These results imply that the GSTM1 null genotype has a weak correlation, but another 4 genetic polymorphisms are unlikely to be associated, with oral cavity cancer among Japanese.
These results suggest that the GSTM1 null and GSTM3 intron 6 polymorphisms play an important role in risk for oral cancer among African-Americans and implicates the mu class of GSTs as important tobacco carcinogen detoxifying enzymes in this population.
An association of oral squamous cell carcinoma (SCC) susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene and GSTM1 polymorphism were reported in our previous study (Sato M, Sato T, Izumo T, Amagasa T. Genetic polymorphism of drug-metabolizing enzymes and susceptiblility to oral cancer.Carcinogenesis 1999;20:1927-31).
Among the null GSTM1 individuals, those who smoke, consume alcohol, and/or chew betel quid have a significantly increased risk for oral cancer with an odd ratio (OR) = 4.0 (95% CI = 1.2-13.7), OR = 7.2 (95% CI = 1.5-33.8), and OR = 4.4 (95% CI = 1.1-17.8), respectively.
The null variant of GSTM1 was associated with a marginally significant decrease in oral cancer risk [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.3-1.0, and P for trend = 0.09].
The prevalence of GSTM1 deficiency (null) was significantly higher for patients with oral cancer of the floor of the mouth (OR=3.67, 95% CI=1.11-12.11, P<0.05).
The prevalence of the GSTM1 null genotypes was 29/87 (33.3%) and 21/40 (52.5%) in controls and oral cancer cases, respectively but the differences were not significant (OR=2.2; 95%CI=0.96-5.1; p=0.06).
GSTM1 null alone or associated with CYP1A1 increased the risk of head and neck cancer; the CYP2E1PstI mutated allele increased the risk for only oral cancer.
A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3).
Differences in the GSTM1 and GSTT1 null genotype frequencies were observed between individuals of European origin and African origin, but these genotypes do not seem to influence the risk of oral cancer.
The data suggest that variant genotypes of CYP1A1 might not be risk factors for oral cancer, whereas GSTM1 null genotype significantly increases susceptibility to oral cancer in Asians but not Caucasians.
The aim of this study was to estimate the relationship of glutathione S-transferases (GST)P1, GSTA1, GSTM1, and GSTT1 gene polymorphisms to oral cancer risk.
In conclusion, the GSTM1 null genotype may be associated with a higher risk of oral cancer in Asians but not in Caucasians, and this effect may be modified by smoking status.
GSTT1 null and rs1695 were inversely associated with oral leukoplakia while GSTM1 null, GSTT1 null, rs2031920, rs3813867 (CYP2E1), and rs13181 were associated with OC.