GSTM1 null genotype was found to be associated with lung cancer (OR=1.65, 95%CI: 116-2.3, P=0.005) and this risk was higher in cases of adenocarcinoma (ADCC).
Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype.
In presented case-control study we investigate the incidence of polymorphism of GSTT1, GSTM1, GSTP1 genes and their combinations as possible predictive factors for identification of individuals with increased risk of formation and development of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of lung in Slovak population.
The impact of combined genotypes of the CYP1A1 Ile/Val polymorphism and GSTM1 on mutation of K-ras was also analyzed, and a higher risk of having a mutated K-ras gene was found for both the CYP1A1 Ile/Ile and GSTM1(-) (OR, 6.32; p=0.021; 95% CI, 1.33-30.19) and CYP1A1 Ile/Val and GSTM1(-) (OR, 6.09; p=0.042; 95% CI, 1.07-34.72) genotype combinations in patients with adenocarcinoma.
The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD).
GSTM1 absence was associated with a modest elevation in risk among all cases (odds ratio=1.27, 95% CI 0.91-1.77) and among non-small cell cancers (adenocarcinoma OR=1.58, 95% CI 0.99-2.52; squamous cell OR=1.40, 95% CI 0.83-2.34).
Mutations of the K-ras gene were detected in 6 of 100 (6%) and 15 of 93 (16.1%) adenocarcinoma cases with the GSTM1(+) and GSTM1(-) genotypes, respectively, and the difference was statistically significant.
In this case-control study (consisting of 389 Caucasian lung cancer patients, including 151 adenocarcinomas (ACs) and 172 squamous cell carcinomas (SCCs), and 353 hospital control subjects without malignant disease, genotype frequencies for GSTM1, GSTM3, GSTP1 and GSTT1 were determined by polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP)-based methods.
Among AC and SCC cancer patients, individuals with the GSTM1-null genotype had an OR of 1.80 (95% CI, 1.1-2.8; case-only analysis) of having AC versus SCC if they also carried a p53 Pro allele.
GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas.
We tested the hypothesis that genetic susceptibility to PAHs, as determined by polymorphisms in CYP1A1 and GSTM1, predominantly causes lung SCCs, and susceptibility to nitrosamines, as determined by polymorphisms in CYP2E1, predominantly causes lung ACs.
The frequency of the null GSTM1 gene was 42.3% among the lung cancer patients with no preferential tendency towards developing squamous cell carcinoma versus adenocarcinoma (OR = 1.10, 95% CL = 0.3-4.14, P = 0.5).
We found: (1) that in squamous and small cell carcinomas GSTM1 null genotype distributed markedly more in females than males especially among the patients aged < 70 years (male 57.4%, female 100.0%); (2) that GSTM1 null genotype distributed generally more in patients aged < 70 years (58.3%) than those aged > or = 70 years (50.0%) irrespective of histologies except for small cell carcinoma; and (3) that proportion of GSTM1 null genotype increased dependent on the extent of tobacco smoke exposure in male patients having squamous and small cell carcinomas aged < 70 years, and remained high but independent of the smoking index in adenocarcinoma and unchanged in never- or exsmokers from the control level (48.6%).
Furthermore, when male patients and controls were analysed in relation to the degrees (< 800, 800-1200 and > or = 1200) of smoking index (sigma (cigarettes smoked per day) x (years of smoking)], the proportion of GSTM1 null genotype was found to increase progressively in the squamous and small cell carcinoma groups from 42-50% (odds ratio 0.8-1.3) in the patients with smoking index < 800 to 72-75% (odds ratio 3.1-3.7) in the patients with smoking index > or = 1200, while it was unrelated in the adenocarcinoma (50-55%, odds ratio 1.2-1.5) and in the control groups (42-48%).
The highest proportion of the GSTM1(-) genotype was found in patients diagnosed with adenocarcinoma (63%, 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female squamous cell carcinoma patients (79%, 15/19).