Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival

Weikang Zhang, Hongliang Liu, Jieyun Yin, Wenting Wu, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, Yi Li, Jiali Han, Qingyi Wei

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The Piwi-piRNA pathway is important for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control and thus may be involved in cancer development. In this study, we comprehensively analyzed prognostic roles of 3,116 common SNPs in PIWI-piRNA pathway genes in melanoma disease-specific survival. A published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used to identify associated SNPs, which were later validated by another GWAS from the Harvard Nurses' Health Study and Health Professionals Follow-up Study. After multiple testing correction, we found that there were 27 common SNPs in two genes (PIWIL4 and DCP1A) with false discovery rate < 0.2 in the discovery dataset. Three tagSNPs (i.e., rs7933369 and rs508485 in PIWIL4; rs11551405 in DCP1A) were replicated. The rs11551405 A allele, located at the 3' UTR microRNA binding site of DCP1A, was associated with an increased risk of melanoma disease-specific death in both discovery dataset [adjusted Hazards ratio (HR) = 1.66, 95% confidence interval (CI) = 1.21–2.27, p =1.50 × 10−3] and validation dataset (HR = 1.55, 95% CI = 1.03–2.34, p = 0.038), compared with the C allele, and their meta-analysis showed an HR of 1.62 (95% CI, 1.26–2.08, p =1.55 × 10−4). Using RNA-seq data from the 1000 Genomes Project, we found that DCP1A mRNA expression levels increased significantly with the A allele number of rs11551405. Additional large, prospective studies are needed to validate these findings.

Original languageEnglish (US)
Pages (from-to)2730-2737
Number of pages8
JournalInternational Journal of Cancer
Volume139
Issue number12
DOIs
StatePublished - Dec 15 2016

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Keywords

  • Cox regression
  • PIWI-piRNA pathway
  • cutaneous melanoma
  • disease specific survival
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, W., Liu, H., Yin, J., Wu, W., Zhu, D., Amos, C. I., Fang, S., Lee, J. E., Li, Y., Han, J., & Wei, Q. (2016). Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival. International Journal of Cancer, 139(12), 2730-2737. https://doi.org/10.1002/ijc.30409