Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

BACKGROUND: Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking. METHODS AND RESULTS: Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility. CONCLUSIONS: A combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2'-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

Genetic instability in peripheral lymphocytes as biological marker for non-small cell lung cancer patients in the South Indian state of Andhra Pradesh.

OBJECTIVES: This study aims, first, at evaluating the DNA and chromosomal damage in non-small cell lung cancer (NSCLC) patients from the South Indian state of Andhra Pradesh, and then at correlating these results with possible confounding factors that might potentially play a role in causing genetic damage. METHODS: The study included 246 NSCLC patients (177 men and 69 women) and 250 healthy controls (180 men and 70 women) for the analysis of DNA and chromosomal damage using the comet assay and micronucleus test. RESULTS: Both DNA and chromosomal damage were found to be increased in NSCLC patients compared to healthy controls, and the extent of the damage was higher in males than female patients. The smoking status had a profound effect on the extent of DNA and chromosomal damage in NSCLC patients. The degree of genetic damage correlated with the stage of the disease. However, the histological status had no effect on the extent of DNA and chromosomal damage among NSCLC patients. CONCLUSIONS: We here report, for the first time, that the NSCLC patients selected form the Andhra Pradesh population had increased DNA damage and higher mean micronucleus frequencies in peripheral lymphocytes, indicating a strong background level of genetic instability.

Evaluation of oxidative stress and DNA damage in traffic policemen exposed to vehicle exhaust.

OBJECTIVE: We aimed to study the genotoxic effects in traffic police who are occupationally exposed due to higher free radical generation. METHODS: Ambient and breathing zone air samples were analyzed blood samples were collected for analysis of antioxidant enzymes Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and free radicals - nitric oxide (NO) and malondialdehyde (MDA) levels using a spectrophotometer. DNA damage was measured with the comet assay. RESULTS: Higher levels of benzene (BZ), toluene (TOL), carbon monoxide (CO), benzo([a])pyrene (BaP) and sulfur dioxide (SO2) was observed in traffic police. Elevated levels of NO, MDA and comet tail length and lower SOD and GPx levels observed in traffic police. CONCLUSION: The studied biomarkers, related to oxidative stress and DNA damage positively correlated in traffic police exposed to environmental air pollutants.

Assessment of 8-oxo-7, 8-dihydro-2'-deoxyguanosine and malondialdehyde levels as oxidative stress markers and antioxidant status in non-small cell lung cancer.

OBJECTIVE: The present investigation was taken up to evaluate the 8-oxo-7,8-dihydro-2'-deoxyguanosine and malondialdehyde as markers of oxidative stress, the levels of antioxidants and the correlations between these oxidative stress markers and antioxidants in lung cancer patients. METHODS: The study included 222 patients (158 men and 64 women, age ranging from 32 to 85 years) and 207 control subjects (153 men and 54 women, aged 30-80 years) for the analysis of urinary excretion of 8-oxodG using an ELISA assay, plasma malondialdehyde using spectrophotometer and red cell Cu-Zn SOD and GPx activities by kit methods. RESULTS: The levels of 8-oxodG and malondialdehyde were significantly higher (p < 0.001) and red cell superoxide dismutase and glutathione peroxidase activities (p < 0.001) were significantly lower in lung cancer patients than in controls. There was a significantly positive correlation between 8-oxodG and malondialdehyde (r=0.912, p < 0.001) and a negative correlation between 8-oxodG and antioxidants. CONCLUSIONS: Our results demonstrate that an increased rate of oxidative stress might play a role in the pathogenesis of lung cancer as evidenced by a failure in the oxidant/antioxidant balance in favour of lipid peroxidation and DNA damage.

Role of connexin 26 (GJB2) & mitochondrial small ribosomal RNA (mt 12S rRNA) genes in sporadic & aminoglycoside-induced non syndromic hearing impairment.

Non syndromic hearing impairment is a common sensory disorder, which affects one in 600 newborns. Though more than 50 nuclear genes are involved in causing non syndromic hearing impairment, mutations in the connexin 26 (GJB2) gene explain a high proportion of congenital deafness in several populations worldwide. The diversity of genes and genetic loci implicated in hearing loss defines the complexity of the genetic basis of hearing. This review focuses on the role of connexin 26 and mitochondrial 12S rRNA genes in hearing which will be helpful for better understanding of genes in sporadic and aminoglycoside-induced non syndromic hearing impairment.