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Mol Genet Genomics. 2016 Aug;291(4):1743-8. doi: 10.1007/s00438-016-1217-9. Epub 2016 May 25.

Expression quantitative trait loci in long non-coding RNA PAX8-AS1 are associated with decreased risk of cervical cancer.

Han J1,2, Zhou W1, Jia M1, Wen J1, Jiang J1, Shi J3, Zhang K4, Ma H1,5, Liu J6, Ren J3, Dai M3, Hu Z1,5, Hang D7, Li N8, Shen H9,10.

Author information

1
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Department of Epidemiology and Biostatistics, School of Public Health, Cancer Center, Nanjing Medical University, Nanjing, 211166, China.
2
Department of Epidemiology, Nanjing Medical University Affiliated Cancer Institute of Jiangsu Province, Nanjing, China.
3
National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, China.
4
Department of Cancer Prevention, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
5
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
6
Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
7
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Department of Epidemiology and Biostatistics, School of Public Health, Cancer Center, Nanjing Medical University, Nanjing, 211166, China. hangdong@njmu.edu.cn.
8
National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, No. 17 Panjiayuannanli, Chaoyang District, Beijing, China. lini1240@hotmail.com.
9
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Department of Epidemiology and Biostatistics, School of Public Health, Cancer Center, Nanjing Medical University, Nanjing, 211166, China. hbshen@njmu.edu.cn.
10
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. hbshen@njmu.edu.cn.

Abstract

Paired box 8 (PAX8) is a crucial nephric-lineage transcription factor, and its aberrant expression has been detected in various types of cancer including Müllerian carcinomas. PAX8 antisense RNA 1 (PAX8-AS1), a potential regulator of PAX8, contains specific single nucleotide polymorphisms (SNPs) that may represent expression quantitative trait loci (eQTLs) for PAX8. In this study, we hypothesized that these eQTLs SNPs in PAX8-AS1 may influence the risk of cervical cancer. A case-control study of 1486 cervical cancer patients and 1536 cancer-free controls was conducted to identify the associations between two eQTLs SNPs (rs4848320 and rs1110839) and cervical cancer. Logistic regression analyses revealed that variant allele T of rs4848320 (recessive model: adjusted OR = 0.61, 95 % CI = 0.38-0.97, P = 0.027) and G of rs1110839 (additive model: adjusted OR = 0.88, 95 % CI = 0.79-0.99, P = 0.032) were associated with decreased risk of cervical cancer. Moreover, the haplotype containing variant alleles of the two SNPs significantly decreased the risk of cervical cancer compared to the most frequent haplotype (adjusted OR = 0.82, 95 % CI = 0.70-0.95, P = 0.009). These findings indicate that PAX8 eQTLs SNPs may serve as novel susceptibility markers for cervical cancer.

KEYWORDS:

Cervical cancer; LncRNA; PAX8; PAX8-AS1; Single nucleotide polymorphism

PMID:
27225188
DOI:
10.1007/s00438-016-1217-9
[Indexed for MEDLINE]

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