Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies

Abstract

Objective In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms (SNPs) on candidate genes and gastric cancer (GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC. Methods We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability (FPRP) test. Results Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1 (rs1760944), DNMT1 (rs16999593), ERCC5 (rs751402), GSTT1 (null/presence), MDM2 (rs2278744), PPARG (rs1801282), TLR4 (rs4986790), IL-17F (rs763780), and CASP8 (rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies. Conclusions Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk; however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.

The Associations of Dietary Iron Intake and the Transferrin Receptor (TFRC) rs9846149 Polymorphism with the Risk of Gastric Cancer: A Case–Control Study Conducted in Korea

“…An insufficient sample size of intestinal type may be responsible for the nonsignificant association between TFRC and GC in this study. Additionally, TFRC rs9846149 has not been investigated in relation to GC risk [ 17 ], and only 5% of participants were GG homozygous. Thus, further studies with a larger sample size are necessary to evaluate this association.…”

“…In an environment without free iron, H. pylori will acquire iron from proteins, and TFRC will be used as an element for attachment and pathogenesis [ 15 ]. Single nucleotide polymorphisms (SNPs), which are the most common type of genetic mutation, may influence susceptibility to GC [ 17 ]. The effects of exposure to environmental factors may be modulated by genetic variants through the regulation of multiple biological pathways during gastric carcinogenesis [ 18 ].…”

NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori

“…According to the IARC, H. pylori is considered as carcinogenic to humans (Group 1). A systematic review and meta-analysis [ 5 ] of published studies assessing the association of genetic factors with gastric cancer, described nine polymorphisms with significant association. Many of them were found using a candidate gene approach.…”

“…Some studies assessing the role of polymorphisms in TLR2 , TLR4 , TLR5 , NOD1 and NOD2 in gastric cancer have been published. The associations of TLR4 rs4986790 (Asp299Gly) (minor allele frequency-MAF = 0.06) and rs4986791 (MAF = 0.04) were found to be statistically significant in meta-analyses [ 5 ]. The evidence for association of polymorphisms in TLR5 [ 17 ], NOD1 and NOD2 is scarce [ 18 , 19 ].…”

Cytokine TGF-β1, TNF-α, IFN-γ and IL‐6 Gene Polymorphisms and Localization of Premalignant Gastric Lesions in Immunohistochemically H. pylori-negative Patients

“…Recent meta-analysis support that single nucleotide polymorphisms may be used for the assessment of genetic predisposition to gastric cancer, with ethnicity, environmental factor and cancer subtype contributing to inconsistency in the results 5 . From among all molecular factors playing a role in progression from inflammation toward preneoplastic gastric lesions and cancer, recent research has focused on the possible influence of different type cytokine gene variants 6 . Recently, it was shown that cytokine gene variants are associated with susceptibility to different types of malignancy in a Romanian population 7 .…”