34 results on '"Mittal, Balraj"'
Search Results
2. Potential role of GABA A receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population
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Kumari, Ritu, Lakhan, Ram, Kalita, J., Garg, R.K., Misra, U.K., and Mittal, Balraj
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- 2011
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3. A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke
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Kalita, Jayantee, Somarajan, Bindu I., Kumar, Bishwanath, Mittal, Balraj, and Misra, Usha K.
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- 2011
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4. Genetic association of interleukin-1β (− 511C/T) and interleukin-1 receptor antagonist (86 bp repeat) polymorphisms with Type 2 diabetes mellitus in North Indians
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Achyut, B.R, Srivastava, Akanksha, Bhattacharya, Sandeep, and Mittal, Balraj
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- 2007
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5. Association of Genetic Polymorphism of Glutathione S-transferase M1, T1, P1 and Susceptibility to Bladder Cancer
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Srivastava, Daya Shankar Lal, Mishra, Dhruva Kumar, Mandhani, Anil, Mittal, Balraj, Kumar, Anant, and Mittal, Rama Devi
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- 2005
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6. CYP7A1 (−204 A>C; rs3808607 and −469 T>C; rs3824260) promoter polymorphisms and risk of gallbladder cancer in North Indian population.
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Srivastava, Anvesha, Choudhuri, Gourdas, and Mittal, Balraj
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CHOLESTEROL hydroxylase ,GENETIC polymorphisms ,GALLSTONES ,CANCER risk factors ,GALLBLADDER cancer ,POLYMERASE chain reaction ,DISEASE susceptibility ,DISEASES ,INDIANS (Asians) - Abstract
Abstract: Cholesterol 7-α hydroxylase (CYP7A1), which is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis, may affect cholesterol homeostasis and result in gallstone formation that is a major risk factor for gallbladder cancer (GBC) pathogenesis. Genetic variations in CYP7A1 may influence its expression and thus may affect the risk of gallstone disease and GBC. We aimed to study the association of 2 promoter polymorphisms of CYP7A1 (−204 A>C [rs3808607] and −469 T>C [rs3824260]) in gallstone and GBC susceptibility in North Indian population. The study included 185 GBC patients, 195 symptomatic gallstone patients, and 200 healthy controls. Genotyping for both polymorphisms was done by polymerase chain reaction–restriction fragment length polymorphism method. Although the CC genotype of CYP7A1 −204 A>C was not significantly associated with gallstone disease (P = .083, odds ratio [OR] = 1.69, 95% confidence interval [CI] = 0.9-3.0), it was conferring higher risk for GBC (P = .018, OR = 2.05, 95% CI = 1.1-3.7). However, CYP7A1 −469 T>C was not associated with gallstone disease and GBC risk in our population. After subgroup stratifications on the basis of sex and gallstone status, CC genotype and variant allele of CYP7A1 −204 A>C imparted higher risk for GBC in women (P = .003, OR = 3.30, 95% CI = 1.5-7.2) and patients without gallstones (P = .045, OR = 1.91, 95% CI = 1.2-3.6). Haplotype analysis of the 2 polymorphisms showed that C,T (P = .045, OR = 1.84, 95% CI = 1.0-3.3) and C,C (P = .0001, OR = 3.10, 95% CI = 1.6-6.0) haplotypes had elevated risk of GBC predisposition. CYP7A1 −469 T>C is not associated with gallstone disease or GBC risk. Although CYP7A1 −204 A>C might play a modest role in gallstone susceptibility, it is an independent risk factor for GBC in North Indian population. Underlying mechanism for GBC susceptibility by CYP7A1 (−204 A>C and −469 T>C) haplotype appears to be independent of gallstone pathway and is believed to involve genotoxicity resulting from subnormal bile acid production. [Copyright &y& Elsevier]
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- 2010
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7. Association of alpha subunit of GABAA receptor subtype gene polymorphisms with epilepsy susceptibility and drug resistance in north Indian population.
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Kumari, Ritu, Lakhan, Ram, Kalita, J., Misra, U.K., and Mittal, Balraj
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Abstract: GABA (γ-amino butyric acid) receptors have always been an inviting target in the etiology and treatment of epilepsy because of its role as a major inhibitory neurotransmitter in the brain. The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11+15 A>G (rs2279020) and GABRG2 588C>T (rs211037) genes in seizure susceptibility and pharmaco-resistance in northern Indian patients with epilepsy. A total of 395 epilepsy patients and 199 control subjects were enrolled for present study. The genotyping was done by PCR-RFLP methods. The GABRA1 IVS11+15 A>G polymorphism conferred high risk for epilepsy susceptibility at genotype ‘AG’ (P =0.004, OR=1.77, 95% CI=1.20–2.63), ‘GG’ (P =0.01, OR=1.80, 95% CI=1.15–2.80) and G allele level (P =0.001, OR=1.50, 95% CI=1.16–1.92). Moreover this polymorphism was also associated with multiple drug resistance in patients with epilepsy for homozygous variant ‘GG’ genotype (P =0.031, OR=1.84, 95% CI=1.05–3.23) and G allele (P =0.020, OR=1.43, 95% CI=1.05–1.95). However GABRG2 588C>T polymorphism was not found to be associated either with epilepsy susceptibility or with drug resistance. Overall results indicate differential role of different subunits of GABA
A receptor subtypes in epilepsy susceptibility and pharmacotherapy. [Copyright &y& Elsevier]- Published
- 2010
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8. Association between allelic variation due to short tandem repeats in tRNA gene of Entamoeba histolytica and clinical phenotypes of amoebiasis.
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Jaiswal, Virendra, Ghoshal, Ujjala, Mittal, Balraj, Dhole, Tapan N., and Ghoshal, Uday C.
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ALLELES , *ENTAMOEBA histolytica , *PHENOTYPES , *AMEBIASIS , *TANDEM repeats , *TRANSFER RNA , *LOCUS (Genetics) - Abstract
Highlights: [•] 9 alleles were found in DA, 8 in AL, 4 in NK2, 5 in RR, 10 in SD and 7 in SQ loci. [•] Locus DA, AL, SQ and STGAD exhibited more variations as compared to other loci. [•] Association was found b/w allelic variants and clinical phenotypes of amoebiasis. [•] Study reveals association b/w allelic variation and clinical outcome of amoebiasis. [ABSTRACT FROM AUTHOR]
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- 2014
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9. Influence of IL-1β, STAT3 & 5 and TLR-5 gene polymorphisms on rheumatic heart disease susceptibility in north Indian population.
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Bhatt, Mansi, Kumar, Surendra, Garg, Naveen, Siddiqui, Mohammad Haris, and Mittal, Balraj
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RHEUMATIC heart disease , *DISEASE susceptibility , *HEART valves , *MITRAL valve , *GENES , *POPULATION - Abstract
Rheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Many studies have demonstrated the contribution of host genetic factors in susceptibility to RHD and many cytokine gene variants have been linked with susceptibility to RHD. We sought to determine the role of genetic variants in IL-1β, STAT3, STAT5B and TLR5 genes in conferring risk of RHD in two cohorts of RHD patients. The study included 400 echocardiography confirmed RHD patients and 300 controls from North Indian Population. We categorized RHD patients into two sub-groups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping for all the polymorphisms was done using TaqMan /PCR-RFLP methods. Our results showed that the genotypic frequencies of IL-1β, STAT3, STAT5B andTLR5 genes polymorphisms were significantly associated with RHD risk. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings with RHD risk. In subgroup analysis, STAT3 polymorphism remained significant with MVL in RHD patients. IL-1β, STAT3, STAT5B and TLR5 genes polymorphism may be useful markers for the identification of individuals with high risk of RHD in the susceptible population. • IL-1β, STAT3, TLR5 gene polymorphism affect risk of rheumatic heart disease (RHD). • STAT3 variant associates with higher risk of mitral-valve disease in RHD patients. • These genetic variants may be useful biomarkers for RHD in susceptible population. [ABSTRACT FROM AUTHOR]
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- 2019
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10. Genetic landscape of gallbladder cancer: Global overview.
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Mehrotra, Ravi, Tulsyan, Sonam, Hussain, Showket, Mittal, Balraj, Singh Saluja, Sundeep, Singh, Sandeep, Tanwar, Pranay, Khan, Asiya, Javle, Milind, Hassan, Manal M., Pant, Shubham, De Aretxabala, Xabier, Sirohi, Bhawna, Rajaraman, Preetha, Kaur, Tanvir, and Rath, G.K.
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CANCER genetics , *GALLBLADDER cancer , *CANCER diagnosis , *GENETIC polymorphisms , *DISEASE susceptibility - Abstract
Abstract Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC), characterized by late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. So, diverse epidemiology along with etiological factors have been discussed in the current article. Present review unravels the germ line polymorphisms contributing to GBC susceptibility through candidate gene approach and GWAS. GBC is enriched with multiple mutations consisting of both passenger and driver mutations. The identification of the hotspot driver mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. Thus, this review sheds lights on both traditional low throughput methods along with high throughput NGS used to determine somatic mutations in cancer. With the advent of GWAS and high throughput sequencing methods, it is possible to comprehend the mutational landscape of this enigmatic disease. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, management of tumor heterogeneity as a therapeutic challenge has been discussed. Future goals involve liquid biopsy based research for better clinical management of the disease. Therefore, research efforts involving discovery of non- invasive markers for early stage cancer detection along with novel therapies should be directed. [ABSTRACT FROM AUTHOR]
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- 2018
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11. Influence of cytokine gene polymorphism on the risk of rheumatic heart disease – A meta-analysis.
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Bhatt, Mansi, Kumar, Surendra, Siddiqui, Mohammad Haris, Garg, Naveen, and Mittal, Balraj
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GENETIC polymorphisms , *POPULATION genetics , *CHROMOSOME polymorphism , *INTERLEUKINS , *RHEUMATIC heart disease - Abstract
RHD is an inflammatory disease resulting from interactive immune, genetic, and environmental factors. Various, epidemiological studies have shown the association of genetic variants of cytokine genes with a predisposition to RHD. However, the results from different populations are inconsistent. Therefore, we carried out a meta- analysis of twenty-three published case-control studies and the results indicated that TGF-β1 +869 T/C (T vs. C: OR = 7.68, 95% CI = 1.62–36.50; TT + CT vs. CC OR = 1.83, 95%CI = 1.39–2.41), TGF-β1-509 (T vs. C: OR = 2.76, 95% CI = 1.33–5.75), TNF-α(AA vs. GG: OR = 4.93,95% CI = 2.83–8.58; A vs. G: OR = 2.15, 95% CI = 1.13–4.12) and IL-1β −511C/T (CC + CT vs. TT: OR = 1.35, 95%CI = 1.02–1.78; C vs. T: OR = 2.36, 95% CI = 1.66–3.37) were significantly associated with increased risk of RHD. On the other hand, IL-10(−1082)G/A polymorphism (GA vs. AA: OR = 0.91, 95% CI = 0.36–2.33; G vs. A: OR = 1.90, 95% CI = 0.58–6.22) and IL-6–174 G/C (CC + GC vs. GG: OR = 0.68, 95%CI = 0.32–1, C vs. G: OR = 1.14, 95% CI = 0.82–1.60) were not associated with modified RHD risk. The meta-analysis results were similar in Asians and non-Asians. Therefore, cytokine gene polymorphisms play important role in the genetic susceptibility of RHD in rheumatic fever patients. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.
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Mhatre, Sharayu, Wang, Zhaoming, Nagrani, Rajini, Badwe, Rajendra, Chiplunkar, Shubhada, Mittal, Balraj, Yadav, Saurabh, Zhang, Haoyu, Chung, Charles C, Patil, Prachi, Chanock, Stephen, Dikshit, Rajesh, Chatterjee, Nilanjan, and Rajaraman, Preetha
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GALLBLADDER cancer , *CARCINOGENS , *GENETIC polymorphisms , *NUCLEOTIDE sequence , *GENE expression , *ALLELES , *COMPARATIVE studies , *DISEASE susceptibility , *GALLBLADDER tumors , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *META-analysis , *PROGNOSIS , *RESEARCH , *TUMOR classification , *EVALUATION research , *CASE-control method , *SEQUENCE analysis , *GENOTYPES - Abstract
Background: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer.Methods: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20-80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20-80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association.Findings: The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8 × 10-9; replication p=0·01; combined p=2·3 × 10-10); rs17209837 (GWAS p=2·0 × 10-8; replication p=0·02; combined p=2·3 × 10-9), and rs4148808 (GWAS p=2·4 × 10-8; replication p=0·008; combined p=2·7 × 10-9). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30-1·66; p=2·31 × 10-10) for rs1558375, 1·61 (1·38-1·89; p=2·26 × 10-9) for rs17209837, and 1·57 (1·35-1·82; p=2·71 × 10-9) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 [95% CI 1·80-5·49]).Interpretation: To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4, underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer.Funding: The Tata Memorial Centre and Department of Biotechnology. [ABSTRACT FROM AUTHOR]- Published
- 2017
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13. Association study of inflammatory genes with rheumatic heart disease in North Indian population: A multi-analytical approach.
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Gupta, Usha, Mir, Snober S., Garg, Naveen, Agarwal, Surendra K., Pande, Shantanu, and Mittal, Balraj
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RHEUMATIC heart disease , *STREPTOCOCCAL diseases , *GENOTYPES , *PATHOGENIC microorganisms , *DISEASE susceptibility - Abstract
Rheumatic heart disease (RHD) is an inflammatory, autoimmune disease; occurring as a consequence of group A streptococcal infection complicated by rheumatic fever (RF). An inappropriate immune response is the central signature tune to the complex pathogenesis of RHD. However, some of those infected develop RHD, and genetic host susceptibility factors are thought to play a key role in diseasedevelopment. Therefore, the present study was designed to explore the role of genetic variants in inflammatory genes in conferring risk of RHD. The study recruited total of 700 subjects, including 400 RHD patients and 300 healthy controls. We examined the associations of 8 selected polymorphisms in seven inflammatory genes: IL-6 [rs1800795 G/C], IL-10 [rs1800896 G/A], TNF-A [rs1800629 G/A], IL-1β [rs2853550C/T], IL-1 VNTR [rs2234663], TGF-β1 [rs1800469C/T]; [rs1982073 T/C], and CTLA-4 [rs5742909C/T] with RHD risk. Genotyping for all the polymorphisms was done using PCR-ARMS/PCR/RFLP methods. Multifactor dimensionality reduction and classification and regression tree approaches were combined with logistic regression to discover high-order gene-gene interactions in studiedgenes involved in RHD susceptibility.In univariate logistic regression analysis, we found significant association of variant-containing genotypes (CT&TT) of TGF-β1 869 T/C [rs1982073]; [p = 0.0.004 & 0.001, OR (95% CI) = 1.65 (1.2–2.3) & 2.25 (1.4–3.6) respectively], variant genotype (CC) of IL-1β −511C/T [rs2853550]; [p = 0.001, OR (95% CI) = 2.33 (1.4–3.8)] and IL-1 VNTR [rs2234663]; [p = 0.03, OR (95% CI) = 5.25 (1.2–23.4)] SNPs with RHD risk. CART analysis revealed that individuals with the combined genotypes of TGF-β1 T/C_ rs1982073 (CT/TT) and IL-1 β_ rs2853550 (CC) had significantly higher susceptibility for RHD [p = 0.0005, OR (95% CI) = 5.91 (2.9–12.5)]. In MDR analysis, TGF-β1 869T > C yielded the highest testing accuracy of 0.562. In conclusion, using multi-analytical approaches, our study revealed important role of TGF-β1 869 T/C [rs1982073] in RHD susceptibility. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Signal transducers and activators of transcription (STATs) gene polymorphisms related with susceptibility to rheumatic heart disease in north Indian population.
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Gupta, Usha, Mir, Snober S., Srivastava, Apurva, Garg, Naveen, Agarwal, Surendra K., Pande, Shantanu, and Mittal, Balraj
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STAT proteins , *GENETIC polymorphisms , *RHEUMATIC heart disease , *INFLAMMATION , *HEART valves , *CYTOKINES , *INDIGENOUS peoples of the Americas , *DISEASES - Abstract
Rheumatic heart disease (RHD) is the most serious complication of heart that comprises inflammatory reactions in heart valves. Cytokines play a critical role in triggering inflammatory reactions and they activate the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signaling pathway. Altered signals of STATs play important roles in the balance between proinflammatory and anti-inflammatory cytokines in inflammatory diseases. The aim of the present study was to investigate for the association of polymorphisms related with STAT genes, i.e. STAT3 (rs4796793 C/G) and STAT5b (rs6503691 C/T) with the pathogenesis of RHD. This case-control association study involved 300 healthy controls and 400 RHD patients from North Indian Population. We categorized RHD patients into two subgroups based on involvement of heart valves, mitral valve lesion alone (MVL), and combined valve lesions including mitral valve (CVL). Genotyping was done by RFLP/Taqman probes. We observed that STAT3 CG and GG genotypes were significantly associated with RHD (p = 0.030 and p = 0.014 respectively), STAT5b CT and TT genotypes were also significantly associated with RHD (p = 0.001). Haplotype analysis revealed that minor alleles of both the variants (Grs4796793Trs6503691) were significantly associated (p < 0.0001) with increased risk of the disease susceptibility irrespective of gender or age of onset of the disease. However, the polymorphisms were not involved in severity of RHD as both MVL and CVL patients were equally affected. STAT Grs4796793Trs6503691 carriers may have reduced production of STAT3 leading to damage of heart valves. Thus, STAT genes polymorphisms may be useful markers for the identification of individuals with high risk of RHD in the susceptible population. [ABSTRACT FROM AUTHOR]
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- 2014
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15. Genetic predisposition to left ventricular dysfunction: a multigenic and multi-analytical approach.
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Mishra, Avshesh, Srivastava, Anshika, Mittal, Tulika, Garg, Naveen, and Mittal, Balraj
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DISEASE susceptibility , *LEFT heart ventricle diseases , *SINGLE nucleotide polymorphisms , *CONGESTIVE heart failure , *ANGIOTENSIN II - Abstract
Background Left ventricular dysfunction (LVD) is a complex, multifactorial condition, caused by mechanical, neurohormonal, and genetic factors. We have previously observed association of renin–angiotensin–aldosterone system (RAAS), matrix metalloproteinases (MMPs) and inflammatory pathway genes with LVD. Therefore the present study was undertaken to identify the combination of genetic variants and their possible interactions contributing towards genetic susceptibility to LVD in the background of coronary artery disease (CAD). Methods and results The study included 230 healthy controls and 510 consecutive patients with angiographically confirmed CAD. Among them, 162 with reduced left ventricle ejection fraction (LVEF ≤ 45%) were categorized as having LVD. We analyzed 11 polymorphisms of RAAS, MMPs and inflammatory pathways. Single locus analysis showed that AT1 A1166C (p value < 0.001; OR = 3.67), MMP9 R668Q (p value = 0.007; OR = 3.48) and NFKB1-94 ATTG ins/del (p value = 0.013; OR = 2.01) polymorphisms were independently associated with LVD when compared with both non-LVD patients and healthy controls. High-order gene–gene interaction analysis, using classification and regression tree (CART) and multifactor dimensionality reduction (MDR) revealed that AT1 A1166C and NFKB1 -94 ATTG ins/del polymorphisms jointly increased the risk of LVD to great extent (p-value = 0.001; OR = 8.55) and best four-factor interaction model consisted of AT1 A1166C, MMP7 A-181G, MMP9 R668Q and NFKB1 -94 ATTG ins/del polymorphisms with testing accuracy of 0.566 and cross validation consistency (CVC) = 9/10 (permutation p < 0.001) showed increased risk for LVD respectively. Conclusion AT1 A1166C independently and in combination with MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms plays important role in conferring genetic susceptibility to LVD in CAD patients. [ABSTRACT FROM AUTHOR]
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- 2014
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16. Significant role of CYP450 genetic variants in cyclophosphamide based breast cancer treatment outcomes: a multi-analytical strategy.
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Tulsyan, Sonam, Agarwal, Gaurav, Lal, Punita, and Mittal, Balraj
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CYCLOPHOSPHAMIDE , *BREAST cancer , *SINGLE nucleotide polymorphisms , *CYTOCHROME P-450 , *HEALTH outcome assessment - Abstract
Abstract: Background: Cyclophosphamide (CP), an alkylating chemotherapeutic drug, is catalyzed by the Phase I cytochrome P450 (CYPs) isozymes — CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19. Hence this study aimed to elucidate the influence of genetic variants in CYP450 metabolizing enzymes on breast cancer treatment outcomes, using multi-analytical approaches. Methods: Treatment response was noticed in 111 patients whereas 234 patients were followed for myelo-toxicity. Eight known functional single nucleotide polymorphisms (SNPs) in six CYP450 genes were selected for the study on the basis of CP metabolizing enzyme polymorphisms. The possible functional effects of CYP450 polymorphisms were determined by online Web servers F-SNP. Multifactor dimensionality reductions (MDR), haplotype analysis were combined with logistic regression to characterize gene–gene interaction model with treatment outcomes. Results: Haplotype analysis revealed significant association of Grs10509681-*1rs1799853-*3rs1057910-Grs4244285 on chromosome 10 with overall toxicity (P=0.024) and grade 2–4 leucopenia (P=0.03). On MDR analysis, CYP3A5*3, CYP2C19*2, CYP2B6*5 yielded the highest testing accuracy for treatment response (0.60) and CYP2C8*3, CYP2C9*2 for overall toxicity (0.50). Conclusion: Multi-analytical approaches may provide a better clinical prediction of pharmacogenetic based treatment outcomes in breast cancer patients. [Copyright &y& Elsevier]
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- 2014
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17. Assessment of clinical outcomes in breast cancer patients treated with taxanes: multi-analytical approach.
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Tulsyan, Sonam, Chaturvedi, Pankaj, Singh, Abhishek Kumar, Agarwal, Gaurav, Lal, Punita, Agrawal, Sushma, Mittal, Rama Devi, and Mittal, Balraj
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BREAST cancer treatment , *TAXANES , *GENETIC polymorphisms , *CANCER chemotherapy , *ADJUVANT treatment of cancer , *HEALTH outcome assessment - Abstract
Abstract: Polymorphisms in genes encoding CYPs (Phase I) and ABCB1 (Phase III) enzymes may attribute to variability of efficacy of taxanes. The present study aims to find the influence of CYP and ABCB1 gene polymorphisms on taxanes based clinical outcomes. 132 breast cancer patients treated with taxanes based chemotherapy were genotyped for CYP3A4*1B, CYP3A5*3, CYP1B1*3, CYP2C8*3, ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms using PCR-RFLP. Associations of genetic variants with clinical outcomes in terms of response in 58 patients receiving neo-adjuvant chemotherapy (NACT), and chemo-toxicity in 132 patients were studied. Multifactor dimensionality reduction (MDR) analysis was performed to evaluate higher order gene–gene interactions with clinical outcomes. Pathological response to taxane based NACT was associated with GA genotype as well as A allele of CYP3A5*3 polymorphism (Pcorr =0.0465, Pcorr =0.0465). Similarly, association was found in dominant model of CYP3A5*3 polymorphism with responders (Pcorr =0.0465). Haplotype analysis further revealed A CYP3A4 –A CYP3A5 haplotype to be significantly associated with responders (Pcorr =0.048). In assessing toxicity, significant association of variant (TT) genotype and T allele of ABCB1 2677G>T/A polymorphism, was found with ‘grade 1 or no leucopenia’ (Pcorr =0.0465, Pcorr =0.048). On evaluating higher order gene–gene interaction models by MDR analysis, CYP3A5*3; ABCB11236C>T and ABCB1 2677G>T/A; ABCB1 3435C>T and CYP1B1*3 showed significant association with treatment response, grade 2–4 anemia and dose delay/reduction due to neutropenia (P=0.024, P=0.004, P=0.026), respectively. Multi-analytical approaches may provide a better assessment of pharmacogenetic based treatment outcomes in breast cancer patients treated with taxanes. [Copyright &y& Elsevier]
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- 2014
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18. PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females.
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Rai, Rajani, Sharma, Kiran L., Misra, Sanjeev, Kumar, Ashok, and Mittal, Balraj
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GALLBLADDER cancer , *CANCER in women , *STEM cells , *PROSTATE-specific antigen , *ONCOGENES , *MEDICAL care , *LINKAGE disequilibrium , *HAPLOTYPES - Abstract
Abstract: Background and aim: PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population. Methodology: A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case–control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons. Results: No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25). Conclusions: These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner. [Copyright &y& Elsevier]
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- 2013
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19. SCN1AIVS5-91G>A polymorphism is associated with susceptibility to epilepsy but not with drug responsiveness.
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Kumari, Ritu, Lakhan, Ram, Kumar, Surendra, Garg, R.K., Misra, U.K., Kalita, J., and Mittal, Balraj
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GENETIC polymorphisms , *GENETICS of disease susceptibility , *GENETICS of epilepsy , *SODIUM channels , *ALLELES , *CARBAMAZEPINE - Abstract
Sodium channel alpha subunit type 1 (SCN1A) is voltage gated ion channel which plays critical role in membrane excitability. A common SCN1A IVS5-91G>A (rs3812718) allele has been attributed to be a possible modifying factor for epilepsy susceptibility and therapeutic response. In the present study, we enrolled 485 epilepsy patients and 298 age-sex matched controls free of neurological deficits. Therapeutic response of carbamazepine/oxcarbamazepine (CBZ/OXC) and other antiepileptic drugs were observed in terms of drug responsiveness and drug resistance. Genotyping of SCN1A IVS5-91G>A is done by Taqman custom designed assay; in a real time7500HT System. We observe highly significant association [(P-values for GA (P = 6.58 × 10−5, OR = 2.13, 95% CI = 1.47–3.09) and AA (P = 4.11 × 10−9, OR = 3.59, 95% CI = 2.35–5.50)] at variant genotypes as well as A allele (P = 6.92 × 10−11), OR = 1.99, 95%, CI = 1.62–2.45) in epilepsy patients versus control subjects. The relative risk for epilepsy susceptibility due to variant containing genotypes (GA + AA) was also significant (P = 1.64 × 10−5; OR = 2.56; 95% CI = 1.80–3.65) when compared with homozygous wild-type GG. The risk in recessive model (P = 1.34 × 10−5; OR = 2.12; 95% CI = 1.51–2.97) was also apparent when compared with GA + GG. In case-only analysis, we evaluated the effect of SCN1A IVS5-91G>A polymorphism with drug resistance of anti-epileptic drug therapies. However, we did not observe significant associations either with patients showing drug resistance to CBZ/OXC monotherapy or polytherapy. In conclusion, we report that SCN1AIVS5-91G>A polymorphism is associated with epilepsy susceptibility but not with drug responsiveness in epilepsy patients from North India. [ABSTRACT FROM AUTHOR]
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- 2013
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20. DCC (deleted in colorectal carcinoma) gene variants confer increased susceptibility to gallbladder cancer (Ref. No.: Gene-D-12-01446)
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Rai, Rajani, Sharma, Kiran L., Tiwari, Swati, Misra, Sanjeev, Kumar, Ashok, and Mittal, Balraj
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DELETION mutation , *GENETIC polymorphisms , *GENETICS of colon cancer , *DISEASE susceptibility , *GALLBLADDER cancer , *TUMOR suppressor genes - Abstract
Abstract: Background and aim: GBC is a lethal and multifaceted disease. Deleted in colorectal carcinoma (DCC) is a well known tumor suppressor gene. Recently a small genome-wide association study (GWAS) identified DCC to be significantly associated with gallbladder cancer (GBC) susceptibility in a Japanese population sample. However, the study sample size was small and lacked independent replication. Therefore, the present study was carried out to replicate the association of two GWAS identified DCC SNPs (A>Grs4078288, C>Trs7504990) and two other SNPs (C>Grs2229080 and A>Grs714) previously associated with various cancers. Methodology: The study was accomplished in 406 GBC cases and 260 healthy control samples from North India. Genotyping was carried out by PCR-RFLP and Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16 and functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP). Result: We did not observe association with GWAS-identified SNPs of DCC but other SNPs showed significant association. In addition, a DCC haplotype Grs2229080-Ars4078288-Crs7504990-Ars714 conferred high risk of GBC in India. The haplotype associated risk was independent of gallstone, sex or tobacco usages which are well-known modifiers of GBC risk. Further analysis suggested DCC A>Grs714 as a major risk conferring SNP in the Indian population. Conclusion: This study re-affirms the role of plausible tumor suppressor DCC variants, in gallbladder carcinogenesis and the risk haplotype may be explored as a useful marker for GBC susceptibility. [Copyright &y& Elsevier]
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- 2013
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21. Candidate gene studies in gallbladder cancer: A systematic review and meta-analysis
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Srivastava, Kshitij, Srivastava, Anvesha, Sharma, Kiran Lata, and Mittal, Balraj
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GALLBLADDER cancer , *DISEASE incidence , *SYSTEMATIC reviews , *META-analysis , *EPIDEMIOLOGY of cancer , *CANCER genetics , *GENETICS of disease susceptibility , *GENETIC polymorphisms - Abstract
Abstract: Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene–disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analyzed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with >3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility except TP53 (rs1042522) polymorphism. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene–gene, gene–environment interactions and high-risk haplotypes. [Copyright &y& Elsevier]
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- 2011
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22. Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population
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Kumari, Ritu, Lakhan, Ram, Kalita, J., Garg, R.K., Misra, U.K., and Mittal, Balraj
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GENETIC polymorphisms , *EPILEPSY , *DISEASE susceptibility , *DRUG therapy , *DRUG resistance , *ANTICONVULSANTS - Abstract
Abstract: Background: GABAA receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also. Methods: We investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABAA receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods. Results: The GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P=0.018), CC (P=0.0001) genotype and for C allele (P=0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P=0.012), TT (P=0.778) genotype and for variant T allele (P=0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism. Conclusion: Overall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABAA receptor in epilepsy susceptibility in north Indian population. [Copyright &y& Elsevier]
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- 2011
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23. Role of mitochondrial DNA 4977-bp deletions in esophageal cancer susceptibility and prognosis in a northern Indian population
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Upadhyay, Rohit, Jain, Meenu, Kumar, Shaleen, ChandGhoshal, Uday, and Mittal, Balraj
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MITOCHONDRIAL DNA , *ESOPHAGEAL cancer , *DISEASE susceptibility , *POLYMERASE chain reaction , *CANCER invasiveness , *PROGNOSIS ,CANCER histopathology - Abstract
Abstract: The mitochondrial DNA 4977-bp deletion (▵mtDNA4977) has been explored in various cancers, but its predictive or prognostic role in esophageal cancer is poorly understood. The objective of the present study was to investigate a possible role of ▵mtDNA4977 in susceptibility and prognosis of esophageal cancer in a northern Indian population. The study was performed in 39 histopathologically confirmed cases with esophageal cancer. Tumor, normal tissues, and intravenous blood samples were taken for detection of ▵mtDNA4977 through a duplex polymerase chain reaction technique. ▵mtDNA4977 was detected in two tumors and one adjacent normal tissue sample, but in none of the blood samples. All three patients with ▵mtDNA4977 were male, with squamous cell carcinoma in the middle third of the esophagus. Survival analysis suggested a role of ▵mtDNA4977 in prognosis of esophageal cancer patients. Despite the low frequency of ▵mtDNA4977 in esophageal cancer patients of northern India, this feature may have a role in esophageal cancer progression and prediction of survival outcome. [Copyright &y& Elsevier]
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- 2009
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24. Association of NAT2 Gene Polymorphisms with Susceptibility to Esophageal and Gastric Cancers in the Kashmir Valley
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Malik, Manzoor Ahmad, Upadhyay, Rohit, Modi, Dinesh Raj, Zargar, Showket Ali, and Mittal, Balraj
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GENETIC polymorphisms , *GENETICS of disease susceptibility , *STOMACH cancer , *ESOPHAGEAL cancer , *ACETYLTRANSFERASES , *CARCINOGENS , *GENETICS ,CANCER susceptibility - Abstract
Background and Aims: The high incidence of gastrointestinal cancers in the Kashmir Valley has been attributed to the presence of many chemical carcinogens such as nitrosamines and heterocyclic amines in tobacco and salted tea. Due to functional polymorphisms of the N-acetyltransferase 2 (NAT2) gene, there may be interindividual differences in the metabolism of heterocyclic amines. We undertook this study to determine the influence of NAT2 gene polymorphisms (rs1799929, rs1799930, rs1799931) as well as their interactions with environmental carcinogens on the modulation of risk of esophageal and gastric cancers (EC and GC) in the Kashmir Valley. Methods: A case/control study was performed involving 398 study subjects (182 controls, 123 EC and 93 GC). DNA samples were genotyped by PCR-RFLP method. Results: None of the three NAT2 polymorphic alleles was found to be independently associated with risk of EC/GC but haplotypes C481A590G857 and T481A590G857 significantly modulated the risk of EC and GC, respectively (OR=0.56; 95% CI=0.34–0.91; p =0.018 and OR=4.61; 95% CI=1.90–11.17; p =0.001). NAT2 slow acetylator genotypes (NAT2∗5, NAT2∗6, NAT2∗7) significantly increased the risk of esophageal squamous cell carcinoma (ESCC, OR=1.73; 95% CI=1.01–2.97; p =0.047). Smoking and salted tea consumption were independent risk factors, but they did not show any interaction with NAT2 slow acetylator genotypes. Conclusions: NAT2 slow acetylator genotype may increase susceptibility to ESCC, and NAT2 haplotypes (C481A590G857 and T481A590G857) may predict susceptibility to EC and GC in the Kashmir Valley. [Copyright &y& Elsevier]
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- 2009
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25. Functional polymorphisms of cyclooxygenase-2 (COX-2) gene and risk for esophageal squmaous cell carcinoma
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Upadhyay, Rohit, Jain, Meenu, Kumar, Shaleen, Ghoshal, Uday Chand, and Mittal, Balraj
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GENETIC polymorphisms , *CYCLOOXYGENASE 2 , *SQUAMOUS cell carcinoma , *ESOPHAGEAL cancer , *NEOVASCULARIZATION , *APOPTOSIS , *CYTOKINES , *GENOTYPE-environment interaction - Abstract
Abstract: Cyclooxygenase-2 (COX-2) influences carcinogenesis through regulation of angiogenesis, apoptosis and cytokine expression. We aimed to evaluate association of COX-2 polymorphisms with predisposition to esophageal squamous cell carcinoma (ESCC), its phenotype variability and modulation of environmental risk in northern Indian population. We genotyped 174 patients with ESCC and 216 controls for COX-2 gene polymorphisms (−765G>C; −1195G>A; −1290A>G; 3′UTR 8473T>C) using PCR-RFLP. Data were statistically analyzed using chi-square test and logistic regression model. COX-2 −765C allele carriers were at increased risk for ESCC (OR=1.66; 95% CI=1.08–2.54; P =0.004). However, −1195G>A; −1290A>G; 3′UTR 8473T>C polymorphisms of COX-2 gene were not significantly associated with ESCC. We observed significantly enhanced risk for ESCC due to interaction between COX-2 −1195GA×−765GC+CC genotypes (OR=4.60; 95% CI=1.63–13.01; P =0.004). High risk to ESCC was also observed with respect to COX-2 haplotypes, A−1290G−1195C−765T8473 and A−1290A−1195C−765T8473 [OR=3.35; 95% CI=0.83–13.44; P =0.089; OR=4.28; 95% CI=0.43–42.40; P =0.246] however, it was not statistically significant. Stratification of subjects based on gender showed that females were at higher risk for ESCC due to COX-2 −765C carrier genotypes (OR=2.97; 95% CI=1.23–7.18; P =0.016). In association of genotypes with clinical characteristics, −765C carrier genotype conferred risk of ESCC in middle third of esophagus (OR=1.78; 95% CI=1.08–2.93; P =0.023). In case-only analysis, interaction of environmental risk factors and COX-2 genotypes did not further modulate the risk for ESCC. In summary, COX-2 −765G>C polymorphism confers ESCC susceptibility particularly in females and patients with middle third anatomical location of the tumor. Interaction of COX-2 −1195GA and −765C carrier genotypes also modulates ESCC risk. [Copyright &y& Elsevier]
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- 2009
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26. IL-1 gene polymorphisms and genetic susceptibility of gallbladder cancer in a north Indian population
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Vishnoi, Monika, Pandey, Sachchida Nand, Choudhuri, Gourdas, and Mittal, Balraj
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GENETIC polymorphisms , *GALLBLADDER diseases , *GALLBLADDER cancer , *GALLSTONES , *INTERLEUKIN-1 , *CYTOKINES , *CANCER patients , *THERAPEUTICS - Abstract
Abstract: Long-standing gallstones are generally present in 65–80% patients of gallbladder cancer (GBC). It has also been suggested that inflammation caused by gallstones may be involved in the development of GBC. Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1 beta (IL-1B) are proinflammatory cytokine genes at the interleukin-1 locus, and polymorphisms of these genes have been associated with various inflammatory diseases. The aim of this study was to investigate whether polymorphism in the IL-1RN and IL-1B genes are associated with GBC patients with and without gallstones. Polymorphisms within the IL-1RN 86–base pair VNTR (variable number tandem repeat) and IL-1B (−511C → T) were genotyped using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism in 166 healthy subjects and 124 GBC patients. The frequency of the IL-1RN, VNTR 2/2 genotype was significantly higher in GBC patients [P = 0.017; odds ratio (OR) = 3.25; 95% confidence interval (CI) = 1.23–8.58]. CC genotype and ‘C’ allele of the –511IL-1B C → T polymorphism also showed high risk for GBC (P = 0.033; OR = 3.36; 95%CI = 1.52–7.43, P = 0.047, OR = 1.41; 95%CI = 1.00–1.98, respectively). The higher cancer risk due to the IL-1RN, 2/2 genotype was observed in GBC patients with or without stones (P = 0.038; OR = 3.58; 95%CI = 1.08–11.65, P = 0.035; OR = 3.33; 95%CI = 1.08–10.61). Risk due to the CC genotype of IL-1B, however, was confined to GBC patients harboring gallstones (P = 0.0003; OR = 6.92; 95%CI = 2.65–18.03). The haplotype 1/C of IL-1RN and IL-1B was found to confer a significantly enhanced risk of GBC in cancer patients with gallstones (P = 0.022; OR = 2.19; 95%CI = 1.12–4.27), while higher risk resulting from 2/C haplotype was of borderline significance (P = 0.061; OR = 3.04; 95%CI = 0.95–9.70). Individuals with 1/C and 2/C haplotypes of IL-1RN VNTR and –511IL-1B C → T polymorphisms were more susceptible to develop GBC with gallstones compared to healthy controls in north India. [Copyright &y& Elsevier]
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- 2008
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27. Genetic susceptibility of epidermal growth factor +61A>G and transforming growth factor β1 -509C>T gene polymorphisms with gallbladder cancer
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Vishnoi, Monika, Pandey, Sachchida Nand, Modi, Dinesh Raj, Kumar, Ashok, and Mittal, Balraj
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CYTOKINES , *PEPTIDES , *CANCER patients , *GALLSTONES - Abstract
Summary: Epidermal growth factor (EGF) and transforming growth factor β1 (TGFβ1) play important roles in tumor biology. Single nucleotide polymorphisms in EGF and TGFB1 genes alter the expression of these growth factors and influence the tumorigenesis process. The aim of our present study was to determine the association of EGF+61A>G (rs4444903) and TGFB1-509C>T (rs1800469) gene polymorphism with susceptibility to gallbladder cancer (GBC). The present case–control association study was carried out in 126 confirmed GBC patients and 190 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. The GG genotype of EGF+61A>G was significantly associated with GBC [p = 0.012, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.19–4.15] in comparison to healthy subjects. Analysis based on gender indicated risk due to GG genotype was limited to female GBC patients (p = 0.003, OR = 3.45, 95% CI = 1.52–7.82). Upon stratification of GBC patients on the basis of the presence or absence of gallstones, the risk due to EGF polymorphism was not modulated by the status of gallstones. The TGFB1-509C>T polymorphism was not associated with GBC. Also, we did not find any association of this polymorphism when GBC patients were subdivided on the basis of gender. However, after stratification of GBC patients on the status of gallstones, we determined that the CT genotype of TGFB1 was associated with increased risk of GBC without gallstones (p value = 0.030, OR = 2.90, 95% CI = 1.26–6.69). Furthermore, the combination of the GG genotype of EGF and the CT genotype of TGFB1 demonstrated synergistic increase in risk of GBC.In conclusion, the higher producing +61G allele of EGF and -509 CT genotype of TGFB1 synergistically increase the susceptibility of gallbladder cancer (p value = 0.003). Further study in large samples size is required to confirm our findings. [Copyright &y& Elsevier]
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- 2008
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28. Potential influence of interleukin-1 haplotype IL-1β-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: A case–control study
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Upadhyay, Rohit, Jain, Meenu, Kumar, Shaleen, Ghoshal, Uday C., and Mittal, Balraj
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INTERLEUKIN-1 , *GENETIC polymorphisms , *POLYMERASE chain reaction , *DNA polymerases - Abstract
Summary: Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population. [Copyright &y& Elsevier]
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- 2008
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29. Association of Toll-like receptor–4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions
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Achyut, B.R., Ghoshal, Uday C., Moorchung, Nikhil, and Mittal, Balraj
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GASTRITIS , *GENETIC polymorphisms , *GASTROENTERITIS , *HELICOBACTER pylori - Abstract
Summary: A Toll-like receptor–4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+ strains of H. pylori are known to be associated with gastroduodenal diseases. Therefore we aimed to evaluate association of TLR-4 substitutions and CagA seropositivity with gastritis and precancerous lesions in a northern Indian population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)–positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD were also screened for H. pylori infection using modified Giemsa staining and anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200 asymptomatic control subjects were genotyped for TLR-4 substitutions using polymerase chain reaction–restriction fragment length polymorphism. We observed that frequencies of TLR-4 Asp299Gly variants were comparable between patients and control subjects, and also between positive and negative groups of precancerous lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008) and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4 399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023, OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions. CagA positivity may be a risk factor for lymphoid follicle development but not for other precancerous lesions in a northern Indian population. [Copyright &y& Elsevier]
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- 2007
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30. Role of BCL2 (ala43thr), CCND1 (G870A) and FAS (A-670G) polymorphisms in modulating the risk of developing esophageal cancer
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Jain, Meenu, Kumar, Shaleen, Lal, Punita, Tiwari, Anu, Ghoshal, Uday C., and Mittal, Balraj
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GENETIC polymorphisms , *CANCER risk factors , *ESOPHAGEAL cancer , *POPULATION genetics , *GENETIC research - Abstract
Abstract: Background: Perturbations in the cell cycle and apoptotic genes have been implicated in human malignancies. A study of BCL2 ala43thr, CCND1 G870A and FAS A-670G gene polymorphisms was undertaken to explore their role in influencing the susceptibility for development of esophageal cancer. Methods: A total of 151 patients and age and gender matched 201 controls were investigated for BCL2 ala43thr, CCND1 G870A and FAS A-670G polymorphisms by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results: The ala43ala genotype of BCL2 anti-apoptotic gene was significantly associated with risk of developing esophageal cancer (OR 2.1, 95%CI=1.0–4.4, P =0.03), more so in males (OR 2.6, 95%CI= P =0.03). In CCND1 G870A polymorphism, the AA genotype was marginally associated with higher risk of esophageal cancer (OR 1.5, 95%CI=0.98–2.4, P =0.05). No significant differences in genotype frequencies of FAS A-670G polymorphism were seen between esophageal cancer patients and controls (P =0.32). Interaction of BCL2 ala43ala, CCND1 870AA and FAS -670AA genotypes did not increase the risk multiplicatively. Association with clinical characteristics showed BCL2 ala43ala genotype to be at increased risk for developing tumors in the middle third location (OR 2.3, 95%CI=1.0–5.3, P =0.03), while patients with CCND1 870AA genotypes were at higher risk for the development of cancer in the upper third location (OR 3.8, 95%CI=1.6–9, P =0.002). BCL2 ala43ala genotype did not modulate the cancer risk in tobacco users. However, patients with CCND1 870AA and FAS -670AA genotypes were associated with a significantly lower number of smoking and chewing pack-years, suggesting a dose-dependent interaction in the risk for esophageal cancer (P =0.005). Conclusion: There appears to be an influence of BCL2 ala43ala and CCND1 870AA genotypes on esophageal cancer phenotype, particularly with regard to tumor location, which supports the theory of prevalence of site-specific genetic alterations. FAS A-670G was not associated with the risk of developing esophageal cancer. Gene–environment interaction analysis showed cancer susceptibility in CCND1 870AA and FAS -670AA genotype to be influenced by quantity of tobacco. [Copyright &y& Elsevier]
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- 2007
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31. GSTT1, GSTM1 and GSTP1 genetic polymorphisms and interaction with tobacco, alcohol and occupational exposure in esophageal cancer patients from North India
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Jain, Meenu, Kumar, Shaleen, Rastogi, Neeraj, Lal, Punita, Ghoshal, Uday C., Tiwari, Anu, Pant, Mohan C., Baiq, Mirza Q., and Mittal, Balraj
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CANCER patients , *GENETIC polymorphisms , *ESOPHAGEAL cancer - Abstract
Abstract: Glutathione S-transferases(GSTs) are detoxification enzymes that provide critical defense against carcinogens. Our hypothesis was that altered frequencies of GST genotypes and environmental exposures might be associated with increased susceptibility for the development of esophageal cancer. A total of 100 esophageal cancer patients and 137 age and gender matched healthy controls were analyzed for GST polymorphisms. Frequencies of GSTT1 null, GSTM1 null and GSTP1 genotypes did not differ between patients and controls. However, a two-fold risk was observed for GSTM1 null genotype in adenocarcinoma (OR(odds ratio) 2.1; 95% CI(confidence intervals)=0.53–8.6). Further, we used a case only design to study gene–environment interactions in esophageal cancer. In patients with smoking habits, GSTM1 null and GSTP1 ile/ile genotype were at higher risk for esophageal cancer (OR 1.5; 95% CI=0.50–4.4 and OR 1.3; 95% CI=0.40–3.5), respectively. A moderate risk for cancer was observed from alcohol usage along with GSTM1 null(OR 1.3; 95% CI=0.50–3.6) and GSTP1 val/val genotypes(OR 1.2; 95% CI=0.20–5.7). Interaction of GST genotypes with occupational exposure did not affect risk for esophageal cancer. These findings suggest that genetic polymorphisms of GSTT1, GSTM1, and GSTP1 are not associated with higher risk of esophageal cancer. However, interaction of smoking or alcohol with GSTM1 null or GSTP1 ile/ile moderately increases the risk for esophageal cancer in North Indian population. [Copyright &y& Elsevier]
- Published
- 2006
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32. Y chromosome micro-deletions in idiopathic infertility from Northern India
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Mittal, Rama Devi, Singh, Gunjana, Srivastava, Aneesh, Pradhan, Mandakini, Kesari, Akanchha, Makker, Annu, and Mittal, Balraj
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GENES , *GENETICS , *SPERMATOGENESIS , *MALE infertility , *Y chromosome - Abstract
Azoospermia factor locus (AZF) is assumed to contain the genes responsible for spermatogenesis. Deletions in these genes are thought to be pathologically involved in some cases of male infertility associated with azoospermia or oligozoospermia. An attempt was made to establish the prevalence of micro-deletions on the Y chromosome in 79 infertile North Indians with azoospermia and oligozoospermia. Detail clinical examinations as well as endocrinological parameters were also done. Polymerase chain reaction (PCR) micro-deletion analysis was done in 79 infertile men. For this, genomic DNA was extracted from the peripheral blood. Seven sets of primers were used encompassing AZFa, AZFb and AZFc regions. Micro-deletions in five of the 79 cases (6.3%) showed deletions of at least one of the STS markers. Deletions were detected with known and unknown aetiology and at least in one of the infertile male with varicocele. AZF micro-deletions seen in idiopathic infertile males suggest the need for molecular screening in non-idiopathic cases. [Copyright &y& Elsevier]
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- 2004
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33. PD-0011HIGHER RISK OF GENETIC VARIANTS OF CYP1A1 WITH GALLSTONE-INDEPENDENT GALLBLADDER CANCER SUSCEPTIBILITY IN NORTH INDIA.
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Kumar, Ashok, Sharma, Kiran, Mishra, Sanjeev, and Mittal, Balraj
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GALLSTONES , *GALLBLADDER cancer , *DISEASE susceptibility , *CANCER risk factors , *CANCER prognosis , *CANCER genetics - Published
- 2013
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34. Null association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility and prognosis of Esophageal cancer in north Indian population and meta-analysis
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Umar, Meenakshi, Upadhyay, Rohit, Kumar, Shaleen, Ghoshal, Uday Chand, and Mittal, Balraj
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ESOPHAGEAL cancer , *OXIDOREDUCTASE genetics , *GENETIC polymorphisms , *META-analysis , *PROGNOSIS ,CANCER susceptibility - Abstract
Abstract: Introduction: NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2), involved in detoxification of environmental carcinogens and activation of chemotherapeutic agents, are supposed to play critical role in carcinogenesis. So, we aimed to investigate the association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility and prognosis of Esophageal cancer (EC) in north Indian population. We also performed Meta analysis of published literatures on NQO1 609C>T polymorphism to systematically evaluate its association with EC. Methods: We genotyped NQO1 609C>T and NQO2 -3423G>A polymorphisms in 200 incident EC cases (including 150 follow-up cases) and 200 controls using PCR RFLP based methods. Binary logistic regression was applied for risk estimation, while Kaplan Meier and Cox regression tests were applied for survival analysis. All Meta analysis tests were performed using MIX 2.0 software. Results: The present study did not find any significant association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC or its clinical phenotypes (histopathology, tumor location or lymph node metastasis) or interactions with lifestyle risk factors (tobacco usage, smoking, alcohol habit and occupational exposures). Meta analysis of NQO1 polymorphism also indicated null association of the polymorphism with EC overall or with cancer cases stratified by tumor histopathology/ethnicity. Moreover, no prognostic implication of both polymorphisms was observed in EC. Conclusion: NQO1 609C>T and NQO2 -3423G>A polymorphisms do not seem to play any significant role in susceptibility or prognosis of EC in north Indian population and results of Meta-analysis further reinforces null association of NQO1 609C>T polymorphism with EC susceptibility. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
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