Abstract 286: Epigenome-wide association study of normal lung tissues identifies hypomethylation of multiple CpG sites associated with cigarette smoking

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.286-286
• Main Authors: Li, Wen-Qing, Shi, Jianxin, Wheeler, William, Caporaso, Neil, Laird-Offspringa, Ite, Landi, Maria Teresa
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-286

Background: DNA methylation due to tobacco smoking have been reported in studies of blood genomic DNA, indicating a possible role of methylation changes due to smoking in multiple adverse health outcomes. Since DNA methylation is known to be tissue-specific, we profiled methylation in normal human lung tissues and evaluated the association with cigarette smoking based on a large sample size. Methods: We studied histologically normal lung tissues of 237 lung cancer patients (121 current cigarette smokers and 116 current nonsmokers) from the Environment And Genetics in Lung cancer Etiology study. DNA methylation was assayed using the Illumina Infinium HumanMethylation450 BeadChip arrays and methylation for 338,456 autosomal probes remained after quality control filters. We examined the association of log-transformed methylation with current smoking status, as well as with quantitative measures of smoking, using linear regression models adjusting for covariates. We sought to replicate the findings in The Cancer Genome Atlas normal lung samples (12 current smokers and 50 nonsmokers). Results: Eight CpG sites were significantly hypomethylated in lung tissues of current smokers after Bonferroni-correction (P