title: Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival.
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.
authors: Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.|Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Weikang
authors: W
authors: Zhang
authors: Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
authors: Hongliang
authors: H
authors: Liu
authors: Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.|Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
authors: Jieyun
authors: J
authors: Yin
authors: Department of Epidemiology, Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
authors: Wenting
authors: W
authors: Wu
authors: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
authors: Dakai
authors: D
authors: Zhu
authors: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
authors: Christopher I
authors: CI
authors: Amos
authors: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Shenying
authors: S
authors: Fang
authors: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors: Jeffrey E
authors: JE
authors: Lee
authors: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
authors: Yi
authors: Y
authors: Li
authors: Department of Epidemiology, Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana. qingyi.wei@duke.edu.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. qingyi.wei@duke.edu.
authors: Jiali
authors: J
authors: Han
authors: Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina. jialhan@iu.edu.
authors: Qingyi
authors: Q
authors: Wei
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D066264:Datasets as Topic; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D040641:Quantitative Trait Loci; D034741:RNA, Small Interfering / Q000235:genetics*; D012044:Regression Analysis; D015203:Reproducibility of Results; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D015534:Trans-Activators; D004722:Endoribonucleases; C466279:DCP1A protein, human
keywords: Cox regression; PIWI-piRNA pathway; cutaneous melanoma; disease specific survival; single nucleotide polymorphisms