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<p>Bladder Cancer is becoming increasingly prevalent in Iraq and it represents a significant public health challenge. Glutathione S-transferases (GSTs)—an enzyme of phase II detoxification provides defense for oxidative stress and various carcinogens. The current study investigated the association of bladder cancer risk among Iraqi patients with different studied variants in GST genes GSTM1, GSTT1, and GSTP1. This case-control study comprised 238 histologically confirmed bladder cancer patients and 310 age- and sex-matched healthy controls. Genotyping for GSTM1, GSTT1, and GSTP1 was carried out using tetra-primer ARMS-PCR. Biochemical parameters like oxidative stress markers (MDA, GSH, and TAC) were assessed. Logistic regression, adjusted for relevant confounders, was used to assess the associations. A higher incidence of bladder cancer was substantially linked to the GSTM1 null (53.8% vs. 32.9%, OR = 2.34, <i>p</i> &lt; 0.001), GSTT1 null (40.8% vs. 27.4%, OR = 1.87, <i>p</i> = 0.001), and GSTP1 Val/Val (18.5% vs. 9.7%, OR = 2.13, <i>p</i> = 0.004) genotypes. The risk increased with the number of risk genotypes, consistent with a dose-response relationship (OR = 4.76 with all three risk genotypes, <i>p</i> &lt; 0.001). Smokers and individuals aged over 60 displayed stronger associations. Increased levels of MDA and decreased levels of GSH were observed in patients with risk genotypes, indicating higher oxidative stress. In the Iraqi population, the presence of genetic polymorphisms in GSTM1, GSTT1, and GSTP1 significantly heightens susceptibility to bladder cancer, particularly in conjunction with other environmental risk factors. These parameters of altered oxidative stress suggesting diminished detoxification capacity may enhance cancer risk, support the possibility of employing these polymorphisms for more precise screening and preventive strategies.</p>

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Association of Genetic Polymorphisms of Glutathione S-Transferase (GSTM1, GSTT1, GSTP1) with Bladder Cancer Susceptibility in Iraqi Patients: A Case-Control Study

  • 期刊论文

  • 发表日期：

    2025年7月24日

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  • Wisam Hindawi Hoidy,
  • Ahmed Ghdhban Al-Ziaydi,
  • Mohammed Ouda Orabiy

摘要

Bladder Cancer is becoming increasingly prevalent in Iraq and it represents a significant public health challenge. Glutathione S-transferases (GSTs)—an enzyme of phase II detoxification provides defense for oxidative stress and various carcinogens. The current study investigated the association of bladder cancer risk among Iraqi patients with different studied variants in GST genes GSTM1, GSTT1, and GSTP1. This case-control study comprised 238 histologically confirmed bladder cancer patients and 310 age- and sex-matched healthy controls. Genotyping for GSTM1, GSTT1, and GSTP1 was carried out using tetra-primer ARMS-PCR. Biochemical parameters like oxidative stress markers (MDA, GSH, and TAC) were assessed. Logistic regression, adjusted for relevant confounders, was used to assess the associations. A higher incidence of bladder cancer was substantially linked to the GSTM1 null (53.8% vs. 32.9%, OR = 2.34, p < 0.001), GSTT1 null (40.8% vs. 27.4%, OR = 1.87, p = 0.001), and GSTP1 Val/Val (18.5% vs. 9.7%, OR = 2.13, p = 0.004) genotypes. The risk increased with the number of risk genotypes, consistent with a dose-response relationship (OR = 4.76 with all three risk genotypes, p < 0.001). Smokers and individuals aged over 60 displayed stronger associations. Increased levels of MDA and decreased levels of GSH were observed in patients with risk genotypes, indicating higher oxidative stress. In the Iraqi population, the presence of genetic polymorphisms in GSTM1, GSTT1, and GSTP1 significantly heightens susceptibility to bladder cancer, particularly in conjunction with other environmental risk factors. These parameters of altered oxidative stress suggesting diminished detoxification capacity may enhance cancer risk, support the possibility of employing these polymorphisms for more precise screening and preventive strategies.