Glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of noxious agents. Genes encoding for GSTA1, GSTP1, GSTT1, and GSTM1 proteins are polymorphic in humans, which can result in (partial) loss of enzyme activity. Previous epidemiologic studies have associated dysfunction of these GST genes with a higher risk of cancer, but this is still controversial. The aim of this study was to investigate the susceptibility to gastric cancer in relation to the above-mentioned GST polymorphisms. Patients visiting the Can Tho General Hospital in Vietnam between January 2004 and August 2004 for upper gastrointestinal endoscopy, who were diagnosed with gastric cancer, were compared with a control group of endoscoped dyspepsia patients with no history of malignancy. Genotypes of the GSTs mentioned above were assessed by multiplex PCR. Fifty-nine patients with gastric cancer (mean age: 63 years, 80% males), and 109 dyspeptic controls (mean age: 46 years, 69% males) were included in this study. The frequencies of the combined heterozygote and homozygote mutant GSTA1 and GSTP1 genotypes were 10% and 48% in patients with gastric cancer versus 28% and 40% in dyspeptic controls, respectively. GSTT1 and GSTM1 were deleted in 42% and 73% of patients with gastric cancer and in 35% and 69% of the controls, respectively. The GSTA1 homozygous wild-type genotype was significantly more often present in patients with gastric cancer compared with controls (odds ratio 4.3, 95% CI 1.2-17), which was even more apparent after adjustment for age, gender, current smoking, current alcohol consumption, and polymorphisms in GSTP1, GSTT1, or GSTM1 (odds ratio 5.0, 95% CI 1.2-25). The present work shows that the homozygous wild-type GSTA1 genotype is associated with gastric cancer in a Vietnamese population, whereas there was no relationship with polymorphisms in GSTP1, GSTT1, or GSTM1.