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dc.contributor.advisorPaulssen, Ruth
dc.contributor.authorKrum-Hansen, Sanda
dc.date.accessioned2024-03-07T10:32:35Z
dc.date.available2024-03-07T10:32:35Z
dc.date.issued2024-04-04
dc.description.abstractThe incidence and prevalence of breast cancer (BC) are increasing worldwide. The reasons for this trend are partly unknown. BC has several well documented modifiable and non-modifiable risk factors. The only known, natural protective factors are breastfeeding and parity. The current paradigm is that the protective effect of parity is mediated by permanent genomic changes in a woman’s breast tissue during her first pregnancy. Many gene expression studies examining breast carcinogenesis, have used a variety of non-cancerous, but not truly normal samples of breast tissue as controls. We performed a series of studies with a systems epidemiology approach to explore association between breast cancer and parity in a postmenopausal population. The NOWAC study is a prospective national cohort study of 172 000 Norwegian women included between 1991 and 2007. Data is collected from questionnaires and linked national registries. We found that the women in the Norwegian Women and Cancer Study had a decreasing cumulative incidence rate (CIR) of BC of 0.8% per child, rather than only for the first child. This finding was consistent irrespective of other risk factors and is in line with past studies. We performed two gene expression studies using microarray technology in order to explore the biological processes underlying this protective effect. To ensure the best possible source of normal tissue, we collected breast tissue samples of 400 healthy postmenopausal women from the same NOWAC cohort. Gene expression profiles of 311 of these samples showed no genomic changes associated with parity, although we did find genomic changes associated with obesity, smoking and alcohol. Next, we performed a nested case control study of 311 pairs of the same healthy cohort and women with breast cancer in the NOWAC study. We found no impact of parity on global gene expression levels in either cohort. In conclusion we find that parity is a protective factor for BC for each additional child, not only the first full term pregnancy. However, we find no evidence that parity is associated with permanent genomic changes in normal breast tissue or breast cancer tissue.en_US
dc.description.abstractInsidensen og prevelansen av brystkreft (BK) øker globalt. Årsakene til dette er ikke kjent. BK har en rekke veldokumenterte modifiserbare og ikke-modifiserbare risikofaktorer. De eneste kjente beskyttende faktorene er amming og paritet. Den rådende teorien for å forklare dette er at den beskyttende effekten av paritet er mediert av permanente genomiske endringer i en kvinnes brystvev i løpet av hennes første svangerskap. Mange genekspresjonsstudier som undersøker utvikling av brystkreft, har brukt ulike ikke-maligne, men ikke egentlige normale, prøver fra brystvev som kontroller. Vi utførte en serie studier med en systemepidemiologisk tilnærming for å utforske dette nærmere i en postmenopausal populasjon. NOWAC-studien er en prospektiv nasjonal kohortstudie av 172 000 norske kvinner inkludert mellom 1991 og 2007. Data samles fra spørreskjema og koblede nasjonale registre. Vi fant at kvinner i Kviner og Kreft studien hadde reduksjon av kumulative insidens-rate for bryst kreft på 0.8% per barn, ikke kun for det første barnet. Dette funnet var konsistent uavhengig av andre risikofaktorer, og i tråd med tidligere studier. Vi utførte to genekspresjonsstudier med mikromatrise-teknologi for å undersøke de biologiske prosessene bak denne beskyttende effekten. For å benytte den beste kilden til normalt vev, samlet vi brystvevsbiopsier fra 400 friske postmenopausale kvinner fra den samme NOWAC-kohorten. Genekspresjonsprofiler av 311 av disse biopsiene viste ingen genomiske endringer assosiert med paritet, men vi fant genomiske endringer assosiert med overvekt, røyking og alkohol. Deretter utførte vi en nøstet kasus-kontroll-studie av 311 par fra den samme friske kohorten og kvinner med BK i NOWAC-studien. Vi fant ingen innvirkning av paritet på globale genekspresjonsnivå i noen av kohortene. For å konkludere, finner vi at paritet er en beskyttende faktor for BK for hvert barn, ikke bare det første fullgåtte svangerskapet. Derimot finner vi ingen holdepunkter for at paritet er assosiert med permanente genomiske forandringer i normalt brystvev eller i brystkreftvev.  en_US
dc.description.doctoraltypeph.d.en_US
dc.description.popularabstractSummary The incidence and prevalence of breast cancer (BC) are increasing worldwide. The reasons for this trend are partly unknown. BC has several well documented modifiable and non-modifiable risk factors. The only known, natural protective factors are breastfeeding and parity. The current paradigm is that the protective effect of parity is mediated by permanent genomic changes in a woman’s breast tissue during her first pregnancy. Many gene expression studies examining breast carcinogenesis, have used a variety of non-cancerous, but not truly normal samples of breast tissue as controls. We performed a series of studies with a systems epidemiology approach to explore association between breast cancer and parity in a postmenopausal population. The NOWAC study is a prospective national cohort study of 172 000 Norwegian women included between 1991 and 2007. Data is collected from questionnaires and linked national registries. We found that the women in the Norwegian Women and Cancer Study had a decreasing cumulative incidence rate (CIR) of BC of 0.8% per child, rather than only for the first child. This finding was consistent irrespective of other risk factors and is in line with past studies. We performed two gene expression studies using microarray technology in order to explore the biological processes underlying this protective effect. To ensure the best possible source of normal tissue, we collected breast tissue samples of 400 healthy postmenopausal women from the same NOWAC cohort. Gene expression profiles of 311 of these samples showed no genomic changes associated with parity, although we did find genomic changes associated with obesity, smoking and alcohol. Next, we performed a nested case control study of 311 pairs of the same healthy cohort and women with breast cancer in the NOWAC study. We found no impact of parity on global gene expression levels in either cohort. In conclusion we find that parity is a protective factor for BC for each additional child, not only the first full term pregnancy. However, we find no evidence that parity is associated with permanent genomic changes in normal breast tissue or breast cancer tissue.en_US
dc.description.sponsorshipUiTen_US
dc.identifier.urihttps://hdl.handle.net/10037/33131
dc.language.isoengen_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.relation.haspart<p>Paper I: Krum-Hansen, S., Wiik, A.B., Olsen, K.S., Lukic, M., Paulssen, R.H. & Lund, E. Parity and cumulative incidence rates of breast cancer in the Norwegian Woman and Cancer Study (NOWAC). (Submitted manuscript). <p>Paper II: Krum-Hansen, S. & Olsen, K.S. (2020). Chapter 4. Practical and Ethical Issues in Establishing a Collection of Normal Breast Tissue Biopsies— Part of the NOWAC Post-Genome Cohort. In: Lund, E. (Ed.), <i>Advancing Systems Epidemiology in Cancer. Exploring Trajectories of Gene Expression</i>. (pp 63-76). Scandinavian University Press. Also available in Munin at <a href=https://hdl.handle.net/10037/27081>https://hdl.handle.net/10037/27081</a>. <p>Paper III: Krum-Hansen, S., Olsen, K.S., Anderssen, E., Frantzen, J.O., Lund, E. & Paulssen, R.H. (2023). Associations of breast cancer related exposures and gene expression profiles in normal breast tissue – The Norwegian Women and Cancer (NOWAC) normal breast tissue study. <i>Cancer Reports, 6</i>(4), e1777. Also available in Munin at <a href=https://hdl.handle.net/10037/28508>https://hdl.handle.net/10037/28508</a>. <p>Paper IV: Lund, E., Krum-Hansen, S., Olsen, K.S., Shvetsov, N., Snapkow, I., Gavriluk, O., Busund, L.T.R., Frantzen, J.O., Holden, M. & Holden, L. No impact of parity on global gene expression levels in breast cancer tissue and normal breast tissue – a nested case-control study in the NOWA Postgenomic biobank. (Submitted manuscript).en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)en_US
dc.subjectParityen_US
dc.subjectBreast Canceren_US
dc.subjectGene expressionen_US
dc.titleA Systems Epidemiology Approach to Breast Cancer and Parity. The Norwegian Women and Cancer (NOWAC) Studyen_US
dc.typeDoctoral thesisen_US
dc.typeDoktorgradsavhandlingen_US


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