Aspects of breast cancer risk: subtypes of breast cancer, relation to angiogenic factors and gene-environment interactions

-

This proposal describes 3 specific studies, each with several specific aims. The first is a case-control study nested within a cohort of 30,000 pregnant women who have been followed for 10 years after pregnancy. Blood was collected three times during pre gnancy, and we will compare pro- and anti-angiogenic factors in pregnancy and subsequent risk of breast cancer in 152 women who were diagnosed during follow-up and 300 age-matched controls. The second study is a cohort of 20,000 women who participated i n a breast cancer screening more than 45 years ago. Only a fraction of these women are alive, and more than 1500 have developed breast cancer. We want to use tissue micro array technology and determine three subtypes of breast cancer in these women. We wi ll assess the association of conventional (especially reproductive factors) risk factors with each subtype to find out if all subtypes of breast cancer are similarly associated with the established risk factors for this disease. In this study, we will als o investigate the prognosis of each subtype of breast cancer. In the third study, we have followed approximately 35,000 women for 9 years, and 460 have developed breast cancer. These women have participated in an international consortium on genetic facto rs and breast cancer risk, and the association of 90 genetic variants with breast cancer risk have been determined. We want to use these genetic variants and study their interaction with conventional risk factors (reproductive factors, height, weight etc) in relation to breast cancer risk. We also want to explore the possible gene-environment interactions in relation to breast cancer subtypes determined with tissue micro array. For this part of the proposal, we will attempt to analyse the data in collabo ration with other cohort studies, preferably the Nurses' Health Study, to increase the statistical power of the study.