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Interval breast cancer is associated with interferon immune response

Ugalde-Morales, Emilio (author)
Karolinska Institutet,Karolinska Institute
Grassmann, Felix (author)
Karolinska Institutet,Karolinska Institute,Health and Medical University
Humphreys, Keith (author)
Karolinska Institutet,Karolinska Institute
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Li, Jingmei (author)
Karolinska Institute,A*Star, Genome Institute of Singapore (GIS),National University of Singapore
Eriksson, Mikael (author)
Karolinska Institutet,Karolinska Institute
Tobin, Nicholas P. (author)
Karolinska Institutet,Karolinska Institute
Lindström, Linda S. (author)
Karolinska Institutet,Karolinska Institute
Vallon-Christersson, Johan (author)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Borg, Åke (author)
Lund University,Lunds universitet,Create Health,Annan verksamhet, LTH,Lunds Tekniska Högskola,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Familjär bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Other operations, LTH,Faculty of Engineering, LTH,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Familial Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Hall, Per (author)
Karolinska Institutet,Karolinska Institute
Czene, Kamila (author)
Karolinska Institutet,Karolinska Institute
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 (creator_code:org_t)
Elsevier BV, 2022
2022
English 12 s.
In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 162, s. 194-205
Related links:
http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Background: The aggressive nature of breast cancers detected between planned mammographic screens, so-called interval cancers, remains elusive. Here, we aim to characterise underlying molecular features of interval cancer. Methods: From 672 patients with invasive breast cancer, we analysed gene expression differences between 90 ‘true’ interval cancer cases (i.e. women with low-dense breasts defined as per cent mammographic density <25%) and 310 screen-detected tumours while accounting for PAM50 subtypes and thus overall tumour aggressiveness. We computed an interval cancer gene expression profile (IC-Gx) in a total of 2270 breast tumours (regardless of interval cancer status) and tested for association with expression-based immune subtypes in breast cancer. In addition, we investigated the contribution of inherited and somatic genetic variants in distinct features of interval cancer. Results: We identified 8331 genes nominally associated with interval cancer (P-value < 0.05, fold-change > 1.5). Gene set enrichment analysis showed immune-related pathways as key processes altered in interval cancer. Our IC-Gx, based on 47 genes with the strongest associations (false discovery rate < 0.05), was found to be associated mainly with immune subtypes involving interferon response. We isolated an interaction network of interval cancer and interferon genes for which a significant load of somatic and germline variants in class I interferon genes was observed. Conclusion: We identified novel molecular features of interval breast cancer highlighting interferon pathways as a potential target for prevention or treatment.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Interferon immune response
Interval breast cancer
Mammographic density
PAM50 subtypes

Publication and Content Type

art (subject category)
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