Abstract
MicroRNAs (miRNAs) are small non-protein-coding RNA molecules that regulate gene expression. Diet and lifestyle factors have been hypothesized to be involved in the regulation of miRNA expression. In this study it was hypothesized that diet and lifestyle factors are associated with miRNA expression. Data from 1,447 cases of colorectal cancer to evaluate 34 diet and lifestyle variables using miRNA expression in normal colorectal mucosa as well as for differential expression between paired carcinoma and normal tissue were used. miRNA data were obtained using an Agilent platform. Multiple comparisons were adjusted for using the false discovery rate q-value. There were 250 miRNAs differentially expressed between carcinoma and normal colonic tissue by level of carbohydrate intake and 198 miRNAs differentially expressed by the level of sucrose intake. Of these miRNAs, 166 miRNAs were differentially expressed for both carbohydrate intake and sucrose intake. Ninety-nine miRNAs were differentially expressed by the level of whole grain intake in normal colonic mucosa. Level of oxidative balance score was associated with 137 differentially expressed miRNAs between carcinoma and paired normal rectal mucosa. Additionally, 135 miRNAs were differentially expressed in colon tissue based on recent NSAID use. Other dietary factors, body mass index, waist and hip circumference, and long-term physical activity levels did not alter miRNA expression after adjustment for multiple comparisons. These results suggest that diet and lifestyle factors regulate miRNA level. They provide additional support for the influence of carbohydrate, sucrose, whole grains, NSAIDs, and oxidative balance score on colorectal cancer risk.
Acknowledgments
The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. The authors acknowledge Sandra Edwards for data oversight, Dr Bette Caan and the staff at the KPMCP for their contribution to data collection, Dr Wade Samowitz for miRNA slide review, Erica Wolff and Michael Hoffman for miRNA analysis, Brett Milash and the Bioinformatics Shared Resource of the Huntsman Cancer Institute and University of Utah for miRNA and mRNA bioinformatics data processing, and Daniel Pellatt for statistical assistance. This study was supported by NCI grants CA163683 and CA48998 from the National Cancer Institute at the National Institutes of Health.
Author contributions
MLS designed research; RW and MLS conducted research; JSH, LEM, and JRS analyzed data and performed statistical analysis; MLS wrote paper and had primary responsibility for the final content; all authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.
Disclosure
The authors report no conflicts of interest in this work.