title: Influence of quercetin-rich food intake on microRNA expression in lung cancer tissues.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  We observed differential expression of key biologically functional miRs between high versus low consumers of quercetin-rich foods in adenocarcinoma cases.
  
  
  CONCLUSIONS
  Our findings provide preliminary evidence on the mechanism underlying quercetin-related lung carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Tram K
authors.initials: TK
authors.lastname: Lam
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shao
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.forename: Angela
authors.initials: A
authors.lastname: Pesatori
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016612:Paraffin Embedding; D011794:Quercetin / Q000008:administration & dosage*; D012307:Risk Factors; D016707:Tissue Fixation
chemical_list: D035683:MicroRNAs; D005557:Formaldehyde; D011794:Quercetin