LIFE09200604007 Tabish - Homi Bhabha National Institute

More documents

Recommendations

Info

Review of Literature of 31 published case-control associations of GSTT1 null genotype along with GSTM1 null genotype with head and neck cancer risk was observed 149 . Apart from this, in Indian population as well GSTT1 null genotype has emerged as associated with risk of upper aero digestive tract cancers 143, 150 . On the contrary a large Indian study has shown GSTT1 to be significantly protective in oral cancer patients with tobacco habit 151 . GSTP1 (Glutathione-S-Transferase-Pi 1) The gene encodes an enzyme belonging to GST pi class. GSTP1-exon5 Ile 105 Val polymorphism is extensively studied in terms of association with cancer 152 . This polymorphism is reported to confer risk of upper aero digestive tract cancers among Indians along with other GSTT1 and GSTM1 polymorphism 153 . In addition GST profile may have a prognostic value since it is associated with the response to therapy in human malignancies 148, 154, 155 . GSTP1 Ile 105 Val polymorphism is found to be associated with modestly increased risk of second primary malignancy after index head and neck squamous cell carcinomas 44 . SULT1A1 (Sulfotransferase 1A1) The gene encodes sulfotransferase enzyme that belongs to phase II carcinogen detoxifying enzyme category. It catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and carcinogenic compounds resulting in increased polarity and solubility of the compound that facilitates excretion of carcinogens through bile or urine. SULT1A1-exon7 Arg 213 His polymorphism is very extensively studied and is found to be associated with head and neck cancer and lung cancer risk 156, 157 . Our study of meta-analysis of 33 case control studies showed His/His 213 genotype to confer significant risk UADT cancers 12 . MPO (Myeloperoxidase) It activates wide range of tobacco smoke procarcinogens such as benzo[a]pyrene and aromatic amines into activated carcinogens. The -463G>A SNP occurs in the MPO promoter region leading to decreased expression and activity 158 . The variant allele of MPO is shown to have mixed effect on cancer risk. It is reported that subjects bearing the A/G or A/A allele have a reduced risk to suffer from advanced lung cancer and esophageal cancer 159, 160 . Where as in other reports genetic effect of 48
Review of Literature MPO gene polymorphism is shown to slightly modify the risk of oral cavity cancer development 161, 162 . NAT2 (N-acetyltransferase 2) This gene encodes an enzyme that transfers acetyl group from acetyl coenzyme-A to the N-terminal group of carcinogenic compounds. It functions to both activate and deactivate aryl-amine, hydrazine drugs and carcinogens. Polymorphisms in this gene are associated with higher incidences of cancer and drug toxicity. There are three polymorphic sites in NAT2 gene that are very frequently reported and are found to be associated with conferring risk to cancer viz., NAT2-exon2 Ile 114 Thr, NAT2- exon2 Arg 197 Gln and NAT2-exon2 Gly 286 Glu. The NAT gene polymorphisms are associated with increased risk of oral and pharyngeal squamous cell carcinoma 163, 164 . These polymorphisms have been implicated as risk in case control study of oral and oropharyngeal cancer in whites 162 . These polymorphisms along with cigarette smoking and alcohol consumption confer oral squamous cell cancer risk 165 , A meta-analysis showed NAT2 slow acetylation may contribute to a risk factor for laryngeal cancer in Asians 166 . NAT2 polymorphism is also associated with development of second primary cancer in head and neck cancer individual 10 . Slow NAT2 activity is a risk factor possibly leading to the development of head and neck cancer in response to tobacco carcinogens 167 . EPHX1 (mEH, Microsomal epoxide hydrolase) This gene encodes a carcinogen metabolizing enzyme mEH (microsomal epoxide hydrolase) that converts epoxides from the degradation of aromatic compounds to trans-dihydrodiols which can be conjugated and excreted from the body. mEH-exon3 Try 113 His polymorphism was selected for present study as increased risk for head and neck cancer is associated with EPHX1-exon3 Tyr/His 113 and His/His 113 genotypes 141, 168 . In a recent comprehensive meta-analysis of 84 studies, EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers. It is described that low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas high EPHX1 activity may have a harmful effect 169 . 49
Page 1:
Genotype-Molecular Phenotype Correl
Page 7 and 8:
CONTENTS Page No Synopsis 1 List of
Page 9 and 10: Synopsis
Page 11 and 12: Synopsis Genotype-Molecular Phenoty
Page 13 and 14: Synopsis Materials and Methods: 1.
Page 15 and 16: Synopsis loading control. PCR produ
Page 17 and 18: Synopsis 7.1 Percent cell death aft
Page 19 and 20: Synopsis slides were then dried and
Page 21 and 22: Synopsis range 41.77% - 90.95% at 5
Page 23 and 24: Synopsis 5. Genotyping of genes: Ge
Page 25 and 26: Synopsis G2/M arrest and delaying e
Page 27 and 28: Synopsis may have an important bear
Page 29 and 30: Synopsis References: 1. Bobba, R.;
Page 31 and 32: Abbreviations MOPS : 3-(N-morpholin
Page 33 and 34: List of Figures Fig. 28: Percent re
Page 35 and 36: Chapter 1 Introduction
Page 37 and 38: Introduction In previous studies fr
Page 39 and 40: Introduction important carcinogenes
Page 41 and 42: Review of Literature The yet undeci
Page 43 and 44: Review of Literature Fig. 2: Incide
Page 45 and 46: Review of Literature sustained angi
Page 47 and 48: Review of Literature 2.6 Genotype p
Page 49 and 50: Review of Literature 2.7.2 Biologic
Page 51 and 52: Review of Literature Table 1: Steps
Page 53 and 54: Review of Literature future analysi
Page 55 and 56: Review of Literature Inefficient ce
Page 57 and 58: Review of Literature XRCC1 (X-ray r
Page 59: Review of Literature 2.9.2 Gene inv
Page 63 and 64: Review of Literature important role
Page 65 and 66: Materials and Methods Source of che
Page 67 and 68: Materials and Methods Method: EBV-t
Page 69 and 70: Materials and Methods Immunophenoty
Page 71 and 72: Materials and Methods with 500 μl
Page 73 and 74: Materials and Methods cDNA it can b
Page 75 and 76: Materials and Methods Cobalt-60 iso
Page 77 and 78: Materials and Methods specific bind
Page 79 and 80: Materials and Methods h half of the
Page 81 and 82: Materials and Methods phenol and th
Page 83 and 84: Materials and Methods 7. Filter ste
Page 85 and 86: Materials and Methods viz. EXO-SAP
Page 88 and 89: Materials and Methods Table 2: List
Page 90 and 91: Materials and Methods SMAD6 AREG HM
Page 92 and 93: Materials and Methods 3.9 Effect of
Page 94 and 95: Materials and Methods fresh eppendo
Page 96 and 97: Materials and Methods Power SYBR Gr
Page 98 and 99: Results Objective 1 To generate EBV
Page 100 and 101: Results Fig. 8: Frequency of second
Page 102 and 103: Results Table 6: Demographics of he
Page 104 and 105: Results Fig. 10: Cell population do
Page 106 and 107: Results Fig. 12: Cell surface marke
Page 108 and 109: Results 4.1.5 Expression of ATM gen
Page 110 and 111:
Results Objective 2 To compare the
Page 112 and 113:
Results Fig. 17: Standardization of
Page 114 and 115:
Results Fig. 19: Standardisation of
Page 116 and 117:
Results The cells were incubated fu
Page 118 and 119:
Results 4.2.3.1 Percent G2 delay af
Page 120 and 121:
Results 4.2.3.2 Effect of BPDE expo
Page 122 and 123:
Results Fig. 29: Comparison of perc
Page 124 and 125:
Results Fig. 31: Percent cell death
Page 126 and 127:
Results normalization with baseline
Page 128 and 129:
Results 4.2.5.2 Real time PCR valid
Page 130 and 131:
Results homozygous wild-type, heter
Page 132 and 133:
Results Fig. 36b: Electrophoresis o
Page 134 and 135:
Results Fig. 37a: Representative el
Page 136 and 137:
Results Table 13: Consolidated geno
Page 138 and 139:
Results LCL Genes NAT2(1) NAT2(2) N
Page 140 and 141:
Results Fig. 38: Distribution of Ge
Page 142 and 143:
Results Fig. 39: Various combinatio
Page 144 and 145:
Results Table 14: Genotype-phenotyp
Page 146 and 147:
Discussion Introduction Squamous ce
Page 148 and 149:
Discussion stimulated lymphocytes w
Page 150 and 151:
Discussion H2AX is currently the mo
Page 152 and 153:
Discussion or G2/M phase arrest. As
Page 154 and 155:
Discussion differential expression
Page 156 and 157:
Discussion DNA repair genes and MPN
Page 158 and 159:
Chapter 6 Summary and Conclusions
Page 160 and 161:
Summary and Conclusions Statistical
Page 162 and 163:
Bibliography 1. Dikshit, R.; Gupta,
Page 164 and 165:
Bibliography 43. Lei, D.; Sturgis,
Page 166 and 167:
Bibliography 76. Fry, R. C.; Svenss
Page 168 and 169:
Bibliography 115. Kote-Jarai, Z.; M
Page 170 and 171:
Bibliography 149. Hashibe, M.; Bren
Page 172 and 173:
Bibliography 183. Bergamaschi, D.;
Page 174 and 175:
Bibliography 216. Bondy, M. L.; Wan
Page 176 and 177:
Indian J Med Res 135, June 2012, pp
Page 178 and 179:
822 INDIAN J MED RES, JUNE 2012 mar
Page 180 and 181:
824 INDIAN J MED RES, JUNE 2012 (h)
Page 182 and 183:
826 INDIAN J MED RES, JUNE 2012 Tab
Page 184 and 185:
828 INDIAN J MED RES, JUNE 2012 lik
Page 186 and 187:
CASE REPORT Eben L. Rosenthal, MD,
Page 188 and 189:
FIGURE 2. Chromosomal breakage anal
Page 190 and 191:
FA along with ataxia telangiectasia
show all

LIFE09200604007 Tabish - Homi Bhabha National Institute

Create successful ePaper yourself

Delete template?

Save as template?