SNP interactions of PGC with its neighbor lncRNAs enhance the susceptibility to gastric cancer/atrophic gastritis and influence the expression of involved molecules

Abstract

Multidimensional interactions of multiple factors are more important in promoting cancer initiation. Gene‐gene interactions between protein‐coding genes have been paid great attention, while rare studies refer to the interactions between encoding and noncoding genes. Our research group previously found encoding gene PGC polymorphisms could affect the susceptibility to atrophic gastritis (AG) and gastric cancer (GC). Interestingly, several SNPs in long noncoding RNA (lncRNA) genes, just adjacent to PGC, were found to be associated with AG risk and GC prognosis afterward. This study aims to explore the SNP interactions between PGC and its neighbor lncRNAs on the risk of AG and GC. Genotyping for seven PGC SNPs and seven lncRNA SNPs was conducted using Sequenom MassARRAY platform in a total of 2228 northern Chinese subjects, including 536 GC cases, 810 AG cases, and 882 controls. We found 15 pairwise PGC‐lncRNAs SNPs had interactions: Five pairs were associated with AG risk, and ten pairs were associated with GC risk. Moreover, two GC‐related interactions PGC rs6939861 with lnc‐C6orf‐132‐1 rs7749023 and rs7747696 survived the Bonferroni correction (P correction = 0.049 and 0.007, respectively). Several combinations showed obvious epistasis and cumulative effects on disease risk. Some three‐way interactions of SNPs with smoking and drinking could also be observed. Besides, a few interacting SNPs showed correlations with the expression levels of PGC protein and related lncRNAs in serum. Our study would provide research clues for further screening combination biomarkers uniting both protein‐coding and noncoding genes with the potential in prediction of the susceptibility to GC and its precursor.

Transcriptome Analysis of lncRNA–mRNA Interactions in Chronic Atrophic Gastritis

“…It also has been reported that lncRNAs play an important role in the pathogenesis of GC ( Lin et al, 2014 ). According to studies on lncRNAs in GC and CAG, there is one report showing that single-nucleotide polymorphisms (SNPs) interact with PGC, a coding gene with its adjacent lncRNAs, which could affect a person’s susceptibility to GC and CAG ( Lv et al, 2018 ). In that study, 15 pairwise interacting PGC-lncRNA SNPs were found, in which five pairs were relevant to CAG risk.…”

Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer

“…Therefore, rs3807598, rs2067087, and rs17427960 polymorphisms may also be applied to predict CRC susceptibility in some specific populations, such as young people and individuals without smoking or drinking history. Furthermore, the role of one single factor on disease risk was limited and usually reported to be weak, but the combination of multiple factors may have stronger roles and markedly affect the susceptibility to cancer [40,41]. To identify some potential combination effects that cannot be revealed in univariate analyses, we evaluated the interactions between all the environmental factors and SNP genotypes, although only H. pylori infection was demonstrated to be associated with CRC risk.…”

Identification of PGC-related ncRNAs and their relationship with the clinicopathological features of Gastric Cancer

“…Liu et al found that the serum expression level of lncRNAs adjacent to PGC could distinguish gastric cancer, atrophic gastritis and superficial gastritis [16]. In addition, Lv et al reported that 10 pairwise PGC-lncRNA single nucleotide polymorphisms (SNPs) were associated with gastric cancer risk, and might enhance the susceptibility to gastric cancer [17]. Several other studies focused on the miRNAs targeting PGC and their relationship with gastric cancer.…”