Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers

BMC Medical Genomics

Sarah A Tishkoff²  Michael C Campbell³  Renata A Rawlings-Goss¹ 

[1]Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA

[2]Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA

[3]Department of Biostatistics, Yale University, New Haven, CT 06520, USA

关键词: Diabetes;    Cancer;    Disease susceptibility;    African genetic diversity;    Whole-genome sequencing;    Population differentiation;    Biomarkers;    miRNA;   

Others  :  1090498
DOI  :  10.1186/1755-8794-7-53

 received in 2014-05-05, accepted in 2014-08-12,  发布年份 2014

【 摘 要 】

Background

MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes.

Methods

Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations.

Results

We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10⁻⁷), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality.

Conclusion

MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in part to health disparities observed in multiple forms of cancer, specifically breast cancer, and will be an essential consideration when assessing the utility of miRNA biomarkers for the clinic.

【 授权许可】

   
2014 Rawlings-Goss et al.; licensee BioMed Central Ltd.

【 图 表 】

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