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 4,000 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 recent transcriptome-wide association studies. An additional consortial project is being completed by my post-doc, Ann Von Holle, who is looking at the role of BMI in relation to risk of breast cancer as women transition through the peri-menopausal years. 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 other work related to the methylome we will be working with our new NIH Scholars Connect Program scholar, Sahana Ramamurthy to assess a possible relationship between serum iron markers and methylation-based markers of accelerated biologic aging. 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. We are currently looking at modifiable risk factors to assess their time-dependent association with risk of Type 2 Diabetes. 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 a paper now under revision. We are also evaluating predictive models for iron status in a paper soon to be submitted.