Genomic susceptibility to gastric cancer in Northwest Iran: population-based and case–control studies

Abstract

The age-standardized incidence rate for gastric cancer is estimated to be 11.1% worldwide and 39.1% for Ardabil province in northwest Iran. Single nucleotide polymorphisms (SNPs) occur in coding and non-coding regions, contributing to cancer susceptibility. To identify SNPs predisposing individuals to gastric cancer in this region, we compared 263 variants between the Ardabil population and other populations. Whole exome sequencing was used to determine the distribution of variants in the genomic DNA of 150 volunteers (aged < 35 years) from the general population of Ardabil. We compared allele frequencies with databases such as Iranome, Alfa, GnomAD, and 1000G, and statistically analyzed their correlation with age-standardized incidence rates (ASRs) for gastric cancer in related populations using the Pearson correlation test. Some findings were validated using Sanger-based PCR-Sequencing. We determined the frequency of seventeen variants among 150 individuals with gastric cancer and 150 healthy volunteers (matched for age and sex) as the control group. Nineteen variants, including rs10061133, rs1050631, rs12220909, rs12983273, rs1695, rs2274223, rs2292832, rs2294008, rs2505901, rs2976391, rs33927012, rs3744037, rs3745469, rs4789936, rs4986790, rs4986791, rs6194, rs63750447, and rs6505162, were found to be significantly different between the general population of Ardabil and other populations. Among them, the variants rs1050631, rs12983273, rs1695, rs2274223, rs2292832, rs2505901, rs33927012, rs374569, and rs6505162 showed significant differences between the cases and controls. In this study, 17 variants appeared to be involved in the etiology of the high frequency of gastric cancer in the Ardabil population. Some of the observed differences were consistent with previous case–control and meta-analysis reports from various parts of the world. These findings motivate further cohort investigations in this population. Ultimately, identifying prognostic factors can help diagnose individuals predisposed to gastric cancer in this population.