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Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence cervical cancer development
Lanwei Guo1, Juan Wen2, Jing Han2
1National 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.
American Journal of Cancer Research
|September 2, 2015
Summary
Single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may influence cervical cancer risk. Specific SNPs (rs3757328, rs6940552, rs9261204) were associated with a decreased risk of cervical cancer in a population-based study.
Area of Science:
- Genetics
- Oncology
- Immunology
Background:
- Zinc ribbon domain containing 1 (ZNRD1) is implicated in immune responses to HPV infection and cervical cancer.
- ZNRD1-AS1, an antisense transcript, regulates ZNRD1 expression.
- Bioinformatics identified single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 as potential expression quantitative trait loci (eQTLs) for ZNRD1.
Purpose of the Study:
- To investigate the association between ZNRD1 eQTLs SNPs in ZNRD1-AS1 and cervical cancer susceptibility.
- To test the hypothesis that these eQTLs SNPs influence cervical cancer risk by modulating ZNRD1 expression.
Main Methods:
- A population-based case-control study was conducted with 1486 cervical cancer patients and 1536 controls.
- Logistic regression analysis was used to assess the association of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552, rs9261204) in ZNRD1-AS1 with cervical cancer risk.
- Haplotype analysis was performed to evaluate combined SNP effects.
Main Results:
- All three investigated eQTLs SNPs in ZNRD1-AS1 were associated with a decreased risk of cervical cancer under an additive genetic model.
- Individuals carrying variant alleles (1-6) of these SNPs showed a 20% reduced risk of cervical cancer compared to those with zero variant alleles.
- A haplotype composed of variant alleles of the three SNPs significantly lowered cervical cancer risk relative to the most frequent haplotype.
Conclusions:
- ZNRD1 eQTLs SNPs located within ZNRD1-AS1 may confer a predisposition to cervical cancer development.
- These genetic variations could impact cervical cancer susceptibility through their regulatory role on ZNRD1 expression.
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