MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study

Erin C. Peckham-Gregory, Dharma R. Thapa, Jeremy Martinson, Priya Duggal, Sudhir Penugonda, Jay H. Bream, Po Yin Chang, Sugandha Dandekar, Shen Chih Chang, Roger Detels, Otoniel Martínez-Maza, Zuo Feng Zhang, Shehnaz K. Hussain

Research output: Contribution to journalArticle

Abstract

Background MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. Methods Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels. Results DDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR = 1.34 per minor allele; 95% CI: 1.02–1.75), and higher miRNA-222 serum levels nearing statistical significance (MR = 1.21 per minor allele; 95% CI: 0.98–1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR = 0.52; 95% CI: 0.27–0.99). The minor allele of HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR = 1.73 per minor allele; 95% CI: 1.12–2.67), and decreased CNS AIDS-NHL risk (OR = 0.49 per minor allele; 95% CI: 0.25–0.94). Conclusions This study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalCancer Epidemiology
Volume45
DOIs
StatePublished - Dec 1 2016

Keywords

  • AIDS-NHL
  • DDX20
  • Epidemiology
  • Lymphoma
  • SNPs
  • microRNA
  • microRNA-SNP

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research

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    Peckham-Gregory, E. C., Thapa, D. R., Martinson, J., Duggal, P., Penugonda, S., Bream, J. H., Chang, P. Y., Dandekar, S., Chang, S. C., Detels, R., Martínez-Maza, O., Zhang, Z. F., & Hussain, S. K. (2016). MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study. Cancer Epidemiology, 45, 47-57. https://doi.org/10.1016/j.canep.2016.09.007