Abstract 5615: Global DNA methylation by LUMA predicts breast cancer risk in a population-based study

Abstract

Abstract Global methylation dysregulation is a hallmark of cancer cells. Global methylation measurement in peripheral blood may be a predictor of cancer risk and prognosis. In this study, we used two independent assays, LUminometric Methylation Assay (LUMA) and LINE-1 methylation by pyrosequencing, to assess the global methylation content in the peripheral blood DNA from the Long Island Breast Cancer Study Project, a population-based case-control study. We examined the association between global methylation levels and: 1) the risk of developing breast cancer among 1055 cases and 1101 controls using logistic regression models; 2) the risk of mortality among breast cancer cases using Cox proportional hazards models; and 3) one-carbon metabolism genetic polymorphisms and dietary intake among controls using ANOVA. LUMA methylation levels were higher among cases (mean: 57.3%) than among controls (mean: 52.4%; p<0.001). Compared to women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increase in the risk of developing breast cancer (95% CI: 1.83-3.16; p for trend < 0.0001). Risk was strongest for in situ breast cancer (OR: 6.18; 95% CI: 3.34-11.43), although the estimate is based on small numbers; but the association did not vary by other tumor characteristics, life-style or several established breast cancer risk factors. Among cases, there was an indication that high LUMA levels were associated with reduced breast cancer-specific mortality. Among controls, LUMA levels were associated with two SNPs in the one-carbon metabolism pathway, MTHFR C677T (p=0.001) and MTRR A66G (p=0.018), but not with dietary intake of one-carbon related nutrients. No association was observed between LINE-1 methylation and breast cancer risk, breast cancer-specific mortality, one-carbon metabolism SNPs or nutrients, or LUMA methylation. Our results suggest that LUMA methylation levels in peripheral blood DNA are associated with breast cancer development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5615. doi:10.1158/1538-7445.AM2011-5615