Abstract
BackgroundPublished data on the association between genetic variants on the 8q24 chromosome and gastric cancer (GC) susceptibility are inconclusive. Here we present a meta-analysis designed to evaluate the relationship between 8q24 variants (single nucleotide polymorphisms (SNPs) labeled rs6983267 and rs1447295) and risk of developing GC.MethodsA literature search was performed using studies published on PubMed, Science Direct, OVID and Web of Science databases up to December 2016. Studies were selected based on our enrollment criteria, relevant data was extracted from each study and the odds ratios (OR), and 95% confidence intervals (CI) were calculated and used to assess the strength of associations found between 8q24 polymorphisms and GC risk. Conclusions about acceptable strong associations were made after taking into account sample heterogeneity and sensitivity analyses.ResultsA total of seven studies containing ten case-control studies were selected. Among these studies were six studies of 1,421 GC patients and 3,393 controls examining the role of the rs6983267 SNP and four studies including 779 cases and 1,266 controls examining rs1447295 SNP. The pooled results of these studies indicated that there was no significant association between both genetic variants and GC susceptibility using an allele, dominant, recessive and homozygote genetic models. When using a heterozygote genetic model, a significant increase was found in the association of GC risk for rs6983267 SNP (OR = 1.07, 95% CI = 1.01–1.12, P = 0.015), whereas for rs1447295 SNP a significant decreased risk was detected (OR = 0.82, 95% CI = 0.69–0.98, P = 0.030). In subgroup analyses based on ethnicity and genotyping methods, similar non-significant results were observed for the rs1447295 variant using the four genetic models (allele, dominant, recessive or homozygote models) and for the rs6983267 variant using only the allele, recessive and homozygote models. However, after a multiple testing correction to our calculations, these associations remained non-significant.ConclusionMeta-analysis of gastrointestinal cancer genetic analysis studies did not confirm an association between 8q24 chromosome polymorphisms (specifically rs6983267 and rs1447295) and susceptibility to GC in the general populations.
Highlights
Gastric cancer (GC), the fifth most common cancer worldwide, is rampant in many countries around the world, causing more than 841,000 deaths each year [1]
Studies were selected based on our enrollment criteria, relevant data was extracted from each study and the odds ratios (OR), and 95% confidence intervals (CI) were calculated and used to assess the strength of associations found between 8q24 polymorphisms and GC risk
When using a heterozygote genetic model, a significant increase was found in the association of GC risk for rs6983267 single nucleotide polymorphism (SNP) (OR = 1.07, 95% CI = 1.01–1.12, P = 0.015), whereas for rs1447295 SNP a significant decreased risk was detected (OR = 0.82, 95% CI = 0.69–0.98, P = 0.030)
Summary
Gastric cancer (GC), the fifth most common cancer worldwide, is rampant in many countries around the world, causing more than 841,000 deaths each year [1]. It has been shown that among people who are exposed to the same environmental carcinogenic factors, only a fraction develop GC This finding suggests that there are discrepancies in the genetic background of susceptible people which may lead to individual differences in GC susceptibility [6, 7]. Within the 8q24 locus lies a 1.18 Mb region that contains unknown genes Downstream of this so called “gene desert” are two candidate cancer susceptibility genes, the OCT4 pseudogenes POU5F1P1 and c-MYC. Over the last two decades, a number of molecular epidemiological studies have investigated the link between two polymorphisms, rs6983267 and rs1447295, in this region and analysis of association to GC susceptibility have revealed inconsistent results. Taking into account all of these controversial results, we executed the first meta-analysis study to evaluate the existence of any association between polymorphism variants on the 8q24 chromosome ( rs6983267 and rs1447295) and GC susceptibility
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