The Sister Study: Genetic and Environmental Risk Factors for Breast Cancer

The Sister Study is prospectively examining environmental and familial risk factors for breast cancer and other diseases in a cohort of 50,884 sisters of women who have had breast cancer. Such sisters have about twice the risk of developing breast cancer as other women. The frequency of any relevant genes and shared risk factors will also be higher. Studying sisters enhances our ability to understand the interplay of genes and environment in breast cancer risk and to identify potentially preventable risk factors. We assess exposures before the onset of disease, thus avoiding biases common to retrospective studies. The assembled cohort has created a framework from which to test new hypotheses as they emerge.

Cancer-free sisters aged 35-74 were recruited nationally. Enrollment was completed July 2009 with 50,884 women fully enrolled. Participants have enrolled from all 50 states and Puerto Rico. The cohort is now being followed actively. Cohort members are occasionally invited to participate in add-on studies, which sometimes include asking participants to invite their family members to provide information.

Data on potential risk factors and current health status were collected with telephone interviews and self-completed questionnaires. Blood, urine, and environmental samples were collected and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. The cohort is being followed prospectively for 10 or more years. Annual questionnaires update medical history and changes in exposures. About 300 new cases of breast cancer are expected to occur in the cohort each year. Analyses are ongoing and assess the independent and combined effects of environmental exposures and genetic polymorphisms that affect estrogen metabolism, DNA repair, and response to specific environmental exposures. Future analyses will focus on known and potential risk factors (e.g. smoking, occupational exposures, alcohol, diet, obesity) and include measurement of phthalates, phytoestrogens, insulin, growth factors, micro-nutrients, and genes. Women who develop breast cancer during the study are followed to assess the role of environment and genes in healthy survival following diagnosis and treatment. The cohort will also be used to explore risk for other diseases (e.g. heart disease, osteoporosis, other hormonal cancers, and autoimmune diseases) that are important for women.