The present study investigates the polymorphic genotypes of the most important XME, glutathione-S-transferase Mu 1 (GST M1) and Theta 1 (GST T1) as the risk modulator to HNC among tobacco-habituated inhabitants of Saurashtra in Gujarat, a region in western India.
The current review gives a complete study overview regarding CYP1A1, GSTM1, GSTT1 and GSTP1 variations at DNA, mRNA and protein levels in head and neck cancer.
In this study we investigate the association of A313G and C341T GSTP1 polymorphisms, GSTM1 and GSTT1 null genotypes in the head and neck cancer development, interactions between these polymorphisms,the tumor histopathologic parameters and risk factors (smoking and drinking) were also evaluated in the case-control study.
Undetectable or partial loss of expression of GSTM1 and GSTT1 mRNA was also observed at a higher rate in head and neck cancer tissue compared to control (OR 4.5, CI 1.5- 13.4 and OR 3.2, CI 1.1- 9.6 respectively).
Multifactor dimensionality reduction approach showed that the three-factor model, including smoking status, CYP1A1 T3801C, and GSTM1 copy number variants, conferred more than fourfold increased risk of head and neck cancer (odds ratio 4.89; 95% confidence interval: 3.15-7.32, p < 0.01).
Our findings corroborate metabolic genes interactions, especially for CYP1A1 462Val alleles and GSTM1 homozygous deletion, in the development of head and neck cancer in the investigated population groups in Poland.
GSTM1, GSTT1, GSTP1, XRCC1 codons 194 and 399, and CYP1A1 codon 462 were examined by meta-analyses, and significant relations were found between the GSTM1-null genotype and an increased risk for HNC.
A significant association between head and neck cancer and GSTM1 null genotype was observed both considering benign disease controls (p=0.001, OR=2.613; 95% C.I.=1.48-4.62), and healthy donors (p=0.0003, OR=3.35; 95% C.I.
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.
The studies done so far for GSTM1 null genotype as a risk factor associated with head and neck cancer are not conclusive and have shown conflicting results.
Total GST enzyme activity was significantly lower in patients with HNC (208 +/- 9 micromol/min*l) than in controls (264 +/- 11 micromol/min*l, P< 0.0001) but did not depend on GSTM1-genotype (P = 0.1).
In conclusion, both the meta- and pooled analysis support modest associations of GSTM1 and GSTT1 genotypes with head and neck cancer risk, and our pooled analysis supports the notion of greater risk when genotypes at multiple GST loci are considered in a multigenic model.
Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer.
GSTM1 and GSTT1 null genotypes as well as polymorphic variants in the CYP1A1 gene that may help determine the risk for head and neck cancer have been described in previous reports.