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Genetic polymorphisms of glutathione S-transferase genes GSTP1, GSTM1, and GSTT1 and risk of esophageal and gastric cardia cancers

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Abstract

Glutathione S-transferase (GST) enzymes are known to metabolize tobacco-related carcinogens. Previous studies on the association of functional polymorphisms of GST genes with esophageal squamous cell carcinoma have yielded conflicting but overall null results. A few studies of esophageal adenocarcinoma were likewise conflicting, but the scarcity of data is striking. We aimed to study associations of the GSTM1 and GSTT1 null deletion polymorphisms as well as the GSTP1 Ile105Val polymorphism with risks for esophageal and gastric cardia cancers. DNA was prepared from 96 and 79 cases of esophageal adenocarcinoma and squamous cell carcinoma, respectively, 126 cardia cancer cases, and 471 population-based controls. Pyrosequencing typed the GSTP1 Ile105Val polymorphism, while multiplex PCR detected GSTM1 and GSTT1 deletions. Logistic regression modeling estimated odds ratios (ORs) with 95% confidence intervals (CIs). None of the studied polymorphisms were related to the risk of esophageal adenocarcinoma, but the variant GSTP1 Val105 allele was associated with an increased risk of esophageal squamous cell carcinoma (OR = 1.7; 95% CI 1.0–2.9) and tended to be weakly, positively linked to cardia cancer (OR = 1.4; 95% CI 0.9–2.1). Finally, we performed a meta-analysis and found that GSTP1 polymorphism seems to be associated with the risk of esophageal squamous cell carcinoma among Caucasian population (OR = 1.4; 95% CI 1.0–2.2; p value for heterogeneity test 0.34).

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Acknowledgments

We are in debt to Dr. Bo Ding for genotyping of GSTP1 gene. This study supported by a grant from Karolinska Institutet. Original case–control study (SECC study) was supported by a grant from the National Institute of Health (R01 CA57947-03) and two grants (4559-B01-01XAA, 4758-B02-01XAB) from the Swedish Cancer Society.

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Authors and Affiliations

  1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77, Stockholm, Sweden

    Kazem Zendehdel, Olof Nyren & Weimin Ye

  2. Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

    Kazem Zendehdel

  3. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden

    Shahram Bahmanyar

  4. Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran

    Shahram Bahmanyar

  5. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden

    Shane McCarthy & Bjorn Andersson

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  1. Kazem Zendehdel
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  2. Shahram Bahmanyar
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Correspondence to Kazem Zendehdel.

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Zendehdel, K., Bahmanyar, S., McCarthy, S. et al. Genetic polymorphisms of glutathione S-transferase genes GSTP1, GSTM1, and GSTT1 and risk of esophageal and gastric cardia cancers. Cancer Causes Control 20, 2031–2038 (2009). https://doi.org/10.1007/s10552-009-9399-7

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  • DOI: https://doi.org/10.1007/s10552-009-9399-7

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