Epigenomics of Neurocognitive Function in Breast Cancer

This study harnessed the data and biospecimens from the Exercise Program in Cancer and Cognition (EPICC) study (parent study) that collected data on cognitive function, demographics, other symptoms and biospecimens at two time points (T1: enrollment, T2: six months later) within the context of a six-month randomized controlled trial of a moderate intensity aerobic exercise intervention. This study collected genome wide DNA methylation data from T1 and T2 and conducted epigenome-wide association-based analyses to find genes and biological pathways explaining variability in cognitive function and explaining how exercise mitigates cognitive decline. Our initial findings identified cg10331779 near CTNND2 (p-value=9.65×10-9) associated with processing speed and cg25906741 in MLIP (p-value=2.01×10-8) associated with subjectively measured cognitive function. Additionally, differentially methylated regions were identified near SLC6A11, PRKG1/CSTF2T, and FAM3B for processing speed and near PI4KB and SGCE/PEG10 for mental flexibility. ]]>
Inclusion Criteria (All Participants):Postmenopausal women; Maximum 80 years of age; Able to speak and read English; A minimum of 8 years of education; Diagnosed with hormone-receptor positive, stage I, II, or IIIa breast cancer, confirmed by their medical oncologist; Will receive AI therapy; Medical clearance by their breast cancer surgeon; Intention to remain in the local area during the duration of the exercise program. Exclusion Criteria (All Participants):Prior diagnosis of cancer; Already meeting >50% of physical activity recommendations as measured by the Physical Activity Scale for the Elderly (PASE); Clinical evidence of distant metastases including the central nervous system and bone metastasis; Any breast cancer surgery complications including persistent seroma requiring aspiration, wound dehiscence, infection, prolonged drain output, lymphedema; Reconstructive surgery; A medical condition that would preclude them from exercising including a history of coronary artery or pulmonary disease; Current hormone replacement therapy use; Current treatment for Type II Diabetes (participation in regular exercise would require close monitoring of medication dose); Eating disorders or a history of substance abuse; Self-report of hospitalization for psychiatric illness within the last two years; History of neurologic illness such as stroke, multiple sclerosis, Parkinson's disease, dementia, or chronic fatigue syndrome; Any use of an assisted walking device Additional Exclusion Criteria (Neuroimaging Subgroup):Presence of metal implants (i.e., pacemaker, some stents); Claustrophobia ]]>