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

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

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.

MeSH terms

  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Haplotypes
  • Humans
  • Logistic Models
  • PAX8 Transcription Factor / genetics*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • RNA, Long Noncoding / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • PAX8 Transcription Factor
  • PAX8 protein, human
  • RNA, Long Noncoding
  • long non-coding RNA PAX8-AS1, human