Epithelial ovarian cancer. Population-based cohort studies. The NOWAC Study and Postgenome biobank

Abstract

Important gaps in population-based epidemiological research on ovarian cancer include understanding how risk factors relate to cancer subtypes and anatomical sites, identifying safe and effective preventive measures, and getting a more detailed picture of the continuum of events during ovarian carcinogenesis. This thesis used prospective exposure information from the Norwegian Women and Cancer (NOWAC) Study and blood samples from the NOWAC Postgenome biobank to explore topics within these gaps. On the topic of risk factors, subtypes and anatomical sites, previous studies have shown that serous carcinomas of the ovary and fallopian tube cancers have similar risk factors. This thesis compared risk factors between the ovary/fallopian tube and uterine corpus. One risk factor association separated serous carcinomas of these sites, while no differences in risk factor associations were found for endometrioid and clear cell carcinomas. Possible alternative explanations of this result include few observations in the analysis of endometrioid and clear cell carcinomas, and histological misclassification of high-grade endometrioid carcinomas. Among preventive measures, combined oral contraceptives reduce the risk of both ovarian and uterine carcinoma. Current trends in female contraception include an increase in use of progestin-only long-acting reversible contraceptives, such as the levonorgestrel-releasing intrauterine system (LNG-IUS). In the NOWAC cohort, ever use of LNG-IUS reduced the risk of ovarian carcinoma by 53% (95% CI: 22% – 68%) and the risk of uterine carcinoma by 78% (95% CI: 60% – 87%) compared to never use. These results extend current knowledge to include postmenopausal women in a sample of the general population. The association with breast cancer was also investigated and discussed. To investigate the continuum of events during ovarian carcinogenesis, this thesis explores gene expression in peripheral blood in the years preceding ovarian cancer diagnosis. The presented study did not find strong associations. This could be because there is little association between ovarian cancer and prediagnostic gene expression in blood, but could also be due to a small sample size, or the analytic approach that was used.

Kreft i eggstokkene er forholdsvis sjelden kreftform, som har høy dødelighet. Denne doktoravhandlingen bygger på spørreskjema fra 172000 kvinner i Kvinner og kreft-studien, og på blodprøver fra 50000 av deltakerne. Blodprøvene utgjør en unik biobank med bevart genuttrykk fra de hvite blodlegemene. Fra før vet man at kvinner som har brukt p-piller har lavere risiko for eggstokkreft. I dag har mange kvinner, også de yngre, begynt å bruke hormonspiral. Det er lite kunnskap om hvorvidt kvinner som bruker hormonspiral har lavere risiko for eggstokkreft slik som p-pillebrukerne. Blant de noe eldre deltakerne i Kvinner og kreft hadde kvinner som noen gang har brukt hormonspiral en halvert risiko for eggstokkreft. Fordi det var få tilfeller, har anslaget en usikkerhet som tilsvarer mellom 10% og 70% lavere risiko. Blodprøvene i biobanken gir mulighet til å undersøke endringer i genuttrykk i immunceller opptil sju år før diagnosen ble stilt, i håp om å forstå mer om sykdomsutviklingen. Vi gjorde en utforskende analyse av blodprøver fra kvinner som hadde fått eggstokkreft, men fant ikke entydige endringer i genuttrykket.