Influence of Quercetin-Rich Food Intake on microRNA Expression in Lung Cancer Tissues

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 21; no. 12; pp. 2176 - 2184
• Main Authors: LAM, Tram K, SHAO, Stephanie, YINGDONG ZHAO, MARINCOLA, Francesco, PESATORI, Angela, BERTAZZI, Pier Alberto, CAPORASO, Neil E, ENA WANG, LANDI, Maria Teresa
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2012
• Subjects: Adenocarcinoma - epidemiology; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma of Lung; Aged; Biological and medical sciences; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Case-Control Studies; Diet; Female; Formaldehyde; Humans; Italy - epidemiology; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Medical sciences; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Paraffin Embedding; Pneumology; Quercetin - administration & dosage; Risk Factors; Tissue Fixation; Tumors; Tumors of the respiratory system and mediastinum; Italy; Lung disease; RNA interference; Respiratory disease; Lung cancer; Micro RNA; Malignant tumor; Flavonoid; Gene silencing; Tissue; Polyphenol; Cancerology; Food intake; Quercetin; Phenols; Bronchus disease; Cancer
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-12-0745

Epidemiologic studies have reported that frequent consumption of quercetin-rich foods is inversely associated with lung cancer incidence. A quercetin-rich diet might modulate microRNA (miR) expression; however, this mechanism has not been fully examined. miR expression data were measured by a custom-made array in formalin-fixed paraffin-embedded tissue samples from 264 lung cancer cases (144 adenocarcinomas and 120 squamous cell carcinomas). Intake of quercetin-rich foods was derived from a food-frequency questionnaire. In individual-miR-based analyses, we compared the expression of miRs (n = 198) between lung cancer cases consuming high versus low quercetin-rich food intake using multivariate ANOVA tests. In family-miR-based analyses, we used Functional Class Scoring (FCS) to assess differential effect on biologically functional miR families. We accounted for multiple testing using 10,000 global permutations (significance at P(global) < 0.10). All multivariate analyses were conducted separately by histology and by smoking status (former and current smokers). Family-based analyses showed that a quercetin-rich diet differentiated miR expression profiles of the tumor suppressor let-7 family among adenocarcinomas (P(FCS) < 0.001). Other significantly differentiated miR families included carcinogenesis-related miR-146, miR-26, and miR-17 (P (FCS) < 0.05). In individual-based analyses, we found that among former and current smokers with adenocarcinoma, 33 miRs were observed to be differentiated between highest and lowest quercetin-rich food consumers (23 expected by chance; P(global) = 0.047). We observed differential expression of key biologically functional miRs between high versus low consumers of quercetin-rich foods in adenocarcinoma cases. Our findings provide preliminary evidence on the mechanism underlying quercetin-related lung carcinogenesis.