AbstractsMedical & Health Science

BRCA1/2 mutation carriers are at a significantly increased risk for breast and ovarian cancer as compared to women in the general population. The cancer risk estimates for mutation carriers show however considerable variation. More accurate, personal risk estimation would be beneficial for counseling and decision making regarding breast cancer screening and preventive surgery. The aim of this thesis was to improve the breast and ovarian cancer risk estimates for BRCA1/2 carriers and their female relatives, by explaining the risk variation and developing subgroup specific risk estimates. Therefore methodology and population characteristics – i.e. mutation status, mutation spectrum, family history, birth cohort – were assessed in families that were referred for genetic testing. The results showed that the reported variation in cancer risk estimates for BRCA1/2 carriers is mainly due to differences in the applied methodology, whereas differences between women have a smaller effect. Non-carriers in BRCA1/2 families appeared to be at a slightly increased risk for breast cancer in their forties as compared to the general population. Differences in the mutation spectrum only partially explained the regional differences among Dutch carriers, and the breast cancer risk did not depend on whether the mutation was paternally or maternally inherited. The breast cancer risk in mutation carriers above age 60 was still significantly increased, and annual screening detected their tumors in a more favorable stage. Application of the above findings will improve risk counselling of BRCA1/2 mutation carriers, and further evaluation of the breast screening protocols in these families is warranted to optimized surveillance. Advisors/Committee Members: Hoogerbrugge, Nicoline (assessment_committee), Moons, K.G.M. (assessment_committee), Sijmons, Rolf (assessment_committee).