Abstract 4482: Effects of lifestyle modification on global DNA methylation in minority breast cancer survivors

Abstract

Abstract Changes in global DNA methylation are hypothesized to be a common biological mechanism in several diseases, including cancer. Specifically, measurements of global DNA methylation in peripheral tissues such as white blood cells are associated with an increased risk of several cancer types, asthma, autoimmune diseases and neurological disorders. Global DNA methylation biomarkers have been shown to respond to environmental and dietary exposures. Certain heavy metals, air pollutants, toxins, and lifestyle factors, such as alcohol consumption, diet, BMI and exercise, are associated with DNA methylation levels in blood. It has been hypothesized that DNA methylation is a biological mechanism by which alterations of lifestyle characteristics may modify cancer risk. In this study, we explored associations between three separate epigenetic biomarkers in peripheral blood and lifestyle modifications (diet, physical activity, weight loss, metabolic markers). Study participants were minority overweight and sedentary female breast cancer survivors (n=24) who participated in a larger randomized, crossover, pilot study of a 6-month dietary change, physical activity and weight loss intervention. Clinic visits were conducted at baseline, 6 months and 12 months with the following activities: fasting morning blood draw, anthropometric measures (height, weight), and completion of a food frequency questionnaire. Plasma samples were analyzed for metabolic markers (insulin, glucose). Percent DNA methylation was measured using the Luminometric methylation assay (LUMA), the MethylLight assay to determine Sat2 methylation, and pyrosequencing for LINE-1. Levels of LINE-1 DNA methylation were statistically significantly elevated at 6 months (75.5% vs. 78.5% [p<0.00001]) and 12 months (75.5% vs. 77.7% [p<0.00001]), compared to baseline. DNA methylation measured by LUMA and levels of Sat2 DNA methylation did not differ by timepoint. LUMA DNA methylation levels at baseline and 6 months were 69.6% and 70.7% (p=0.14), respectively; and Sat2 DNA methylation at baseline and 6 months was 91.3% and 103.3% (p=0.53), respectively. Generalized estimated equation models showed associations between increases in DNA methylation levels as measured by LUMA with increases in fruit/vegetable, fat and protein intake (ß=0.0118 [95% CI= 0.0018-0.0219], ß=0.0469 [95% CI= 0.0024-0.0914], and ß=0.0410 [95% CI= 0.0119-0.0702], respectively). A positive association was also found between LUMA DNA methylation and caloric intake and glucose levels (0.2371 [95% CI= 0.0356-0.4387] and 0.2371 [95% CI= 0.0356-0.4387], respectively). Overall our exploratory findings suggest that lifestyle interventions to change diet and metabolic markers may have measureable effects on blood DNA methylation levels. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4482. doi:1538-7445.AM2012-4482