Long non-coding RNA polymorphisms in 6p21.1 are associated with atrophic gastritis risk and gastric cancer prognosis

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 (P_interaction = 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.