBMCBreast Cancer Research1465-542X2018-02-0120111310.1186/s13058-018-0940-zAffinity proteomic profiling of plasma for proteins associated to area-based mammographic breast densitySanna Byström0Martin Eklund1Mun-Gwan Hong2Claudia Fredolini3Mikael Eriksson4Kamila Czene5Per Hall6Jochen M. Schwenk7Marike Gabrielson8Science for Life Laboratory, School of Biotechnology, KTH – Royal Institute of TechnologyDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetScience for Life Laboratory, School of Biotechnology, KTH – Royal Institute of TechnologyScience for Life Laboratory, School of Biotechnology, KTH – Royal Institute of TechnologyDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetScience for Life Laboratory, School of Biotechnology, KTH – Royal Institute of TechnologyDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetAbstract 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.http://link.springer.com/article/10.1186/s13058-018-0940-zMammographic breast densityPlasmaProtein profilingSuspension bead arrayAffinity proteomicsKARMA cohort |
| spellingShingle | Sanna Byström Martin Eklund Mun-Gwan Hong Claudia Fredolini Mikael Eriksson Kamila Czene Per Hall Jochen M. Schwenk Marike Gabrielson Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density Breast Cancer Research Mammographic breast density Plasma Protein profiling Suspension bead array Affinity proteomics KARMA cohort |
| title | Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density |
| title_full | Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density |
| title_fullStr | Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density |
| title_full_unstemmed | Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density |
| title_short | Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density |
| title_sort | affinity proteomic profiling of plasma for proteins associated to area based mammographic breast density |
| topic | Mammographic breast density Plasma Protein profiling Suspension bead array Affinity proteomics KARMA cohort |
| url | http://link.springer.com/article/10.1186/s13058-018-0940-z |
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