Dietary Nutrient Intake, Ethnicity, and Epigenetic Silencing of Lung Cancer Genes Detected in Sputum in New Mexican Smokers

Abstract

Lung cancer gene methylation detected in sputum assesses field cancerization and predicts lung cancer incidence. Hispanic smokers have higher lung cancer susceptibility compared with non-Hispanic whites (NHW). We aimed to identify novel dietary nutrients affecting lung cancer gene methylation and determine the degree of ethnic disparity in methylation explained by diet. Dietary intakes of 139 nutrients were assessed using a validated Harvard food frequency questionnaire in 327 Hispanics and 1,502 NHWs from the Lovelace Smokers Cohort. Promoter methylation of 12 lung cancer genes was assessed in sputum DNA. A global association was identified between dietary intake and gene methylation ( = 0.003). Seventeen nutrient measurements were identified with magnitude of association with methylation greater than that seen for folate. A stepwise approach identified B12, manganese, sodium, and saturated fat as the minimally correlated set of nutrients whose optimal intakes could reduce the methylation by 36% ( < 0.001). Six protective nutrients included vitamin D, B12, manganese, magnesium, niacin, and folate. Approximately 42% of ethnic disparity in methylation was explained by insufficient intake of protective nutrients in Hispanics compared with NHWs. Functional validation of protective nutrients showed an enhanced DNA repair capacity toward double-strand DNA breaks, a mechanistic biomarker strongly linked to acquisition of lung cancer gene methylation in smokers. Dietary intake is a major modifiable factor for preventing promoter methylation of lung cancer genes in smokers' lungs. Complex dietary supplements could be developed on the basis of these protective nutrients for lung cancer chemoprevention in smokers. Hispanic smokers may benefit the most from this complex for reducing their lung cancer susceptibility. .

Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

“…Stidley et al had identified folate, leafy green vegetables, and multi-vitamin use as three protective factors against acquisition of gene methylation in lungs of non-Hispanic whites [ 102 ]. Later in the same cohort, another five factors including vitamin D, B 12 , manganese, magnesium, and niacin were also identified as protective nutrients against gene methylation [ 103 ]. A nested case-control study found that serum folate was associated with increased methylation levels of ras association domain family 1 isoform A (RASSF1A) and methylene tetrahydrofolate reductase (MTHFR), while methionine showed an inverse association with that of RASSF1A [ 104 ].…”

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust

“…Second, the difference of magnitude of the association between models with (c′) and without (c) adjustment for potential mediators (Fig. 3 A) was calculated to quantify the mediation effect of mediators on the association between diesel exhaust exposure and HCAECs activation [ 47 ]. A permutation-based method was used to assess whether the proportion mediated was statistically significant or not and was detailed in figure legend of Fig.…”

How Dietary Factors Affect DNA Methylation: Lesson from Epidemiological Studies

“…Interestingly, they noted that high intake of green vegetables and folate was associated with lower DNA methylation, expressed as less than two genes methylated [51]. A prospective analysis on the same cohort further demonstrated both positive (saturated fat) and negative (vitamin A, folate, and vitamin D) associations of dietary factors with DNA methylation of twelve cancer genes [52].…”