There have been few studies of the associations of genetic polymorphisms with precancerous gastric lesions. We conducted a cross-sectional study to compare the prevalences of several genetic polymorphisms in 302 subjects with mild chronic atrophic gastritis with prevalences in 606 subjects with deep intestinal metaplasia or dysplasia. This stratified random sample of 908 subjects was selected and analyzed for genetic polymorphisms from 2,628 individuals who had gastric biopsies with histopathology in 1989 in Linqu County, Shandong Province, China. In subjects with mild chronic atrophic gastritis, the frequencies of the variant (less common) alleles of CYP2E1 RsaI, CYP2E1 DraI, GSTP1, ALDH2, and ODC were, respectively, 0.156, 0.201, 0.189, 0.190, and 0.428. The frequencies of the null genotypes of GSTM1 and GSTT1 in the mild chronic atrophic gastritis group were 0.509 and 0.565, respectively. Comparing mild chronic atrophic gastritis with deep intestinal metaplasia or any degree of dysplasia, we found no statistically significant associations with any genotype from these loci for dominant, additive, or recessive inheritance models. There was no statistically significant evidence of multiplicative interactions between any pair of genotypes based on CYP2E1 RsaI, CYP2E1 DraI, GSTP1, GSTM1, or GSTT1; nor between Helicobacter pylori status and any of these five loci; nor between smoking status and GSTP1, GSTM1, or GSTT1; nor between alcohol consumption and ALDH2. Statistically significant interactions were noted between salt consumption and GSTP1 and between sour pancake consumption and CYP2E1 RsaI. There was, moreover, a statistically significant interaction (odds ratio, 1.78; 95% confidence interval, 1.03-3.08) between CYP2E1 DraI and smoking at least one cigarette per day. A positive but not statistically significant interaction was also seen between CYP2E1 RsaI and smoking status. These polymorphisms do not seem to govern progression from mild chronic atrophic gastritis to advanced precancerous gastric lesions, but the effects of smoking may be accentuated in individuals carrying variants of CYP2E1.