Abstract
PURPOSE: Alcohol consumption has been purported to influence many diseases. MicroRNAs (miRNAs) may be influenced by compounds found in alcohol. In this investigation, we test the hypothesis that total alcohol, beer, wine, and hard liquor influence miRNA expression. METHODS: We studied 1447 colorectal (CR) cancer cases with normal CR mucosa and carcinoma miRNA expression data along with alcohol consumption data. We analyzed long-term and long-term and current (LTC) alcohol use for beer, liquor, and wine with miRNA expression between paired carcinoma and normal colon and rectal tissues, adjusting for multiple comparisons using the positive false discovery rate q-value. MiRNAs associated significantly with alcohol were examined with all-cause mortality (ACM). MiRNAs associated significantly with ACM were examined with RNA-Seq data. RESULTS: Expression of 84 miRNAs was associated significantly with LTC wine use in normal rectal mucosa. Higher expression of two of these miRNAs significantly worsened ACM: hsa-miR-210 (Hazard Ratio [HR] 1.12, 95% CI (1.03, 1.21), p-value = 0.004), and hsa-miR-92a-1-5p (HR 1.20, 95% CI (1.04, 1.38), p-value = 0.013). These miRNAs were downregulated across levels of LTC wine consumption. CONCLUSIONS: Our results suggest that wine influences miRNA expression in rectal cancer, supporting the hypothesis that components in alcohol influence miRNA expression.