published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Jiang, Jieying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 170-186). / Abstract also in Chinese. / ACKNOWLEDGEMENT --- p.II / ABBREVIATIONS --- p.III / ABSTRACT OF THESIS ENTITLED: --- p.VI / 摘要 --- p.IX / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Individual variations of blood sex steroid levels and their determinants --- p.1 / Chapter 1.1.1 --- Introduction to Sex steroids --- p.1 / Chapter 1.1.2 --- Androgens --- p.1 / Chapter 1.1.2.1 --- Types of androgens --- p.1 / Chapter 1.1.2.2 --- Androgens plasma concentration and relative biological potencies --- p.2 / Chapter 1.1.2.3 --- Androgen biosynthesis and metabolism --- p.3 / Chapter 1.1.2.4 --- Testosterone transportation in plasma --- p.6 / Chapter 1.1.2.5 --- Measurement of free testosterone --- p.7 / Chapter 1.1.2.6 --- The hypothalamus-pituitary-testicular axis and testosterone secretion --- p.8 / Chapter 1.1.2.7 --- Androgen action --- p.10 / Chapter 1.1.2.8 --- Androgen biological function and diseases in men --- p.11 / Chapter 1.1.3 --- Estrogen biological function and diseases in men --- p.12 / Chapter 1.1.4 --- Factors influencing circulating sex steroid levels --- p.13 / Chapter 1.1.4.1 --- Genetic determinants affecting sex steroid levels --- p.15 / Chapter 1.2 --- Genetic variants in sex steroid metabolic pathway and hepatocellular carcinoma (HCC) --- p.18 / Chapter 1.2.1 --- Epidemiology of HCC --- p.18 / Chapter 1.2.2 --- Etiological factors of HCC --- p.22 / Chapter 1.2.3 --- The male predominance in HCC --- p.24 / Chapter 1.2.4 --- Genetic predisposition to HCC --- p.26 / Chapter CHAPTER 2 --- PART A STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH SEX STEROID LEVELS --- p.28 / Chapter 2.1 --- Introduction --- p.28 / Chapter 2.1.1 --- Candidate genes association with sex steroid levels --- p.28 / Chapter 2.1.2 --- Genes involved in androgen metabolism --- p.29 / Chapter 2.1.2.1 --- SRD5A --- p.29 / Chapter 2.1.2.2 --- HSD3B1 --- p.30 / Chapter 2.1.2.3 --- HSD17B2 --- p.31 / Chapter 2.1.2.4 --- AKR1C3 and AKRlC4 --- p.31 / Chapter 2.1.2.5 --- AKR1D1 --- p.32 / Chapter 2.1.3 --- Genes involved in estrogen metabolism --- p.32 / Chapter 2.1.3.1 --- CYP19A1 --- p.32 / Chapter 2.1.3.2 --- Other genes involved in estrogen metabolism --- p.33 / Chapter 2.1.4 --- Association of sex steroid related genes and blood concentrations of sex steroid levels --- p.33 / Chapter 2.1.4.1 --- Genes involved in androgen metabolic pathway and association with sex steroid levels --- p.33 / Chapter 2.1.4.2 --- Genes involved in estrogen metabolic pathway and association with sex steroid levels --- p.36 / Chapter 2.1.5 --- Aims of the study (Part A) --- p.37 / Chapter 2.2 --- Materials and methods --- p.38 / Chapter 2.2.1 --- Study subjects and biological samples --- p.38 / Chapter 2.2.2 --- TagSNP selection --- p.39 / Chapter 2.2.3 --- Genotyping of tagging SNPs --- p.41 / Chapter 2.2.4 --- Genotyping methods comparison --- p.52 / Chapter 2.2.5 --- Statistics --- p.53 / Chapter 2.3 --- Results --- p.54 / Chapter 2.3.1 --- Characteristics of study population --- p.54 / Chapter 2.3.2 --- Replication study for the association of CYP19A1 --- p.55 / Chapter 2.3.2.1 --- Association of the SNP rs2470152 and rs2899470 with serum estrogen and testosterone levels --- p.55 / Chapter 2.3.2.2 --- Halotype analysis and haplotype association in the tertile groups --- p.61 / Chapter 2.3.2.3 --- Haplotype construction of 3 SNPs --- p.63 / Chapter 2.3.3 --- SRD5A1 --- p.65 / Chapter 2.3.3.1 --- Association of SRD5A1 and sex steroid levels --- p.65 / Chapter 2.3.3.2 --- Haplotype analysis and haplotype association in the tertile groups --- p.71 / Chapter 2.3.4 --- SRD5A2 --- p.72 / Chapter 2.3.4.1 --- Association of SRD5A2 and sex steroid levels --- p.72 / Chapter 2.3.4.2 --- Haplotype association analysis of SRD5A2 in tertile groups --- p.76 / Chapter 2.3.5 --- HSD3B1 --- p.77 / Chapter 2.3.5.1 --- Association of HSD3B1 and sex steroid levels --- p.77 / Chapter 2.3.6 --- HSD17B2 --- p.80 / Chapter 2.3.6.1 --- Association of HSD17B2 and sex steroid levels --- p.80 / Chapter 2.3.6.2 --- Halotype association analysis of HSD17B2 in the tertile groups --- p.87 / Chapter 2.3.7 --- AKR1C4 --- p.89 / Chapter 2.3.7.1 --- Association of AKR1C4 and sex steroid levels --- p.89 / Chapter 2.3.7.2 --- Halotype association analysis of AKR1C4 in the tertile groups --- p.93 / Chapter 2.3.8 --- AKR1D1 --- p.94 / Chapter 2.3.8.1 --- Association of AKR1D1 and sex steroid levels --- p.94 / Chapter 2.3.8.2 --- Haplotype association analysis of AKR1D1 in the tertile groups --- p.99 / Chapter 2.3.9 --- AKR1C3 --- p.100 / Chapter 2.3.9.1 --- Association of AKR1C3 and sex steroid levels --- p.100 / Chapter 2.3.9.2 --- Haplotype association analysis of AKR1C3 in the tertile groups --- p.104 / Chapter 2.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and metabolites levels in blood --- p.105 / Chapter 2.4 --- Discussion --- p.106 / Chapter 2.4.1 --- SRD5A and sex steroid levels --- p.106 / Chapter 2.4.2 --- HSD17B2 and sex steroid levels --- p.110 / Chapter 2.4.3 --- "AKR1D1, AKR1C4, AKR1C3 and catabolic intermediates of sex steroids" --- p.112 / Chapter 2.4.4 --- HSD3B1 and sex steroid levels --- p.114 / Chapter 2.4.4 --- CYP19A1 and sex steroid levels --- p.114 / Chapter CHAPTER 3 --- PART B STUDY: GENETIC VARIATIONS IN SEX STEROID METABOLIC PATHWAY AND ASSOCIATION WITH HCC --- p.119 / Chapter 3.1 --- Introduction --- p.119 / Chapter 3.1.1 --- Previous genetic association studies of HCC on sex steroid metabolic pathways --- p.119 / Chapter 3.1.2 --- Previous genetic association studies of HCC in other pathways --- p.120 / Chapter 3.1.3 --- "Association of sex steroid related genes and other cancers, like prostate cancer" --- p.121 / Chapter 3.1.4 --- Aims of the study (Part B) --- p.123 / Chapter 3.2 --- Materials and method --- p.125 / Chapter 3.2.1 --- "Study subjects, Genomic DNA extraction" --- p.125 / Chapter 3.2.2 --- Tissue specimen and cell lines --- p.125 / Chapter 3.2.3 --- TagSNP selection --- p.126 / Chapter 3.2.4 --- Genotyping of tagging SNPs --- p.126 / Chapter 3.2.5 --- Statistics --- p.127 / Chapter 3.2.6 --- Extraction of RNA and Reverse-Transcription-PCR --- p.128 / Chapter 3.3 --- Results --- p.130 / Chapter 3.3.1 --- SRD5A1 --- p.130 / Chapter 3.3.1.1 --- SRD5A1 polymorphisms and risk of HCC --- p.130 / Chapter 3.3.2 --- SRD5A2 --- p.134 / Chapter 3.3.2.1 --- SRD5A2 polymorphisms and risk of HCC --- p.134 / Chapter 3.3.2.2 --- Haplotype analysis --- p.136 / Chapter 3.3.3 --- HSD3B1 --- p.137 / Chapter 3.3.3.1 --- HSD3B1 polymorphisms and risk of HCC --- p.137 / Chapter 3.3.3.2 --- Haplotype analysis --- p.139 / Chapter 3.3.4 --- HSD17B2 --- p.140 / Chapter 3.3.4.1 --- HSD17B2 polymorphisms and risk of HCC --- p.140 / Chapter 3.3.4.2 --- Haplotype analysis --- p.143 / Chapter 3.3.5 --- CYP19A1 --- p.144 / Chapter 3.3.5.1 --- CYP19A1 polymorphisms and risk of HCC --- p.144 / Chapter 3.3.5.2 --- Haplotype analysis --- p.146 / Chapter 3.3.6 --- AKR1C4 --- p.147 / Chapter 3.3.6.1 --- AKR1C4 polymorphisms and risk of HCC --- p.147 / Chapter 3.3.6.2 --- Haplotype analysis --- p.148 / Chapter 3.3.7 --- AKR1D1 --- p.149 / Chapter 3.3.7.1 --- AKR1D1 polymorphisms and risk of HCC --- p.149 / Chapter 3.3.7.2 --- Haplotype analysis --- p.150 / Chapter 3.3.8 --- AKR1C3 --- p.151 / Chapter 3.3.8.1 --- AKR1C3 polymorphisms and risk of HCC --- p.151 / Chapter 3.3.8.2 --- Haplotype analysis --- p.152 / Chapter 3.3.9 --- mRNA expression study of the 5 α -reductase isoforms --- p.153 / Chapter 3.3.9.1 --- Expression of SRD5A1 and SRD5A2 mRNAin HCC patients --- p.153 / Chapter 3.3.9.2 --- Expression of SRD5A1 and SRD5A2 mRNAin prostate and HCC cell lines --- p.154 / Chapter 3.3.10 --- Overall association of polymorphisms in sex steroid metabolism genes and risk of HCC --- p.154 / Chapter 3.3.11 --- GMDR analysis --- p.156 / Chapter 3.4 --- Discussion --- p.159 / Chapter 3.4.1 --- 5 α-reductase and risk of HCC --- p.159 / Chapter 3.4.1.1 --- SRD5A2 --- p.160 / Chapter 3.4.1.2 --- SRD5A1 --- p.161 / Chapter 3.4.2 --- Other genes and association with HCC --- p.162 / Chapter 3.4.2.1 --- HSD17B2 and risk of HCC --- p.162 / Chapter 3.4.2.2 --- "HSD3B1, AKR1C3, AKR1C4, AKR1D1 and risk of HCC" --- p.163 / Chapter 3.4.2.3 --- CYP19A1 and risk of HCC --- p.164 / Chapter 3.4.3 --- Gene-Gene interactions associated with HCC --- p.165 / Chapter CHAPTER 4 --- CONCLUSIONS AND PROSPECT FOR FUTURE WORK --- p.166 / Chapter 4.1 --- Conclusion --- p.166 / Chapter 4.2 --- Future works and prospect --- p.169 / REFERENCES --- p.170