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.

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.

The normal range of body mass index with high body fat percentage among male residents of Lucknow city in north India.

BACKGROUND & OBJECTIVES: Several studies have raised the suspicion that the body mass index (BMI) cut-off for overweight as defined by the WHO may not adequately reflect the actual overweight status. The present study looked at the relationship between BMI and body fat per cent (BF %) / health risks (hypertension and type 2 diabetes) in male residents of Lucknow city, north India to evaluate the validity of BMI cut-off points for overweight. METHODS: One thousand one hundred and eleven male volunteer subjects (18-69 yr) who participated in different programmes organized by the Institute during 2005 to 2008 were included in the study. BF% was measured using commercially available digital weight scale incorporating bioelectrical impedance (BI) analyzer. The proposed cut-off for BMI based on BF % was calculated using receiver operating characteristics (ROC) curve analysis. RESULTS: Forty four per cent subjects showed higher BF % (>25%) with BMI range (24-24.99 kg/m²). Sensitivity and specificity at BMI cut-off at 24.5 kg/m³ were 83.2 and 77.5, respectively. Sensitivity at BMI cut-off >25 kg/m² was reduced by 5 per cent and specificity increased by 4.6 per cent when compared to 24.5 cut-off. INTERPRETATION & CONCLUSIONS: The study subjects showed higher body fat percentage and risk factors like hypertension and type 2 diabetes at normal BMI range proposed by the WHO. The cut-off for BMI was proposed to be 24.5 kg/m² for our study population. If overweight is regarded as an excess of body fat and not as an excess of weight (increased BMI), the cut-off points for overweight based on BMI would need to be lowered. However, the confidence of estimate of the BMI cut-off in the present study may be considered with the limitations of BI analysis studies.

Seasonal trends of PM2.5 and PM10 in ambient air and their correlation in ambient air of Lucknow city, India.

The PM(10) concentration (µg/m(3)) in Lucknow city at 4 locations in three different seasons ranged between 148.6-210.8 (avg. 187.2 ± 17.1) during summer, 111.8-187.6 (avg. 155.7 ± 22.7) during monsoon and 199.3-308.8 (avg. 269.3 ± 42.9) during winter while PM(2.5) ranged between 32.4-67.2 (avg. 45.6 ± 10.9), 25.6-68.9 (avg. 39.8 ± 4.6) and 99.3-299.3 (avg. 212.4 ± 55.0) during respective seasons. The mass fraction ratio of PM(2.5) ranged between 0.22-0.92 (avg. 0.42 ± 0.26) and was significantly high during winter season indicating their composition.

'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.

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.

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.

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.

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.

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.

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.

Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis.

The association of polymorphism in cytochrome P450 2E1 (CYP2E1), the major microsomal ethanol metabolizing enzyme and its interaction with genes, involved in detoxification of reactive oxygen species, such as glutathione-S-transferases M1 (GSTM1) and alcohol intake, gamma-aminobutyric acid receptor gamma2 (GABRG2) was studied with the risk to alcoholic cirrhosis in a case-control study. A total of 160 alcoholic cirrhotic and 125 non-alcoholic cirrhotic cases, visiting the OPD facility of Gastroenterology Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGI), Lucknow, India and 250 non-alcoholic and 100 alcoholic controls having no evidence of liver disease were included in the study. PCR-based RFLP methodology was followed for genotyping studies. Our data revealed that the variant genotypes of CYP2E1 5B exhibited significant association with the alcoholic liver cirrhosis when compared to non-alcoholic controls (OR: 4.3; 95%CI: 1.5-12.4; p: 0.003) or non-alcoholic cirrhosis patients (OR: 5.4; 95%CI: 1.2-24.5; p: 0.01) or alcoholic controls (OR: 4.3; 95%CI: 0.95-19.62; p: 0.04). Haplotype approach revealed that haplotype T-A-T was found to be associated with more than 5-fold increase in risk for alcoholic cirrhosis. Likewise, combination of variant genotype of CYP2E1 5B with null genotype of GSTM1, a phase II detoxification enzyme, resulted in several fold increase in risk in alcoholic cirrhotic patients when compared with non-alcoholic controls or non-alcoholic cirrhotic patients. Further, the combination of variant genotype of CYP2E1 5B with GABRG2, significantly increased the risk upto 6.5-fold in alcoholic cirrhotic patients when compared with non-alcoholic controls thereby suggesting the role of gene-gene interaction in alcoholic cirrhosis.

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.

Induction of hsp70, alterations in oxidative stress markers and apoptosis against dichlorvos exposure in transgenic Drosophila melanogaster: modulation by reactive oxygen species.

We examined a hypothesis that reactive oxygen species (ROS) generated by organophosphate compound dichlorvos modulates Hsp70 expression and anti-oxidant defense enzymes and acts as a signaling molecule for apoptosis in the exposed organism. Dichlorvos (0.015-15.0 ppb) without or with inhibitors of Hsp70, superoxide dismutase (SOD) and catalase (CAT) were fed to the third instar larvae of Drosophila melanogaster transgenic for hsp70 (hsp70-lacZ) Bg(9) to examine Hsp70 expression, oxidative stress and apoptotic markers. A concentration- and time-dependent significant increase in ROS generation accompanied by a significant upregulation of Hsp70 preceded changes in antioxidant defense enzyme activities and contents of glutathione, malondialdehyde and protein carbonyl in the treated organisms. An inhibitory effect on SOD and CAT activities significantly upregulated ROS generation and Hsp70 expression in the exposed organism while inhibition of Hsp70 significantly affected oxidative stress markers induced by the test chemical. A comparison made among ROS generation, Hsp70 expression and apoptotic markers showed that ROS generation is positively correlated with Hsp70 expression and apoptotic cell death end points indicating involvement of ROS in the overall adversity caused by the test chemical to the organism. The study suggests that (a) Hsp70 and anti-oxidant enzymes work together for cellular defense against xenobiotic hazard in D. melanogaster and (b) free radicals may modulate Hsp70 expression and apoptosis in the exposed organism.

Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women.

PURPOSE: Single nucleotide polymorphism (SNP) at position -309 (T309G) in MDM-2 promoter induces tumor formation in the individuals possessing inherited p53 mutations. The present study was undertaken to investigate the association of MDM-2 SNP309, p53 Arg72Pro, and p53 intron-6 G/A polymorphism with total, premenopausal, and postmenopausal breast cancer risks in Indian women. METHODS: Genotyping of MDM-2 SNP309, p53 Arg72Pro, and p53 intron-6 G/A in 104 patients and 105 controls was performed either by ARMS-PCR or by polymerase chain reaction and direct sequencing. RESULTS: The p53 Arg72Pro heterozygous variant and in combination with its homozygous variant exhibited a significant protective association with total (odds ratio [95% confidence interval]: 0.42 [0.22-0.81] and 0.46 [0.25-0.85], p value; 0.007 and 0.012) and postmenopausal breast cancer risk (odds ratio [95% confidence interval]: 0.25 [0.07-0.73] and 0.27 [0.08-0.77], p value; 0.009 and 0.013]. Neither combined nor homozygous/heterozygous MDM-2 SNP309G was associated with total, premenopausal, or postmenopausal breast cancer risk; however, MDM-2 SNP309G, along with p53 Arg72Pro heterozygous variant, showed a significant protective association with premenopausal breast cancer risk (odds ratio [95% confidence interval]: 0.18 [0.02-1.20], p value; 0.041 for homozygous + heterozygous MDM-2 SNP309G). CONCLUSIONS: The results indicate protective associations of p53 Arg72Pro heterozygous variant with postmenopausal and MDM-2 SNP309G along with p53 Arg72Pro heterozygous variant with premenopausal breast cancer risk.

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.

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.

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.