AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking. METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736 sex and age-matched healthy controls recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking. RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A/A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A/A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable/fruit intake on colorectal cancer were much higher for men with GSTT1 present (OR = 0.32, 95%CI = 0.20-0.50) or GSTP1 A/A genotypes (OR = 0.40, 95%CI = 0.25-0.64). These effects remained significant for women. But, the greatest protective effect from vegetable/fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable/fruit intake and GSTT1 present or GSTP1 A/A genotypes with OR=0.17 and 0.21 respectively. CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable/ fruit-related colorectal cancer risk, particularly in men of no smoking history. METHODS: With consents, genotypes of the genes were determined using PCR methods for 727 cases and 736 sex and age-matched healthy controls. AIM: To investigate the colorectal cancer risk associated with polymorphic GSTM1, GSTT1 and GSTP1 and the effect of diet and smoking. recruited at a medical center in the Northern Taiwan. Nurses who were blind to the study hypothesis conducted interviews with study participants for the information of socio-demographic variables, diet and smoking. RESULTS: There was no significant association between GSTM1 genotypes and the disease. Men, not women, with GSTT1 null genotype were at significant risk of colorectal cancer, but limited to rectal tumor, and in men aged 60 years and less. The corresponding association with the GSTP1 with G allele compared to GSTP1 A / A genotype was at borderline significance. Compared to men with GSTT1 present and GSTP1 A / A combined, men with both GSTT1 null and GSTP1 with G allele genotypes were at significant risk (odds r atio (OR) = 1.91, 95% confidence interval (CI) = 1.21-3.02), also limited to the rectal tumor and younger men. The beneficial effects of vegetable / fruit intake on colorectal cancer were much higher for men with GSTT1 present ( OR = 0.32, 95% CI = 0.20-0.50) or GSTP1 A / A genotypes (OR = 0.40, 95% CI = 0.25-0.64). These effects remained significant for women. But, the greatest protective effect from vegetable / fruit intake for women was observed in those with GSTT1 null or GSTP1 with G allele genotypes. In addition, non-smoking men benefitted significantly from combined effect of higher vegetable / fruit intake and GSTT1 present or GSTP1 A / A genotypes with OR = 0.17 and 0.21 CONCLUSION: This study suggests that the GSTT1 gene can modulate the colorectal cancer risk and vegetable / fruit-related colorectal cancer risk, particularly in men of no smoking history.