In the first, involving a U.S. population sample, smokers with and without lung cancer were phenotyped, and a highly significant correlation between the absence of GSTM1-1 activity and adenocarcinoma of the lung was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians.
A synergistic increase in susceptibility to lung cancer was observed when the susceptible genotypes of CYP1A1 were combined with a deficient GSTM1 genotype.
GSTM1 gene deficiency has been shown to occur in approximately half of the populations of various ethnic origins and has been implicated as a factor for elevated risk for lung cancers.
Combined CYP1A1 and GSTM1 genotype is thus a potential predictor of genetic susceptibility to smoking-related lung cancers in populations where CYP1A1 m2 or Val alleles are common.
The risk of developing lung cancer is dramatically (up to 40-fold) elevated in subpopulations having simultaneously high-risk genotypes in CYP1A1 and GSTM1.
This imbalance in the metabolism of carcinogens may explain the increased susceptibility to lung cancer reported in smokers with the GSTM1 null genotype.
The glutathione S-transferase M1 (GSTM1) genotypes of the patients were determined, since the GSTM1 null genotype has been associated with increased susceptibility to lung cancer and chemically induced cytogenetic damage.
The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles.
Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined.
In patients with inducible CYP1A1, the expressing GSTM1 gene appeared to have a protective effect against contracting bronchial lung cancer, since 88% (14/16) of the lung tumours in this patient group were peripheral, whereas almost equal numbers of peripheral and bronchial tumours were observed in those patients lacking the gene (P = 0.037).
A synergistic increase in susceptibility to lung cancer was found when combining genotyping of CYP1A1 and the Mu-class of glutathione S-transferase (GST1).
These results support the hypothesis that the GSTM1 null genotype is one of the genetic traits for smoking-related lung cancers, the risk of which, however, appears to be dependent on the extent of tobacco smoke exposure.
Although the increased risk is small, GSTM1 deficiency accounts for approximately 17% of lung cancer cases because of the high prevalence of GSTM1 deficiency.
In addition, a possible interaction was observed between smoking and GSTM1 genotype in the CA assay, GSTM1 null smokers, earlier reported to have an elevated risk for lung cancer, showing higher CA frequencies than GSTM1 positive smokers.
An association between the presence of this transversion and the genotype deficient in glutathione S-transferase M1-mediated detoxification has been observed in lung cancer.
The proportion of the GSTM1 gene deletion genotype was estimated as significantly increased in LC (81%), OT (65%), E (81%), AC (77.3%), and in CB (73.6%) patients with symptoms of CB confirmed by X-ray but not in CB patients without X-ray evidence of disease (40.9%).
In this study, the involvement of three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in the development of different histological types of lung cancer was investigated.
Increased risk of lung cancer has been reported in individuals with glutathione S-transferase M1 (GSTM1) gene deletion, with limited evidence for head and neck (HN) cancer.
The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51].
Gene deletion at the glutathione S-transferase mu locus (GSTM1) has previously been associated with increased risk for environmentally-induced cancers (e.g. smoking-related lung cancer).
After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4).