Influence of quercetin-rich food intake on microRNA expression in lung cancer tissues

Tram K. Lam, Stephanie Shao, Yingdong Zhao, Francesco Marincola, Angela Pesatori, Pier Alberto Bertazzi, Neil E. Caporaso, Ena Wang, Maria Teresa Landi

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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 Pglobal < 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 (PFCS < 0.001). Other significantly differentiated miR families included carcinogenesis-related miR-146, miR-26, and miR-17 (PFCS < 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; Pglobal = 0.047). Conclusions: We observed differential expression of key biologically functional miRs between high versus low consumers of quercetin-rich foods in adenocarcinoma cases. Impact: Our findings provide preliminary evidence on the mechanism underlying quercetin-related lung carcinogenesis.

Original languageEnglish
Pages (from-to)2176-2184
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number12
DOIs
Publication statusPublished - 1 Dec 2012

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Lam, T. K., Shao, S., Zhao, Y., Marincola, F., Pesatori, A., Bertazzi, P. A., Caporaso, N. E., Wang, E., & Landi, M. T. (2012). Influence of quercetin-rich food intake on microRNA expression in lung cancer tissues. Cancer Epidemiology Biomarkers and Prevention, 21(12), 2176-2184. https://doi.org/10.1158/1055-9965.EPI-12-0745