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Glutathione s-transferase genotypes as risk factors for head and neck cancer
Z Trizna1, G L Clayman, M R Spitz
1University of Texas M.D. Anderson Cancer Center, Department of Head and Neck Surgery, Houston 77030, USA.
Background:
Several enzymatic systems, including glutathione S-transferases, are involved in the metabolism of environmental agents. The absence of glutathione S-transferases mu (GSTM1) and theta (GSTT1) results in decreased detoxification of carcinogens, for example, chemicals in cigarette smoke. These metabolic deficiencies may predispose individuals to the development of smoking-related tumors, such as cancers of the lung, head and neck, and bladder.
Methods:
The glutathione S-transferase genotypes of 186 previously untreated patients with squamous cell carcinoma of the head and neck and 42 healthy controls were determined with polymerase chain reaction (PCR) methodologies. Lymphocytes separated from heparinized peripheral blood or whole blood extracts served as sources of genomic DNA. The presence or absence of the gene-specific PCR products revealed the positive or negative genotypes, respectively.
Results:
The absence of the GSTM1 genotype conferred an odds ratio of 2.37, and the 95% confidence interval (CI) was 1.20 to 4.67. The absence of the GSTT1 gene conferred an odds ratio of 1.47 (CI 0.71 to 3.02). In the population of 42 patients and their matched 42 controls, the absence of the GSTM1 and GSTT1 genotypes conferred odds ratios of 3.10 (CI 1.24 to 7.75) and 2.18 (CI 0.91 to 5.23), respectively.
Conclusions:
Despite the small study size, our preliminary data suggest that genetically determined factors of carcinogen metabolism may be associated with increased risk for head and neck cancer.
Insights
Genetic variations in detoxification enzymes like glutathione S-transferases mu (GSTM1) and theta (GSTT1) may increase head and neck cancer risk. Absence of these enzymes is linked to higher susceptibility to carcinogens found in cigarette smoke.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Glutathione S-transferases (GSTs) are key enzymes in metabolizing environmental agents.
- Deficiencies in GSTM1 and GSTT1 reduce carcinogen detoxification, potentially increasing cancer risk.
- This is particularly relevant for smoking-related cancers like lung, head and neck, and bladder cancer.
Purpose of the Study:
- To investigate the association between GSTM1 and GSTT1 genotypes and the risk of head and neck squamous cell carcinoma.
- To determine if genetic variations in carcinogen metabolism influence susceptibility to head and neck cancer.
Main Methods:
- Genotyping for GSTM1 and GSTT1 was performed using polymerase chain reaction (PCR) on 186 head and neck cancer patients and 42 controls.
- Genomic DNA was extracted from lymphocytes or whole blood.
- Presence or absence of PCR products indicated positive or negative genotypes, respectively.
Main Results:
- Absence of the GSTM1 genotype was associated with an odds ratio of 2.37 (95% CI 1.20–4.67).
- Absence of the GSTT1 genotype showed an odds ratio of 1.47 (95% CI 0.71–3.02).
- In a matched subgroup, absence of GSTM1 and GSTT1 conferred odds ratios of 3.10 (95% CI 1.24–7.75) and 2.18 (95% CI 0.91–5.23), respectively.
Conclusions:
- Preliminary findings suggest a link between genetically determined carcinogen metabolism and head and neck cancer risk.
- These genetic factors may play a role in individual susceptibility to developing head and neck tumors.
- Further research with larger sample sizes is warranted to confirm these associations.