Our findings suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 may be the risk alleles for oral cancer susceptibility in Pashtun population.
For GSTM1 gene, null genotype appeared to be a risk factor for oral cancer (null vs present: OR 1.23, 95% CI 1.12-1.34), which was also proved in the subgroup analysis.The results demonstrated that CYP1A1rs4646903 and null genotype of GSTM1 polymorphisms might serve as risk factors for oral cancer.
Among these 14 variants, 9 variants were reported to be significantly associated with the risk of oral cancer (CYP1A1-MspI, CYP2E1-RsaI/PstI, MTHFR-C677T, p73-G4C14-to-A4T14, XRCC1-Arg194Trp, CYP1A1-Ile462Val, GSTM1-±, and NAT2 slow vs rapid).
The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk.
This meta-analysis indicated a marked association of CYP1A1*2A polymorphisms with oral cancer risk, particularly among Asians, whereas there were significant interactions between the polymorphisms and cigarette smoking on oral cancer risk.
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.
Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5).
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.
In conclusion, our results suggest that polymorphism in CYP1A1 m2 gene and/or GSTM1 and GSTT1 null genotype may confer an increased risk for oral cancer.
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).
These results also suggest that individuals with the CYP1A1 exon 7 ile:val polymorphism are at increased risk for oral cancer, and that this risk may not be influenced by differences in exposure to tobacco smoke.