Abstract 4257: Dietary nutrient intake, ethnicity, and epigenetic silencing of lung cancer genes detected in sputum in New Mexican smokers

Abstract

Abstract Promoter hypermethylation of lung cancer (LC) genes detected in sputum assesses field cancerization and predicts LC risk. Hispanic smokers have greater risk for methylation than non-Hispanic Whites (NHW). We aimed to identify novel dietary nutrients affecting methylation of LC genes in sputum and determine the degree of ethnic disparity explained by diet. A cross-sectional population-based study was conducted with dietary intake assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1502 NHWs from the Lovelace Smokers cohort (LSC). Twelve LC genes with diverse cellular functions whose concomitant methylation strongly predicted LC risk were studied. A global association was identified between dietary intake and gene methylation (Ppermutation=0.003). Seventeen nutrient measurements were associated with methylation with magnitude greater than seen for folate and these nutrients together accounted for 36% of the variance in methylation. Six protective nutrients were identified and their insufficient intake in Hispanics explained approximately 42% of ethnic disparity in methylation. Functional validation of protective nutrients that also explained ethnic disparity was provided by showing an enhanced DNA repair capacity towards double-strand DNA breaks, a mechanistic biomarker strongly linked to acquisition of LC gene methylation in smokers. Dietary intake is a major modifiable factor for preventing promoter methylation of LC genes in smokers’ lungs. Altering the diet in Hispanics may alleviate ethnic disparity for methylation. Complex dietary supplements could be developed based on these protective nutrients for LC chemoprevention in smokers. This study was funded by NIH R01 CA097356, NIH/NCI P30 CA118100, and the State of New Mexico as a direct appropriation from the Tobacco Settlement Fund. Citation Format: Shuguang Leng, Maria Picchi, Piotr Filipczak, Frank Gilliland, Steven A. Belinsky. Dietary nutrient intake, ethnicity, and epigenetic silencing of lung cancer genes detected in sputum in New Mexican smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4257. doi:10.1158/1538-7445.AM2017-4257