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<p>Gastric cancer (GC) represents a major health burden in South Asia and Iran, with genetic susceptibility varying substantially across populations. We conducted a systematic meta-analysis of gene-based association studies to identify genetic risk factors for gastric cancer in South Asia and Iran, following PRISMA guidelines. PubMed and Google Scholar were searched for eligible studies. Heterogeneity was assessed using Cochran’s Q-test; meta-analyses employed fixed-effect and random-effects models with Benjamini–Hochberg false discovery rate (FDR) correction. We evaluated publication bias using Begg’s Funnel plots and Egger’s test for variants appearing in ≥ 10 studies. Subgroup analyses stratified by <i>Helicobacter pylori</i> infection status and sex; meta-regression assessed effect modification. Analysis of 48 studies (5396 cases; 8330 controls) identified 27 variants across 21 genes, of which 13 showed nominal associations (<i>p</i> &lt; 0.05) and four remained significant after FDR correction (p<sub>FDR</sub> &lt; 0.05). The rs2279744/<i>MDM2</i> variant showed the most robust association, conferring consistently elevated GC risk across additive, dominant, and recessive inheritance models without evidence of publication bias. <i>IL-1β</i> polymorphisms (rs16944, rs1143627) were associated with risk specifically in <i>H. pylori</i>-positive patients, whereas rs2234663/<i>IL-1RN</i> was associated with <i>H. pylori</i>-negative cases. Four pharmacogenomic variants predicted chemotherapy outcomes, including rs1695/<i>GSTP1</i> (oxaliplatin neuropathy), rs1799964/<i>TNF</i> (thrombocytopenia risk), rs1042522/<i>TP53</i> (reduced cisplatin–paclitaxel efficacy), and rs13181/ERCC2 (improved response and survival). These findings identify population-specific genetic determinants of GC susceptibility and treatment response, supporting targeted prevention and personalized therapeutic strategies in South Asian populations. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.</p>

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Genetic predisposition to gastric cancer and treatment outcomes in South Asian and Iranian populations: a comprehensive meta-analysis

  • 期刊论文

  • 发表日期：

    2026年6月25日

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  • Souradeep Banerjee,
  • Bratati Dutta,
  • Soumili Biswas,
  • Sutanuka Sengupta,
  • Samsiddhi Bhattacharjee,
  • Debmalya Sengupta,
  • Mainak Sengupta

摘要

Gastric cancer (GC) represents a major health burden in South Asia and Iran, with genetic susceptibility varying substantially across populations. We conducted a systematic meta-analysis of gene-based association studies to identify genetic risk factors for gastric cancer in South Asia and Iran, following PRISMA guidelines. PubMed and Google Scholar were searched for eligible studies. Heterogeneity was assessed using Cochran’s Q-test; meta-analyses employed fixed-effect and random-effects models with Benjamini–Hochberg false discovery rate (FDR) correction. We evaluated publication bias using Begg’s Funnel plots and Egger’s test for variants appearing in ≥ 10 studies. Subgroup analyses stratified by Helicobacter pylori infection status and sex; meta-regression assessed effect modification. Analysis of 48 studies (5396 cases; 8330 controls) identified 27 variants across 21 genes, of which 13 showed nominal associations (p < 0.05) and four remained significant after FDR correction (pFDR < 0.05). The rs2279744/MDM2 variant showed the most robust association, conferring consistently elevated GC risk across additive, dominant, and recessive inheritance models without evidence of publication bias. IL-1β polymorphisms (rs16944, rs1143627) were associated with risk specifically in H. pylori-positive patients, whereas rs2234663/IL-1RN was associated with H. pylori-negative cases. Four pharmacogenomic variants predicted chemotherapy outcomes, including rs1695/GSTP1 (oxaliplatin neuropathy), rs1799964/TNF (thrombocytopenia risk), rs1042522/TP53 (reduced cisplatin–paclitaxel efficacy), and rs13181/ERCC2 (improved response and survival). These findings identify population-specific genetic determinants of GC susceptibility and treatment response, supporting targeted prevention and personalized therapeutic strategies in South Asian populations. This article aligns with SDG 3 (Good Health and Well-Being) of the UN Agenda for Sustainable Development.