Abstract 1068: Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue

Abstract

Abstract Aberrant DNA methylation in peripheral blood cells (PBCs) may be a potential noninvasive biomarker for breast cancer risk. Whether methylations at CpG sites in PBCs can serve as proxies in normal breast tissues are unknown. We evaluated the correlation of DNA methylation between PBC DNA and breast cancer adjacent normal tissue using data and samples from the Shanghai Breast Cancer Study. Genome-wide DNA methylation profiles in PBCs and matched tumor adjacent normal tissues from 31 breast cancer patients were assayed using Illumina HumanMethylation450 BeadChip, which includes >485,000 CpG sites and covers 99% of RefSeq genes with multiple probes per gene. After quality control filtering, a total of 432,513 CpG sites were retained for analysis. We evaluated the association of methylation for each CpG site between DNA samples for PBCs and normal breast tissue using Spearman's rank correlation (r). The overall median correlation (r) is 0.35. A total of 99,928 (23.1%) and 18,290 (4.2%) of CpG sites had a high correlation between PBC DNA and normal breast tissue DNA with r > 0.50 and r > 0.75, respectively. Interestingly, we found that the correlation was negatively associated with both methylation levels (mean) and inter-person variability (standard deviation) in normal breast tissues (ρ = -0.14 and -0.19; P < 2.2 x10-16 for both). In 926 previously reported methylation quantitative trait loci, the correlations between PBCs and normal breast tissue were significantly higher (median r = 0.42) than the remaining loci (median r = 0.34) (Wilcoxon test, P < 2.2 x10-16), suggesting that methylation variations controlled by genetic variations exhibited a robust correlation between PBC and normal breast tissue DNA. In summary, our results suggest that the methylation status of CpG sites with large inter-person variations or genetically-controlled variations in PBC DNA correlate well with those in normal breast tissue. This supports the conduct of a genome-wide methylation study for breast cancer using PBC DNA. Citation Format: Xingyi Guo, Xiao-Ou Shu, Chun Li, Jirong Long, Bingshan Li, Yu-Tang Gao, Wei Zheng, Qiuyin Cai. Correlation of DNA methylation pattern between peripheral blood cell and normal breast tissue. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1068. doi:10.1158/1538-7445.AM2015-1068