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Am J Cancer Res. 2015 Jun 15;5(7):2301-7. eCollection 2015.

Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence cervical cancer development.

Author information

1
National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Beijing, China ; Department of Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Zhengzhou, China.
2
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University Nanjing, China.
3
National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Beijing, China.
4
Department of Clinical Laboratory, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Beijing, China.
5
Department of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Beijing, China.
6
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University Nanjing, China ; State Key Laboratory of Reproductive Medicine, Nanjing Medical University Nanjing, China.

Abstract

Zinc ribbon domain containing 1 (ZNRD1) may play integral roles in immune response against HPV infection and cervical cancer. Its antisense transcript, ZNRD1-AS1, is an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. So we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence the susceptibility of cervical cancer through influencing ZNRD1 expression. We designed a population-based case-control study containing 1486 cervical cancer patients and 1536 controls to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and rs9261204) in ZNRD1-AS1 with the risk of cervical cancer. Logistic regression analyses in additive genetic model showed that all the three eQTLs SNPs decreased the risk of cervical cancer. Compared with those carrying "0" variant allele, subjects carrying "1-6" variant alleles had a 20% decreased risk of cervical cancer. Moreover, the haplotype containing variant alleles of these three SNPs significantly decreased the risk of cervical cancer when compared with the most frequent haplotype. In conclusion, ZNRD1 eQTLs SNPs in ZNRD1-AS1 could have a predisposition for the development of cervical cancer.

KEYWORDS:

ZNRD1; ZNRD1-AS1; cervical cancer; eQTLs

PMID:
26328261
PMCID:
PMC4548342

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