Abstract
To examine DNA methylation as a mechanism linking diet, physical activity, weight status, and breast cancer risk. Insufficiently active women of varying weight status, without a history of cancer, completed a maximal exercise test, clinical measurement of height and weight, and a dietary intake measure. They also provided blood samples, which were analyzed to ascertain average methylation of candidate genes related to breast cancer (BRCA1, RUNX3, GALNT9, and PAX6) and inflammation (TLR4 and TLR6). Elevated weight status (r=-.18, p<.05) and poorer aerobic fitness (r=.24, p<.01) were each associated with decreased methylation of inflammation genes. Methylation of inflammation genes statistically mediated the relationship between weight status and cancer gene methylation (standardized indirect effect=.12, p<.05) as well as between cardiorespiratory fitness and cancer gene methylation (standardized indirect effect=-.172, p<.01). However, recent dietary behavior was not associated with methylation of either inflammation or cancer genes. Both weight status and cardiovascular fitness are associated with methylation of genes associated with both inflammation and cancer. Methylation of inflammatory genes might serve as a mechanistic link between lifestyle factors and methylation changes in genes that increase risk for breast cancer.
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