'Is It Brain Talking to the Ear': Neuro-otological Evaluation of Tinnitus Using Auditory Brainstem Response Audiometry.

Tinnitus is hypothesized to be an auditory phantom phenomenon resulting from spontaneous neuronal activity somewhere along the auditory pathway. The neural abnormalities underlying tinnitus are largely unknown. We evaluated the functional characteristics and the auditory system synchronization using Auditory Brainstem Response (ABR) in normal hearing tinnitus patients. In this observational comparative cross-sectional study, patients with chief complaints of Tinnitus and equal number of age and sex matched controls without hearing loss and tinnitus were enrolled. All patients underwent a full ENT assessment, pure tone audiometry and Brainstem evoked response audiometry (BERA) tests. The study population consisted of 100 patients with tinnitus, 55 controls without tinnitus and 45 controls with tinnitus. Statistical analysis showed significant relation (p < 0.05) between hearing loss and tinnitus between cases and controls with tinnitus, between absolute latency of wave III amongst cases and controls without tinnitus, Interpeak Latency between wave III and V amongst cases and controls with tinnitus and interpeak latency of wave I and wave III amongst controls without and with tinnitus. Brainstem evoked response audiometry results that we obtained from the patients of tinnitus and controls with and without tinnitus are different from one person to another. This suggests impaired neural firing synchronization and transmission in the central auditory pathway in tinnitus patients. These findings also indicate that the pathology underlying tinnitus is not the same in every individual, with possible brainstem involvement in some cases.

A Short Term Comparison of Cartilage with Temporalis Fascia Graft Tympanoplasty in Paediatric and Adolescent Population.

To compare the anatomic and functional outcomes of the cartilage and temporalis fascia graft materials in type 1 tympanoplasty in paediatric and adolescent population. A total of 55 patients aged <18 years who required type 1 tympanoplasty were selected. 30 patients underwent cartilage palisade tympanoplasty and 25 using temporalis fascia grafts. The age, the side of the operated ear, the operative technique, pre- and post operative pure tone and impedance audiological results, and the status of the graft were noted. Graft was considered taken up if there was successful closure of tympanic membrane perforation. At the end of 6 months, the graft take rate for cartilage was 90% and for temporalis fascia it was 80% (p > 0.05). ABG closure ratio in cartilage group was 58.54 ± 23.10% and in temporalis fascia group was 56.46 ± 27.4% (p > 0.05). Pre operatively all patients had type B tympanogram in both the groups. While post operatively either type A or C curve was seen in 80% patients of cartilage and 68% patients of temporalis fascia group. Hearing outcomes and graft success rates were high in both fascia and cartilage graft groups but not significantly different.

Morphometric Analysis of the External Auditory Canal by Computed Tomography in Indian Population.

Various studies have shown variations in size and shape of different anthropometric measurements of external auditory canal. We conducted an anthropometric study of the three-dimensional anatomy of the osseous external auditory canal (OEAC) using high-resolution computed tomography the temporal bone to identify the variations in subset of Indian population from North India. A retrospective review of high-resolution computed tomography images of the temporal bones of 125 patients (250 external auditory canals) of different ages (mean 28.43 years) acquired from September 2014 to February of 2015 was performed. Using a method, as proposed by Mahboubio et al. (Otol Neurotol 33:715-720, 2012), six defined dimensions of the OEAC in the parasagittal planes were recorded at the level of annulus, midcanal and the outermost point of osseous external auditory canal at bony-cartilaginous junction. The length and shape of the OEAC were also studied and the frequency rate of each was recorded. The most prevalent shape of the OEAC was found to be conical (64%) and the mean osseous external auditory canal length was 9.61 mm. The length of the OEAC was significantly different between ages above and below 12 years while the 6 defined cross sectional dimensions were statistically significant between ages above and below 8 years. The history of chronic suppurative otitis media had a significant bearing on the inferior mid-anteroposterior dimension at the level of bony-cartilaginous junction. There was statistically significant difference in supero-inferior diameter in the posterior half at the level of mid-canal and outer bony-cartilaginous junction between males and females. The comprehensive set of standardized measurements collected in this study provides three-dimensional information on osseous external auditory canal geometry. These measurements and the methodology will contribute to the development of element models of the osseous canal for computational modeling purposes and also provide important measurements for design of in-the-canal hearing aids, specialized earplugs and for defining average sizes for canalplasty procedures, in pre- and postoperative surgical planning and assessment of canal atresia and stenosis in Indian population. No such previous study has been done in North Indian population.

Cartilage palisades in type 3 tympanoplasty: functional and hearing results.

To evaluate the functional and hearing outcomes using full thickness broad cartilage palisades for tympanic membrane reconstruction in type 3 tympanoplasty with titanium prostheses. The retrospective study performed at a tertiary referral institute included 30 patients with posterior mesotympanic retraction pockets or tympanic membrane perforations requiring tympanic membrane and type 3 ossicular reconstruction. Patients with disease extending beyond the aditus requiring canal wall down mastoidectomy were excluded. Disease removal from posterior mesotympanic and epitympanic recesses was confirmed using angled endoscopy and ossicular reconstruction was performed using titanium partial or total ossicular replacement prostheses. Tympanic membrane reconstruction was done, with or without attic reconstruction, using full thickness broad cartilage palisades harvested from the tragus with perichondrium attached laterally. Patients were assessed at 24 and 48 weeks for graft status and any evidence of implant extrusion. Hearing evaluation was done using subjective assessment and pure tone audiometry. In total, 27 out of 30 patients had intact and completely healed grafts at 48 weeks postoperatively (a success rate of 90 %) showing full union and epithelialization of palisades, and with three patients displaying small defects. The mean pure tone air bone gap pre- and postoperatively was 32.4 and 8.8 dB, respectively, with most patients reporting satisfactory postoperative hearing. No evidence of implant extrusion was found in the 48-week period. Tympanic membrane reconstruction using full thickness palisades of tragal cartilage provides good functional and hearing outcomes in type 3 tympanoplasty with titanium prostheses.

Giant vascular hamartoma of the tongue.

We present one of the largest lingual hamartomas of the tongue base to have been reported, along with a review of the current literature and a description of the management of this case, as well as insights into the histopathology of the lesion. A 21-year-old woman presented with a mass on the base of her tongue, extending to the vallecula. The mass was found to be over 4 cm and enhancing on computed tomography. The size, vascularity, and site of the lesion merited its excision using the suprahyoid pharyngotomy approach. Histopathology confirmed the mass to be a vascular hamartoma. In reviewing the literature, we encountered 61 reported cases of lingual hamartomas, which are described with a number of pathological variants and sites of occurrence and with different methods of surgical excision. The size, vascularity, and site of the lesion we found merited a different approach from the conventional transoral approach that was used in all of the previous reports. Also, our study agrees with current world literature that histopathological examination plays an important role in the final diagnosis.

Extensive nasopharyngeal angiofibromas: the maxillary swing approach.

The objective of this study was to evaluate the efficacy and outcome using the maxillary swing approach for the management of extensive nasopharyngeal angiofibromas. A retrospective analysis in a tertiary care center revealed five cases with extensive nasal angiofibromas operated using the maxillary swing approach between 2010 and 2012. All patients had tumor extension to the lateral-most portions of the infratemporal fossa with complete occupation and destruction of the lateral wall of the sphenoid sinus causing abutment to the cavernous sinus and complete involvement of the pterygopalatine fossa and pterygoid base. One patient displayed full occupancy of the maxillary sinus as a consequence of erosion of the posterior and medial walls of the maxillary sinus, while another had severe temporal lobe compression through the roof of the infratemporal fossa. All patients underwent tumor excision using the maxillary swing approach. Patients were followed up for a minimum period of 1 year after surgery. The maxillary swing approach gave optimal exposure of the entire central skull base including the infratemporal fossa and its extreme lateral and superior aspects. Adequate tumor exposure and vascular control could be achieved in all cases resulting in complete tumor excision. The mean operative time was 4.5 h. Post-operative healing was satisfactory with palatal fistula formation in two cases and all patients remaining disease-free up to the present time. One had minimal misalignment of the halves of the upper jaw and two had epiphora, of which one required dacryocystorhinostomy. The maxillary swing is an effective approach in the management of extensive nasopharyngeal angiofibromas and leads to optimal anatomical exposure with minimal morbidity.

Polymorphism Arg72Pro of p53 confers susceptibility to squamous cell carcinoma of lungs in a North Indian population.

The causes of lung cancer might be many, but genetic variation in the genes of carcinogen-metabolizing enzymes, tumor suppressor proteins, and/or DNA-repairing enzymes can also play a significant role in lung cancer susceptibility. The tumor suppressor protein p53 functions to induce cell cycle arrest, DNA repair, or apoptosis. Polymorphism in its gene can, therefore, play a significant role in cancer susceptibility. Present report evaluated the association of polymorphism in exon 4 Arg72Pro (G>C) of the p53 gene with lung cancer susceptibility using 175 cancer cases and 202 controls from the North Indian population. Binary logistic regression analysis revealed that the Pro72Pro genotype was significantly associated with increasing risk for lung cancer in younger age patients (≤55 years) (adjusted odds ratio [OR]=2.72, 95% confidence intervals [95% CI] 0.99-7.85, p<0.05). Histological stratification of lung cancer revealed that the Pro72Pro genotype was associated with higher risk for squamous cell carcinoma (OR=3.05, 95% CI 1.07-8.87, p<0.05). Genetic variation Arg72Pro of the p53 gene may contribute to higher risk of SCC of lung in the North Indian population.

Expression of P-glycoprotein is positively correlated with p53 in human papilloma virus induced squamous intraepithelial lesions of uterine cervix: poor prognosis association.

This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.

Studies on oxidative stress induced nerve conduction deficits in cigarette smokers.

An important role of oxidative stress for the development of vascular and neurological complications has encouraged us to undertake a study to assess the oxidative stress induced nerve conduction deficits among cigarette smokers. Eighteen regular male cigarette smokers and twenty nine male non-smokers were diagnosed for clinical neuro-physiological tests viz., motor and sensory nerve conduction velocity (MNCV and SNCV) and redox status. Significant depletion of reduced glutathione (GSH) level (p < 0.05) and significant increase in malondialdehyde (MDA) level (p < 0.01) was found in smokers compared to non-smokers. Motor and sensory nerve conduction velocity showed no significant difference among smokers compared to non-smokers. The present study shows that smoking can induce oxidative stress among smokers but could not exacerbate to nerve conduction deficits.

Association of functionally important polymorphism of microsomal epoxide hydrolase gene (EPHX1) with lung cancer susceptibility.

Distribution and gene-environment interaction of EPHX1 polymorphism was evaluated in 175 lung cancer patients and 322 controls from north India. Two novel non-synonymous, Lys117Arg and Leu263Phe, and twelve single nucleotide polymorphisms were identified in the present study. Binary logistic regression analysis showed association of polymorphism Tyr113His with increased risk of lung cancer (OR = 2.2, 95% CI = 1.2-4.0, p < .05). Gene-environment interaction revealed that patients with His113His and smoking habit had significantly greater risk of lung cancer (OR = 4.52, 95% CI = 0.93-43.05, p < .05). Present study provided evidence that EPHX1 polymorphism is associated with lung cancer susceptibility in Indian population.

Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men.

The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.

Co-expression of p53 and Bcl-2 proteins in human papillomavirus-induced premalignant lesions of the uterine cervix: correlation with progression to malignancy.

OBJECTIVE(S): To analyze aberrant expression of the apoptotic protein p53 and the anti-apoptotic protein Bcl-2 in premalignant lesions of the uterine cervix induced by human papillomavirus (HPV) infection and its significance for early diagnosis of cervical cancer. MATERIALS AND METHODS: Cytological adequate smears (n = 382) from various grades of squamous intraepithelial lesions (SILs; n = 142), 'atypical squamous cells of unknown significance' (ASCUS; n = 128) and normal tissue (n = 112) were investigated immunocytochemically for aberrant expression of p53 and Bcl-2 proteins using the streptavidin-biotin-peroxidase method; HPV status was analyzed in cervical smears using general and type-specific primers. RESULTS: HPV-DNA of any type was detected in 25.7% (98/382) of cases. HPV16 was seen in 58.2% (57/98), HPV18 in 20.4% (20/98) and other HPV types in 21.4% (21/98). Abnormal nuclear expression of p53 protein and cytoplasmic expression of Bcl-2 protein were noted in cervical dysplasia and an association with the presence of HPV16/HPV18 was noted. The intensity of immunoreactivity for p53 and Bcl-2 proteins varied between different cytological grades of cervical smears. Follow-up data revealed that cases with high-risk HPV and co-induced expression of apoptosis-regulatory proteins presented a trend to progressive disease. CONCLUSIONS: The detection of both p53 and Bcl-2 proteins in cervical smears can be used as independent diagnostic marker for early-stage HPV-associated cervical cancer.

Adverse health effects of pesticides in agrarian populations of developing countries.

Developing countries use only 20% of the world's agrochemicals, yet they suffer 99% of deaths from pesticide poisoning. Pesticide poisoning is a significant problem in developing countries primarily because of unsafe pesticide application and handling practices. Safety is further exacerbated by the illiteracy and poverty that prevails in most farming communities of developing countries. Pesticides classified as being extremely or highly hazardous by FAO and WHO, including those banned by other countries, continue to be used in developing countries. Many farmers in developing countries continue to be exposed to pesticides from either storing them in or near their residences, or from inadequate or unsafe application or handling practices. Farming populations exposed to pesticides suffer from several health problems, primarily neurological abnormalities, respiratory ailments, and reproductive, endocrinological, and dermal problems. In developing countries, the scientific literature (including the Indian Institute of Toxicology Research, India) have taken the initiative to monitor health problems resulting from pesticide exposure in agrarian communities. The welfare fund for agricultural laborers could institute a special program for pesticide applicators in developing countries. The primary need, currently, in such countries is creation and implementation of sound national policies to effectively articulate appropriate guidelines for managing farm pest control activities. Such policies should be aimed at both limiting pesticide exposure and usage, but doing so without damaging the yields of food production. If such steps are taken, it is fully expected that the incidence of adverse health consequences for agrarian populations from pesticide toxicity will decrease, and the health of farmers improve.

Polymorphism in cytochrome P4501A1 is significantly associated with head and neck cancer risk.

A case control study was undertaken to investigate the association of polymorphisms in cytochrome P4501A1 (CYP1A1) with squamous cell carcinoma of head and neck (HNSCC) in North Indian population. The variant genotypes of CYP1A1*2A and CYP1A1*2C were found to be overrepresented in cases when compared to controls. The HNSCC risk also increased several folds in cases with combination of variant genotypes of CYP1A1*2A or CYP1A1*2C with null genotype of glutathione-S-transferase M1 (GSTM1), a phase II enzyme, particularly in cases who were tobacco users (smokers and tobacco chewers), demonstrating the role of gene-gene and gene-environment interactions in the development of HNSCC.

Evidence for increased cytochrome P450 1A1 expression in blood lymphocytes of lung cancer patients.

To develop blood lymphocyte cytochrome P450 1A1 (CYP1A1) expression as a surrogate for monitoring tissue expression for polycyclic aromatic hydrocarbon (PAH) induced toxicity, the present study attempted to characterize CYP1A1 mRNA expression and its associated catalytic activity in freshly prepared blood lymphocytes isolated from healthy controls and patients suffering from tobacco induced lung cancer. Human blood lymphocytes were found to express CYP1A1 mRNA and significant activity of 7-ethoxyresorufin-O-deethylase (EROD). Significant increase in the activity of EROD and CYP1A1 mRNA was observed in blood lymphocytes isolated from patients suffering from lung cancer. Further, controls with variant genotypes of CYP1A1 (Msp1 or Ile/Val polymorphism) exhibited significant increase in the enzyme activity associated with an increase in CYP1A1 mRNA expression when compared to the controls with wild type genotype. Patients with variant genotypes of CYP1A1 also exhibited much greater increase in the blood lymphocyte CYP1A1 mRNA expression and EROD activity when compared to controls or patients with wild type genotype. Our data thus provides evidence of CYP1A1 expression in freshly isolated blood lymphocytes and differences in reactivity in individuals with variant genotypes of CYP1A1, suggesting that blood lymphocyte CYP1A1 expression profile could help in identifying individuals at risk to environment induced lung cancer.

Association of poor metabolizers of cytochrome P450 2C19 with head and neck cancer and poor treatment response.

A case-control study consisting of 300 patients and an equal number of healthy controls was carried out to investigate the association of polymorphism in cytochrome P450 2C19 (CYP2C19), which results in poor and extensive metabolizers (PMs and EMs) genotypes, with squamous cell carcinoma of head and neck (HNSCC) and treatment response in patients receiving combination of chemo-radiotherapy. A higher frequency of CYP2C19 2 variants was observed in the cases resulting in significantly higher risk to HNSCC (Ad OR 3.36, 95% CI 1.94-5.82, p-value<0.05). The PM genotype of CYP2C19 3 was also found to be slightly increased in the cases, though the increase in risk was not significant when analyzed by multivariate logistic regression model. Tobacco chewing amongst the cases resulted in almost 13-fold increase in the risk with CYP2C19 2 (OR: 12.39) and 3-fold with CYP2C19 3 genotype (OR: 2.90) when compared to the tobacco chewers amongst the controls. Likewise, cigarette smoking in the cases increased the risk approximately 9-fold and 3-fold with CYP2C19 2 (OR: 8.93) and CYP2C19 3 (OR: 2.18) genotypes respectively when compared to smokers amongst the controls. Similar increase in risk was associated with alcohol use amongst the cases carrying variant genotypes of CYP2C19 2 (OR: 7.75) or CYP2C19 3 (OR: 2.60), demonstrating the importance of gene-environment interaction in modifying susceptibility to HNSCC. Interestingly, patients with PMs of CYP2C19 (CYP2C19 2 and CYP2C19 3) exhibited little response to the respective chemotherapy than the patients carrying wild-type genotype demonstrating that functional enzyme deficiencies due to polymorphism in CYPs may not only be important in modifying the susceptibility to HNSCC but also in determining chemotherapeutic response.

Association of functionally important polymorphisms in cytochrome P4501B1 with lung cancer.

In the present study, genotype and haplotype frequencies of four polymorphisms of cytochrome P450 1B1 (CYP1B1) that cause amino acid changes (Arg-Gly at codon 48, Ala-Ser at codon 119, Leu-Val at 432 and Asn-Ser at codon 453) were studied in 200 patients suffering from lung cancer and equal number of controls. A significant difference was observed for the distribution of variant genotypes of CYP1B1Arg48Gly and Ala119Ser polymorphisms (CYP1B1*2) in cases when compared to the controls. No significant difference was observed for the distribution of variant genotypes of CYP1B1Leu432Val (CYP1B1*3) and CYP1B1Asn453Ser (CYP1B1*4) polymorphism. When the four SNPs were analyzed using a haplotype approach, SNPs at codon 48 (Arg48Gly) and codon 119 (Ala119Ser) exhibited complete linkage disequilibrium (LD) in all the cases and controls. Significant differences in the distribution of the three haplotypes (G-T-C-A, G-T-G-A and G-T-C-G) were observed in the cases when compared to controls. Tobacco use in the form of smoking as well as chewing was found to significantly increase the risk of lung cancer in patients by interacting with CYP1B1Ala119Ser genotypes demonstrating the role of gene-environment interaction in lung cancer. Further, the risk of lung cancer increased several fold in the patients carrying the genotype combinations of CYP1B1Ala119Ser and CYP1B1Leu432Val with GSTM1, a phase II enzyme suggesting the importance of gene-gene interactions in enhancing the susceptibility to lung cancer.

Association of genetic polymorphisms in glutathione S-transferases and susceptibility to head and neck cancer.

Polymorphism in glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1) and interaction with environmental factors such as tobacco (smoking or chewing) and alcohol on susceptibility to head and neck squamous cell carcinoma (HNSCC) was studied in a case-control study. The study group consisted of 175 patients suffering from HNSCC and 200 age matched healthy controls. Statistical analysis showed an increase in risk to HNSCC in the patients with null genotype of GSTM1 (OR: 2.02; 95% CI: 1.32-3.10; P=0.001) or GSTT1 (OR: 1.66; 95% CI: 1.02-2.69; P=0.04), though the risk was not found to be significant when adjusted for age, sex, smoking, tobacco chewing or alcohol use by multivariate logistic regression model. Our data further showed that combination of deletion genotypes of GST (GSTM1 and GSTT1) confer an even higher risk of HNSCC. Interestingly, GSTP1 wild type genotype in combination with GSTM1 null or GSTT1 null genotype increased susceptibility for HNSCC (OR: 2.49 and 2.75, respectively). Likewise a much greater risk for HNSCC was observed in the patients carrying a genotype combination of GSTM1 null, GSTT1 null and GSTP1 (Ile/Ile) (OR: 4.47; 95% CI: 1.62-12.31; P=0.002). Our data have further provided evidence that tobacco chewing and alcohol consumption are the important risk factors for HNSCC. The interaction between tobacco chewing and null genotype of GSTM1 or GSTT1 resulted in about 3.5- and 2.2-fold increase in the risk respectively in the patients when compared to those not chewing tobacco. Alcohol use resulted in more than 4-fold increase in the risk in the patients with null genotype of GSTM1 as compared to those who are non-drinkers. Alcohol consumption also increased the risk (approx. 3-fold) in the cases with null genotype of GSTT1, though the association was not found to be significant when compared to non-drinkers. Our data have provided evidence that GST polymorphism modifies the susceptibility to HNSCC and have further demonstrated importance of gene-environment interaction in modulating the risk to HNSCC.

Genetic polymorphisms in cytochrome P4501B1 and susceptibility to head and neck cancer.

Cytochrome P4501B1 (CYP1B1), a polycyclic aromatic hydrocarbon (PAH) metabolizing CYP, is genetically polymorphic in humans and may be involved in the individual susceptibility to chemical-induced cancer. In the present study, genotype and haplotype frequencies of four single nucleotide polymorphisms (SNPs) in CYP1B1 that cause amino acid changes (Arg-Gly at codon 48, Ala-Ser at codon 119, Leu-Val at codon 432 and Asn-Ser at codon 453) were studied in 150 cases suffering from head and neck squamous cell carcinoma (HNSCC) and in an equal number of controls. A significant difference was observed for the distribution of variant genotypes of Arg48Gly (CYP1B1*2) and Ala119Ser (CYP1B1*2) polymorphisms of CYP1B1 in cases versus controls. No significant differences were observed for the distribution of variant genotypes-Leu432Val (CYP1B1*3) and Asn453Ser (CYP1B1*4), respectively. When the four SNPs were analyzed using a haplotype approach, SNPs at codon 48 (Arg48Gly) and codon 119 (Ala119Ser) exhibited complete linkage disequilibrium (LD) in all the cases and controls. Significant differences in the distribution of the two haplotypes (G-T-C-A and G-T-G-A) were observed both in the cases and in controls. Furthermore, our data indicates a several fold increase in risk in the cases who use tobacco (cigarette smoking or tobacco chewing) or alcohol with the variant genotypes of CYP1B1 (CYP1B1*2 and CYP1B1*3) suggesting the role of gene-environment interaction in the susceptibility to HNSCC.

Interaction of cytochrome P4501A1 genotypes with other risk factors and susceptibility to lung cancer.

Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. Since not much information is available regarding the polymorphism in drug metabolizing enzymes and lung cancer risk in the Indian population, the present case-control study attempted to investigate the association of polymorphisms in cytochrome P450 1A1 (CYP1A1) and glutathione-S-transferase M1 (GSTM1) with risk to squamous cell carcinoma of lung malignancy. Patients suffering from lung cancer (n=200) and visiting OPD facility of Department of Radiotherapy, King George's Medical University, Lucknow, were included in the study. Equal number (n=200) of age and sex matched healthy individuals were also enrolled in the study. Our data revealed that the variant genotypes of CYP1A1*2A, CYP1A1*2C and CYP1A1*4 were found to be over represented in the lung cancer patients when compared to controls. CYP1A1*2A variant genotypes (combined heterozygous and mutant genotypes) revealed significant association towards the lung cancer risk (OR: 1.93, 95%CI: 1.28-2.89, p=0.002). Likewise, GSTM1 null genotypes were found to be over represented in patients when compared to controls. Haplotype analysis revealed that CYP1A1 haplotype, C-G-C increased the lung cancer risk (OR: 3.90, 95%CI: 1.00-15.04, p=0.025) in the patients. The lung cancer risk was increased several two-to fourfold in the patients carrying the genotype combinations of CYP1A1*2A and GSTM1 suggesting the role of gene-gene interaction in lung cancer. Cigarette smoking or tobacco chewing or alcohol consumption was also found to interact with CYP1A1 genotypes in increasing the risk to lung cancer further demonstrating the role of gene-environment interaction in development of lung cancer.