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A genetic variation in the CpG island of pseudogene GBAP1 promoter is associated with gastric cancer susceptibility
Author(s) -
Ma Gaoxiang,
Liu Hanting,
Du Mulong,
Zhang Gang,
Lin Yadi,
Ge Yuqiu,
Wang Meilin,
Jin Guangfu,
Zhao Qinghong,
Chu Haiyan,
Gong Weida,
Zhang Zhengdong
Publication year - 2019
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32081
Subject(s) - single nucleotide polymorphism , genetics , pseudogene , biology , genome wide association study , genotype , genetic association , cpg site , promoter , dna methylation , snp , gene , haplotype , genome , gene expression
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 .