Journal Article

Glutathione-<i>S</i>-transferase gene polymorphisms in colorectal cancer patients: interaction between <i>GSTM1</i> and <i>GSTM3</i> allele variants as a risk-modulating factor

Alexandre Loktionov, Mark A. Watson, Marc Gunter, William S.L. Stebbings, Chris T.M. Speakman and Sheila A. Bingham

in Carcinogenesis

Volume 22, issue 7, pages 1053-1060
Published in print July 2001 | ISSN: 0143-3334
Published online July 2001 | e-ISSN: 1460-2180 | DOI:
Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor

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The distribution of polymorphisms in the glutathione S-transferase (GST) family genes has been studied in 355 healthy controls and 206 cancer (59 proximal and 147 distal) patients. All controls were subjected to flexible sigmoidoscopy. Odds ratios (OR) after stratification by age, gender and smoking were slightly higher in the cancer group as a whole for GSTM1-null (*0/*0), GSTT1-null (*0/*0) and GSTM3 *A/*B or *B/*B when compared with the control group, but the differences did not reach statistical significance. GSTP1 variants had no effect. Separate analysis of patients with proximal and distal tumours has shown stronger associations for the distal cancers, the GSTM3*B allele presence being significantly more frequent in these patients [OR = 1.77; 95% confidence interval (CI) = 1.15–2.74]. Taking into account strong linkage between the GSTM1*A and GSTM3*B alleles, a separate analysis of the GSTM1-nulled individuals was undertaken. The combination of GSTM1-null genotype with GSTM3*B allele presence (*A/*B or *B/*B) was significantly overrepresented among patients with proximal and distal tumours taken together (OR = 2.12; 95% CI = 1.24–3.63), and especially in distal cancer patients (OR = 2.75; 95% CI = 1.56–4.84). Male individuals displayed a stronger association between the presence of the GSTM1-null in combination with GSTM3 *A/*B or *B/*B and distal tumours with a higher odds ratio (OR = 3.57; 95% CI = 1.73–7.36). In contrast, the frequency of GSTM1 *B/*0 or *B/*B combined with GSTM3 *A/*A was significantly lower in patients with distal colorectal cancer, especially in males (OR = 0.37; 95% CI = 0.15–0.92). Neither of these combinations was associated with proximal tumours. Our findings suggest that interactions of polymorphic genotypes within the GSTM gene cluster affect individual susceptibility to colorectal carcinogenesis, the GSTM3*B variant presence being a risk factor especially in combination with the GSTM1-null genotype.

Keywords: CI, confidence interval; OR, odds ratio; PAH, polycyclic aromatic hydrocarbons; YY1, Yin Yang 1; GST, glutathione S-transferase.

Journal Article.  5877 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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