Association between the SNPs in trace element-related metabolic genes and the risk of gastric cancer: a case–control study in Xianyou of China

Abstract

This study aims to analyse the potential relationship between single-nucleotide polymorphism (SNPs) in trace elementrelated metabolic genes GSTM3, GSTP1, GPX1 and NKG2D and the risk of gastric cancer. A case-control study was conducted in the hospital of Xianyou, Fujian, China. In this study, a total of 299 patients with histopathological diagnosis in gastric cancer and 295 healthy control subjects were involved. Association between the SNPs in trace element-related metabolic genes and gastric cancer risk was analysed using the unconditional logistic regression model. No relationship was found between the SNPs of GSTM3 and GPX1 genes and gastric cancer risk. However, the risk of gastric cancer is related to the SNPs of NKG2D gene (rs1049174). Patients who carry the rs1049174 GG genotype have a higher incidence of the gastric cancer and a multivariate odds ratio (OR) of 1.85 (95% confidence intervals (CI): 1.02-3.38). Through haplotype analysis, two haplotypes (i.e. A_rs1746123-T_rs10431294-G_rs1049174 and T_rs1746123-T_rs10431294-C_rs1049174), OR of 0.29 (95% CI: 0.15-0.56) and 0.33, (95% CI: 0.22-0.50), respectively, were found to have lower incidence of gastric cancer. Meanwhile, another two haplotypes (T_rs1746123-C_rs10431294-C_rs1049174 and T_rs1746123-T_rs10431294-G_rs1049174), OR of 1.81 (95% CI: 1.40-2.34) and 3.09 (95% CI: 2.30-4.16), respectively, were found to have a higher incidence of gastric cancer. Further, no influence of the haplotype on the risk of cardia gastric cancer was found. However, the haplotype T_rs1746123-T_rs10431294-C_rs1049174 had lower incidence of noncardia gastric cancer by 46%. Our data showed that polymorphisms of trace element-related metabolic genes are important in gastric cancer pathology.

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

“…Haplotypes associated with increasing/decreasing recurrent miscarriage risk among North African women [81] (ATG, TTC) > (TTC, TTG) (rs1746123, rs10431294, rs1049174) KLRK1 haplotypes associated with decreasing/increasing gastric cancer risk in Chinese patients [61] To the best of our knowledge, among all of the genetic substitutions located within the KLRK1 gene, two of them have been uncovered as functional polymorphisms: rs1049174 and rs2255336. The first of them, rs1049174 (C > G), is a synonymous substitution positioned in the 3 untranslated region (UTR) of KLRK1 gene, within the binding site of the negatively regulating microRNA-1245 [90].…”

“…The HNK1 haplotype (represented by the rs1049174 G allele) was found to reduce the risk of specific cancers in studies on colorectal (colon, rectum, or both) [57], aerodigestive tract (head, neck and esophageal) [59], and breast cancers [60]. One inconsistent finding indicated that GG and GC genotypes of rs1049174 are related to gastric cancer incidence [61], although it can be assumed that rs1049174 G allele has a protective effect on cancer occurrence in different populations. Another genetic variant, rs11053781 A, from the intron of KLRK1 and rs2617167 G allele located in the intergenic KLRC4-KLRK1 region, is a non-risk alleles in the development of cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC) [85].…”