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dc.contributor.authorLund, Eiliv
dc.contributor.authorNakamura, Aurelie
dc.contributor.authorSnapkov, Igor
dc.contributor.authorThalabard, Jean-Christophe
dc.contributor.authorOlsen, Karina Standahl
dc.contributor.authorHolden, Lars
dc.contributor.authorHolden, Marit
dc.date.accessioned2019-03-07T11:57:45Z
dc.date.available2019-03-07T11:57:45Z
dc.date.issued2018-04-30
dc.description.abstract<p><i>Background</i>: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological changes during pregnancies. In this work, we studied the pregnancy-associated differences in peripheral blood gene expression profiles between healthy women and women diagnosed with BC in a prospective design.</p> <p><i>Methods</i>: Using an integrated system epidemiology approach, we modeled BC incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort (165,000 women) and then tested the resulting mathematical model using gene expression profiles in blood in a nested case–control study (460 invasive case–control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets.</p> <p><i>Results</i>: A linear trend fitted the dataset precisely showing an 8% decrease in risk of BC for each FTP, independent of stratification on other risk factors and lasting for decades after a woman’s last FTP. Women with six children demonstrated 48% reduction in the incidence of BC compared to nulliparous. When we looked at gene expression, we found that 756 genes showed linear trends in cancer-free controls (false discovery rate [FDR] 5%), but this was not the case for any of the genes in BC cases. Gene set enrichment analysis of immunologic gene sets (C7 collection in Molecular Signatures Database) revealed 215 significantly enriched human gene sets (FDR 5%).</p> <p><i>Conclusion</i>: We found marked differences in gene expression and enrichment profiles of immunologic gene sets between BC cases and healthy controls, suggesting an important protective effect of the immune system on BC risk.en_US
dc.descriptionSource at <a href=https://doi.org/10.2147/CLEP.S163208> https://doi.org/10.2147/CLEP.S163208</a>.en_US
dc.identifier.citationLund, E., Nakamura, A., Snapkov, I.S., Thalabard, J.-C., Olsen, K.S., Holden, L. & Holden, M. (2018). Each pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patients. <i>Clinical Epidemiology, 10</i>, 931-940. https://doi.org/10.2147/CLEP.S163208en_US
dc.identifier.cristinIDFRIDAID 1606914
dc.identifier.doi10.2147/CLEP.S163208
dc.identifier.issn1179-1349
dc.identifier.urihttps://hdl.handle.net/10037/14890
dc.language.isoengen_US
dc.publisherDove Medical Pressen_US
dc.relation.journalClinical Epidemiology
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7-IDEAS-ERC/232997/EU/TRANSCRIPTOMICS IN CANCER EPIDEMIOLOGY/TICE/en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectbreast canceren_US
dc.subjectNorwegian Women and Cancer Studyen_US
dc.subjectgene expressionen_US
dc.subjectparityen_US
dc.subjectsemi-allograften_US
dc.subjecthormonesen_US
dc.subjectpregnancyen_US
dc.titleEach pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patientsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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