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

doi:10.1016/j.canep.2016.09.007

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

Cancer Epidemiol. 2016 Dec:45:47-57. doi: 10.1016/j.canep.2016.09.007. Epub 2016 Oct 1.

Authors

Affiliations

¹ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA. Electronic address: Erin.Peckham@bcm.edu.
² Departments of Obstetrics and Gynecology, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA.
³ Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, 403 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA.
⁴ Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Room E6539, Baltimore, MD 21205, USA.
⁵ Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, 645 North Michigan Avenue, Suite 900, Chicago, IL 60611, USA.
⁶ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Room E5624, Baltimore, MD 21205, USA.
⁷ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA.
⁸ The UCLA Genotyping and Sequencing Core, Department of Human Genetics, David Geffen School of Medicine, UCLA, CHS 36-125, 650 Charles E Young Drive South, Los Angeles, CA 90095, USA.
⁹ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA; Departments of Obstetrics and Gynecology, and Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA; Jonsson Comprehensive Cancer Center, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA; UCLA AIDS Institute, UCLA, Box 951740, 153 BSRB, Los Angeles, CA 90095-1740, USA.
¹⁰ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), Box 951772, 71-267 CHS, Los Angeles, CA 90095-1772, USA; Department of Medicine and Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd, West Hollywood, CA 90048, USA.

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.

Keywords: AIDS-NHL; DDX20; Epidemiology; Lymphoma; SNPs; microRNA; microRNA-SNP.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Case-Control Studies
Cohort Studies
Female
Genetic Predisposition to Disease*
Humans
Lymphoma, AIDS-Related / genetics*
Male
MicroRNAs / genetics*
Middle Aged
Polymorphism, Single Nucleotide*

Substances

MicroRNAs

Abstract

Publication types

MeSH terms

Substances

Grants and funding