The Two Sister Study

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

As discussed in our published overview of the study, we enrolled 50,884 US and Puerto Rican women who were between the ages of 35 and 74 and had a sister with breast cancer but did not have breast cancer themselves when they joined the study between 2003 and 2009. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mailed questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies. More than 3,000 Sister Study participants have reported a diagnosis of invasive or in situ breast cancer. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires on health outcomes, environmental and lifestyle exposures, and special topics are completed every 2-3 years. We retrieve medical records and tumor tissue for those who develop cancer or other conditions of interest. Breast cancer and ovarian cancer cases through 2014 and a random sample of the cohort have been genotyped as part of the multi-study Oncoarray project. Through this project, Sister Study and Two Sister Study data have been included in several collaborative analyses, including two recent transcriptome-wide association studies. Two consortial projects that were headed up by my former postdoc (O'Brien, et al.), now a Staff Scientist in the Epidemiology Branch, considered the use of perineal powder in relation to risk of uterine cancer and cervical cancer. We also previously generated data on 450,000 CpGs for the non-Hispanic white women in the genotyping sample, with plans to evaluate methylation patterns in relation to risk factors of interest. In work with a postdoc in the Epidemiology Branch (Kresovich, et al., in press at Molecular Oncology) we developed a methylation-based risk score for breast cancer. This score performed very well in test data and in an independent case-control data set from a substudy of the European EPIC study. It provides a novel risk factor that is evidently as strong as predictor for breast cancer as any known risk factor (excepting age and sex) and is independent of the known risk factors. In work now published (Diaz, et al.), we used the Two Sister Study data to assess very early life experiences in relation to risk of young-onset (under age 50) breast cancer and found evidence that women born to a preeclamptic pregnancy were at increased risk, particularly when adjustment is made in the logistic model for whether they had later gestated a preeclamptic pregnancy themselves. We are now following up this work with analyses based on the prospective Sister Study. In other work with Von Holle we found that if an older sister was diagnosed with breast cancer the risk for the studied sister increased when her age was close to the age of the affected sister, even if that onset was later in life. Taken together, these studies suggest very early influences on a life trajectory, perhaps acting synergistically with genetic factors. In other work with Diaz Santana we are using the Sister Study data to study incidence of Type 2 Diabetes. We showed that women with a history of gestational diabetes remain at increased risk of diabetes even late in life. Iron is a growth factor that is essential to life and also promotes lipid peroxidation and the formation of reactive oxygen species (ROS). We are continuing to analyse predictors of iron levels and are comparing biomarkers based on blood with levels measured in toenail clippings, in work soon to be submitted. We are also evaluating predictive models for iron status.