A genetic variation in the CpG island of pseudogene GBAP1 promoter is associated with gastric cancer susceptibility.
Cancer
; 125(14): 2465-2473, 2019 07 15.
Article
en En
| MEDLINE
| ID: mdl-30951202
ABSTRACT
BACKGROUND:
Previous genome-wide association studies (GWASs) have identified that several single nucleotide polymorphisms (SNPs) are implicated in gastric cancer (GC) risk. However, the multiple statistical comparisons of GWASs may reject some true biological positives with subthreshold P values.METHODS:
This study annotated the genomic locations of all CpG islands in the genome using the Encyclopedia of DNA Elements (ENCODE). The SNPs in the regions were then genotyped using the Illumina 660W Quad chip. The effects of the prominent variations on GC risk were further confirmed in the other independent cohorts.RESULTS:
SNP rs2990245, which is located in the promoter of pseudogene GBAP1, was associated with GC risk using GWASs data. An additional cohort of 1275 GC patients and 1424 controls validated that individuals with the CC genotype had a 62% decreased risk of GC compared with those who carried the TT genotype (P = 2.01E-04) in the codominant model. The significant association was observed in the additive, dominant, and recessive models. A meta-analysis combining the results from the GWASs and replication studies revealed that rs2990245 was significantly associated with decreased GC risk (P = 5.59E-12). Importantly, rs2990245 can regulate the expression of GBAP1 by influencing the methylation status of the GBAP1 promoter. GBAP1 can act as a competing endogenous RNA by binding competitively with micro-RNA-212-3p and then promoting GBA expression.CONCLUSION:
rs2990245 is significantly associated with a decreased risk of GC. Pseudogene GBAP1 contributes to the development and progression of GC by sequestering the miR-212-3p from binding to GBA.Palabras clave
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Seudogenes
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Regiones Promotoras Genéticas
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Islas de CpG
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Glucosilceramidasa
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer
Año:
2019
Tipo del documento:
Article
País de afiliación:
China