Abstract
It has been suggested that the genetic variation in human chromosome 6p21.1 has potential importance for the susceptibility to gastric cancer (GC). The study aims to explore the relationship between the long non-coding RNA (lncRNA) polymorphisms in 6p21.1 and the risk of GC as well as atrophic gastritis (AG). Genotyping for eight single nucleotide polymorphisms (SNPs) was conducted using Sequenom MassARRAY platform in a total of 2507 northern Chinese subjects, including 749 GC cases, 878 AG cases and 880 controls. The results showed rs61516247 was associated with an increased AG risk in overall population (AA vs. GG: P = 0.046, OR = 1.46; A vs. G: P = 0.037, OR = 1.18). Four SNPs, rs61516247, rs1886753, rs7747696 and rs7749023 were associated with AG risk in some specific subgroups. Among them, rs1886753 had an interaction effect with H.pylori infection on AG risk (Pinteraction = 0.038, OR = 1.62). In prognosis analysis, two SNPs, rs80112640 (AG+GG vs. AA: P = 0.047, HR = 0.56; G vs. A: P = 0.039, HR = 0.57) and rs72855279 (P = 0.043, HR = 0.57) were found to improve the overall survival of GC patients. In conclusion, lncRNA SNPs in 6p21.1 are associated with AG risk and GC prognosis. Our study provides all-new research clues for screening lncRNA-based biomarkers in the cancer-related hotspot region 6p21.1 with the potential to predict risk and prognosis of GC along with its precursor.
Highlights
Genetic variation is a common phenomenon in the species evolution
This case-control study explored the relationship of seven long non-coding RNA (lncRNA) single nucleotide polymorphisms (SNPs) in 6p21.1 with the risk and prognosis for gastric cancer (GC) and atrophic gastritis (AG) in a total of 2507 subjects
We newly found the rs61516247 polymorphism was associated with an increased AG risk in overall population
Summary
Genetic variation is a common phenomenon in the species evolution. As the most common form of genetic variation, the single nucleotide polymorphism (SNP) has been extensively investigated in the relationship with various diseases. All the present studies focused on this hotspot region were related to protein-coding genes but few for non-coding RNAs (ncRNAs), with well-known significant gene regulative function. SNPs in six lncRNA genes have been reported to be associated with GC risk and prognosis, including H19, HOTAIR, TINCR, PRNCR1, NR_024015 and CASC8 [10,11,12,13,14]. It is remain unclear whether the lncRNA SNPs located in 6p21.1, the cancerrelated hotspot region, are related to GC as well as its precancerous diseases
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