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Current Research Projects
Title: The Sister Study: A Study of the Environmental and Genetic Risk Factors For Breast Cancer
Summary:The NIEHS Sister Study is prospectively examining environmental and familial risk factors for breast cancer and other diseases in a cohort of 50,000 sisters of women who have had breast cancer. By focusing on a genetically susceptible group, more precise estimates of the contribution of environmental and other non-genetic factors to disease risk may be possible.
The cohort will be followed actively for the development of breast cancer and other diseases. We expect, on average, 300 new cases of breast cancer to be diagnosed each year in a cohort of 50,000 sisters aged 35-74 years. Thus, after five years of follow-up, we will have sufficient power, with about 1,500 new breast cancer cases, to address many key hypotheses regarding gene-environment interactions. Baseline questionnaires, banked blood, urine, and toenail samples, as well as banked environmental samples will provide a rich resource for testing current and future hypotheses regarding breast cancer risk. Follow-up questionnaires will update exposure and medical histories as well as provide an opportunity to collect new data and environmental samples to evaluate emerging hypotheses. Nested case-control or case-cohort analyses will be carried out among sisters who develop cancer and a sample of those who do not, to assess specific gene-environment interactions. Once assembled, the cohort also will provide the structure for assessing gene-environment interactions in risk for other diseases and will provide opportunities for add-on studies.
Title:Molecular Biomarkers for Assessing Breast Cancer Risk in Lactating Women
Summary: Accurate assessment of breast-cancer-risk will benefit most women and analysis of promoter hypermethylation in exfoliated epithelial cells in breast milk provides an ideal opportunity to assess breast-cancer-risk. We propose to examine breast milk samples from lactating women who are scheduled for a breast biopsy. About 10% of such women will have breast cancer; the remaining 90% will have benign lesions. Methylation analysis of epithelial cells in milk samples from each breast, will allow us to compare the promoter methylation in the diseased and the non-diseased breast of each woman. In addition, using the pathology reports and questionnaire data, we can compare methylation patterns between women with cancer and those without malignancy. Importantly, since 90% of our samples will come from women with benign disease, we can examine the relationship between promoter methylation patterns and breast-cancer-risk as defined by type of lesion, family history, and other risk factors.
The goal of this research is to develop a noninvasive molecular tool that can be used to accurately assess a woman’s risk of developing breast cancer. Our hypothesis is that epithelial cells isolated from breast milk can serve as a sensitive and reliable tool for assessing breast-cancer-risk.
We will collect breast milk samples from 250 women scheduled for a breast biopsy. Milk samples will be collected from each breast of each woman prior to her biopsy. Pathology report and questionnaire data (risk factors including reproductive history, health history, family cancer history etc,) will also be obtained. The promoter methylation pattern in a panel of genes known to exhibit promoter hypermethylation in breast cancer will be examined. DNA from the epithelial cells (positive selection with immunomagnetic beads) and from the non-epithelial cells (negative fraction containing blood, immune and other cells) will be isolated and after bisulfite treatment and gene specific amplification will analyzed by pyrosequencing. We will compare the milk epithelial methylation scores between 1) malignant disease and contralateral breasts, 2) benign lesion and contralateral breasts, 3) malignant disease and benign lesion breasts, 4) benign lesions with different risk factors, 5) validate comparisons with contralateral breasts through controls not scheduled for biopsy. Finally, milk fat, skim milk, and RNA will be archived for future studies of pollutant load, proteomics and gene expression, respectively.
Coming Soon:
Title: Development of Exercise and Dietary Interventions
Summary: Obesity is a complex phenotype resulting from interactions between genetics, diet, hormones, physical activity and environmental factors. Adulthood weight gain and obesity raises breast cancer risk after menopause and increases the likelihood of an adverse prognosis among women already diagnosed with breast cancer. The purpose of this research is to pilot test interventions that are linked to a lowered risk of recurrence and mortality among women already diagnosed with breast cancer and a lower risk of developing breast cancer among postmenopausal women. To better understand the conduct of these interventions, we propose a 12-week pilot intervention study to investigate whether interventions that contain both dietary and exercise components designed to reduce body weight affect body composition, hormones and biomarkers in apparently healthy postmenopausal women. We plan to use the findings from the pilot study to assist with funding application, design and implementation of a dietary and exercise intervention in postmenopausal breast cancer survivors and postmenopausal high-risk women.
Title: Analysis of Parity-Induced Protection in Human Breast and Serum
Summary: These proposed studies will focus on the analysis human breast tissue and blood to gain a better understanding of mechanisms underlying parity-related breast cancer protection resulting from early pregnancy. Breast tissue and blood from early-parous, late-parous, and nulliparous women will be collected. RNA and proteins will be isolated from whole blood and breast tissue and used for microarray and proteomic analyses to identify differentially expressed genes and proteins. We hope to find differences in the transcriptome and proteome of parous women compared to nulliparous women. Results will be used to identify biomarkers for breast cancer risk and develop strategies to protect the breast from carcinogenesis.
