Several established risk factors such as age, parity, family history and body mass index (BMl) contribute to the genesis of invasive breast cancers, the most common non-keratinocyte cancer among women in the United States. The current model of breast cancer indicates progression from normal breast to a benign lesion, noninvasive disease, and then an invasive tumor. Relationships between established breast cancer risk factors and the epigenetic character of breast tumors have begun to be described, and epigenetic alterations including DNA methylation alterations are known early contributors to breast tumorigenesis. However, the presence of epigenetic alterations that occur in the context of invasive breast cancer is underexplored along the continuum of normal breast, pre-neoplastic lesions, and non-invasive breast cancers. Our published preliminary data indicate significant, independent associations of breast tumor DNA methylation profiles with modifiable breast cancer risk factors. Here, we propose to test the hypothesis that DNA methylation variation in normal breast, pre-neoplastic lesions, and non-invasive cancers is associated with disease risk factors and progression to invasive disease. This work will leverage existing tissue and patient data resources from women enrolled in the New Hampshire Mammography Network allowing investigation of DNA methylation in benign lesions and pre-invasive disease. In addition, we will study women of child-bearing age through the New Hampshire Birth Cohort Study, collecting non-neoplastic cells from breast milk and nipple aspirate fluid to evaluate the relationships between DNA methylation and risk factors for breast cancer. Further, we will explore intraindividual changes in DNA methylation from repeated collections of breast milk and nipple aspirate fluid in a subset of women. The goal of this work is to extend our understanding of the biological mechanisms through which established breast cancer risk factors contribute to carcinogenesis, which has broad potential to impact all individuals at risk for breast cancer by better directing existing risk prediction models, and informing novel strategies for breast cancer prevention.
Breast cancer Is the most common non-keratinocyte cancer among women. Our proposal will characterize the relationships between risk factors for invasive breast cancer and epigenetic alterations in pre-cancerous and non-invasive breast tissues to extend our understanding of breast carcinogenesis and inform novel strategies for disease prevention.
|Nachman, Keeve E; Punshon, Tracy; Rardin, Laurie et al. (2018) Opportunities and Challenges for Dietary Arsenic Intervention. Environ Health Perspect 126:84503|
|Moen, Erika L; Bynum, Julie P; Austin, Andrea M et al. (2018) Assessing Variation in Implantable Cardioverter Defibrillator Therapy Guideline Adherence With Physician and Hospital Patient-sharing Networks. Med Care 56:350-357|
|Braun, Joseph M; Chen, Aimin; Hoofnagle, Andrew et al. (2018) Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels. Horm Behav 101:77-84|
|Punshon, Tracy; Jackson, Brian P (2018) Essential micronutrient and toxic trace element concentrations in gluten containing and gluten-free foods. Food Chem 252:258-264|
|El-Jawahri, Areej; Fishman, Sarah R; Vanderklish, Julie et al. (2018) Pilot study of a multimodal intervention to enhance sexual function in survivors of hematopoietic stem cell transplantation. Cancer 124:2438-2446|
|El-Jawahri, Areej; Nelson-Lowe, Margaret; VanDusen, Harry et al. (2018) Patient-Clinician Discordance in Perceptions of Treatment Risks and Benefits in Older Patients with Acute Myeloid Leukemia. Oncologist :|
|Cai, Yunliang; Wu, Shaoju; Zhao, Wei et al. (2018) Concussion classification via deep learning using whole-brain white matter fiber strains. PLoS One 13:e0197992|
|White, Alexandra J; O'Brien, Katie M; Jackson, Brian P et al. (2018) Urine and toenail cadmium levels in pregnant women: A reliability study. Environ Int 118:86-91|
|Passarelli, M N; Barry, E L; Zhang, D et al. (2018) Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic acid for the prevention of colorectal adenomas. Br J Dermatol 179:337-344|
|Felix, Janine F; Joubert, Bonnie R; Baccarelli, Andrea A et al. (2018) Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol 47:22-23u|
Showing the most recent 10 out of 131 publications