Quantitative assessment of the association of polymorphisms in the metallothionein 2A gene with cancer risk

Abstract

Objective The aim of the study was to quantitatively assess the association of metallothionein 2A ( MT2A) polymorphisms rs28366003 and rs1610216 with cancer risk. Methods Crude odd ratios (OR) with 95% confidence intervals (CI) were used to estimate associations of the polymorphisms with cancer risk. Results Six eligible case-control studies with 1899 cases and 2437 controls focused on rs28366003, and three of those six studies, with 548 cases and 926 controls, additionally focused on rs1610216. Pooled analysis showed that MT2A rs28366003 and rs1610216 were associated with cancer risk: (AG + GG) vs. AA, OR = 2.67; GG vs. (AG + AA), OR = 5.97; GG vs. AA, OR = 6.80; AG vs. AA, OR = 2.46; G vs. A, OR = 2.67 for rs28366003; and CC vs. (TC+TT), OR = 2.51; CC vs. TT, OR = 2.42 for rs1610216. Subgroup analysis based on ethnicity showed a significant association of rs28366003 with cancer risk in Asian and Caucasian populations. However, a significant association of rs1610216 with cancer risk was found only in the Asian population. Conclusion MT2A rs28366003 and rs1610216 polymorphisms were associated with cancer risk and might serve as genetic biomarkers for predicting cancer risk. However, larger studies are needed to confirm these findings.

An Assessment of MT1A (rs11076161), MT2A (rs28366003) and MT1L (rs10636) Gene Polymorphisms and MT2 Concentration in Women with Endometrial Pathologies

“…SNPs can alter gene expression and influence protein activity; thus, it was suggested that genetic variations of MT isoforms may influence cancer susceptibility [ 49 , 50 , 51 , 52 , 53 , 54 ]. In humans, MTs have four main isoforms (MT1, MT2, MT3 and MT4) and can be further subdivided into functional subisoforms.…”

ptk2 and mt2a Genes Expression in Gastritis and Gastric Cancer Patients with Helicobacter pylori Infection

“…ey showed that MT2A induces apoptosis by stopping the G2/M phase of the cell cycle, and the effect of MT2A on apoptosis is due to the suppression of the NF-KB signaling pathway [9,10]. Wang et al showed that MT2A increases the expression of P21 and BAX proteins by affecting P53 which is a pre-apoptotic protein triggering the cell death process [12]. Previous studies show the positive correlations between mt2a gene polymorphisms and breast, liver, and prostate cancers [11][12][13][14][15].…”

“…Wang et al showed that MT2A increases the expression of P21 and BAX proteins by affecting P53 which is a pre-apoptotic protein triggering the cell death process [12]. Previous studies show the positive correlations between mt2a gene polymorphisms and breast, liver, and prostate cancers [11][12][13][14][15]. In a comparison, the results of the current study showed no statistically significant correlation between mt2a gene ΔCt and patients' demographic characteristics, including clinical manifestations, tumor grade, adenocarcinoma tumor area, age, sex, and H. pylori infection (Table 5).…”

“…As a clinical impact of Mt2a, it has recently been shown that attenuation of MT2A and IkB-α gene expression in human gastric epithelial cells is associated with a poor prognosis in gastric cancer patients [9,10]. Furthermore, some mt2a gene polymorphisms, including rs28366003 and rs1610216, are associated with an increased risk of cancer [11][12][13]. In this regard, some MT-2A gene polymorphisms are associated with adenocarcinoma risk in the Iranian patient population [14].…”