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

被引：20

作者：

Peckham-Gregory, Erin C. ^{[1
]}

Thapa, Dharma R. ^{[2
,3
,4
,5
]}

Martinson, Jeremy ^{[6
]}

Duggal, Priya ^{[7
]}

Penugonda, Sudhir ^{[8
]}

Bream, Jay H. ^{[9
]}

Chang, Po-Yin ^{[1
]}

Dandekar, Sugandha ^{[10
]}

Chang, Shen-Chih ^{[1
]}

Detels, Roger ^{[1
]}

Martinez-Maza, Otoniel ^{[1
,11
,12
]}

Zhang, Zuo-Feng ^{[1
]}

Hussain, Shehnaz K. ^{[1
,13
,14
]}

机构：

[1] Univ Calif Los Angeles, Dept Epidemiol, Fielding Sch Publ Hlth, Box 951772,71-267 CHS, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Immunol, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Genet, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[6] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, 403 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA

[7] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, 615 North Wolfe St,Room E6539, Baltimore, MD 21205 USA

[8] Northwestern Univ, Div Infect Dis, Feinberg Sch Med, 645 North Michigan Ave,Suite 900, Chicago, IL 60611 USA

[9] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 North Wolfe St,Room E5624, Baltimore, MD 21205 USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, UCLA Genotyping & Sequencing Core, CHS 36-125,650 Charles E Young Dr South, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[12] Univ Calif Los Angeles, UCLA AIDS Inst, Box 951740,153 BSRB, Los Angeles, CA 90095 USA

[13] Cedars Sinai Med Ctr, Dept Med, 8700 Beverly Blvd, West Hollywood, CA 90048 USA

[14] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, 8700 Beverly Blvd, West Hollywood, CA 90048 USA

来源：

CANCER EPIDEMIOLOGY | 2016年 / 45卷

基金：

美国国家卫生研究院;

关键词：

DDX20; AIDS-NHL; microRNA; SNPs; microRNA-SNP; Lymphoma; Epidemiology; B-CELL LYMPHOMAS; SINGLE NUCLEOTIDE POLYMORPHISMS; HIV/HCV-COINFECTED PATIENTS; ANTIRETROVIRAL THERAPY ERA; CANCER-RISK; EPIDEMIOLOGIC RESEARCH; BAYESIAN PERSPECTIVES; GENETIC-VARIATIONS; BINDING-SITES; HIV-INFECTION;

D O I：

10.1016/j.canep.2016.09.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：47 / 57

页数：11

共 111 条

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