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

• Published in: Cancer medicine (Malden, MA) Vol. 7; no. 10; pp. 5252 - 5271
• Main Authors: Lv, Zhi, Sun, Liping, Xu, Qian, Gong, Yuehua, Jing, Jingjing, Dong, Nannan, Xing, Chengzhong, Yuan, Yuan
• Format: Journal Article
• Language: English
• Published: Bognor Regis John Wiley & Sons, Inc 01.10.2018
• Subjects: Epistasis; Gastric cancer; Gastritis; Genes; Genotyping; Proteins; Ribonucleic acid; RNA; Single-nucleotide polymorphism; Smoking; Beijing China; China
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1743

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 SNP s in long noncoding RNA (lnc RNA ) 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 lnc RNA s on the risk of AG and GC . Genotyping for seven PGC SNP s and seven lnc RNA SNP s was conducted using Sequenom Mass ARRAY platform in a total of 2228 northern Chinese subjects, including 536 GC cases, 810 AG cases, and 882 controls. We found 15 pairwise PGC ‐lnc RNA s SNP s 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 SNP s with smoking and drinking could also be observed. Besides, a few interacting SNP s showed correlations with the expression levels of PGC protein and related lnc RNA s 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.