South Africa is unique in the arena of Intersex, in that for unknown reasons we have a very high percentage of ovotesticular DSD (True Hermaphrodite). Whereas ovotesticular DSD is the least common cause of hermaphroditism in other parts of the world, it is the most common cause of hermaphroditism in South Africa. There have been several studies in the past to determine the cause of ovotesticular DSD in our population but none of these studies found appropriate answers. The current state of understanding implicates signaling and signal transduction molecules and transcription factors suggesting that it is likely not all of the genetic factors involved have already been identified. It was hypothesized that exome sequencing of individuals with DGDs will identify new mutations and genes for these conditions. Therefore, this study aims to identify additional genes that are associated with ovotesticular DSD. By using a whole-genome sequencing approach we expected to be able to identify rare variants with this condition and determine the prevalence of mutations in these genes in the ovotesticular DSD population. After obtaining informed consent, blood specimen was obtained from eleven out of fifteen patients who had histological diagnosis of Ovotesticular DSD at the Red Cross War Memorial Hospital over a 10 year period. Blood specimen was also obtained from the biological parents of these children and sent to the Ostrer laboratory for whole genome sequencing and analysis. At the Ostrer laboratory, high quality DNA was extracted from blood for all of subjects and lymphoblastoid cell lines were created. Following sample preparation using the Illumina library preparation kit, sequencing was accomplished using paired-end sequencing technology on an Illumina HiSeq2000 sequencer. The data from the Illumina sequencers was analyzed first using the Illumina sequencing data analysis pipeline for quality control. Paired end reads were aligned to the Human Reference Genome (NCBI Build 36) using the BWA software. Each alignment was assigned a mapping quality score by BWA, which is the Phredscaled probability that a read is misaligned. The basic functional annotation of SNPs/Indels is performed by ANNOVAR. The clinical features of these patients was consistent with those found by other studies on Ovotesticular DSD in South Africa and it also showed the same pattern of variation to the clinical features of Ovotesticular DSD from other parts of the world. Similar to previous South African studies, this study found no convincing gene mutations as the possible etiology of Ovotesticular DSD in South Africa. Whiles gene mutations such as duplication of SOX 9 have been found in patients with XX Ovotesticular DSD from outside South Africa, this study could not identify any such mutations. This further adds to the suspicion that the unique features of Ovotesticular DSD in South Africa suggests a different etiology from that of other parts of the world. In conclusion, the etiology of Ovotesticular DSD in South Africa still remains elusive. It is however possible that a genetic mutation may be found from a more critical analysis of the genome of the patients and their parents.

Includes bibliographical references ( leaves 38-39). / This is a retrospective study of male patients that suffered gunshot wounds to the extental genitalia from August 1997 to September 2006. This study also reviews the literature and compares treatment methods locally and internationally.

No description available.

Includes list of publications and presentations by the author. Bibliography: leaves 166-194. A collection of laboratory and clinical studies in paediatric urology, including prospective and retrospective patient series, case reports of rare conditions. Also, technical innovations are documented and reviewed in light of international experience.

Thesis (M.Med.Sc.) -- University of Adelaide, Dept. of Paediatrics, 2001. / Includes list of publications and presentations by the author. Bibliography: leaves 166-194.

No description available.

The aim of this thesis was to investigate the involvement of the insulin-like growth factor- and the one-carbon metabolism pathways in prostate cancer aetiology, studying both circulating biomarkers and genetic variation. Papers included in the thesis were conducted within the case-control study CAncer Prostate in Sweden (CAPS), and the two prospective studies European Prospective Investigation into nutrition and Cancer (EPIC), and Northern Sweden Health and Disease Cohort (NSHDC). In paper I, we investigated the relation between genetic variants of the IGF1 gene and prostate cancer risk within the CAPS study. We found that a common haplotype within the 3’ region of the IGF1 gene is associated with increased prostate cancer risk. In paper II, we investigated if the variants of the IGF1 gene that were associated with prostate cancer risk in paper I, are also associated with circulating levels of IGF1. Circulating levels of IGF1 were analysed in controls from the CAPS study and three haplotype tagging SNPs (htSNPs) were genotyped in subjects from the NSHDC study in which circulating IGF1 had previously been analysed. The genetic variants previously associated with increased prostate cancer risk were now also found to be associated with elevated levels of circulating IGF1. We concluded that variation in the 3’ region of the IGF1 gene affects prostate cancer risk by influencing circulating levels of IGF1. In paper III, we investigated if variants of the IGFBP1, IGFBP3 and IGFALS genes are associated with i) prostate cancer risk, ii) circulating concentrations of total and intact IGFBP3, and iii) prostate cancer-specific survival probability. In addition, we investigated if circulating concentrations of total and intact IGFBP3 are associated with prostate cancer-specific survival probability. No association between genetic variation and overall prostate cancer risk or survival was observed, but we found a strong association between elevated levels of intact IGFBP3 and increased risk of prostate cancer-specific death. We could, however, not exclude that this association was confounded by treatment or by the tumour. In paper IV, we investigated if circulating levels of folate and vitamin B12 are associated with prostate cancer risk within the EPIC study. We observed no associations between levels of folate, vitamin B12 and overall prostate cancer risk, but elevated levels of vitamin B12 were associated with increased risk of advanced stage disease. In paper V, we investigated if circulating levels of ten B-vitamins and related metabolites within the one-carbon metabolism pathway are associated with prostate cancer risk within the NSHDC study. Overall positive associations with prostate cancer risk were observed for levels of choline, vitamin B2 and vitamin B12, and inverse associations were observed for levels of homocysteine and MMA. We also observed a biologically plausible risk modification by smoking status on the association between vitamin B12 and risk; in non-smokers vitamin B12 was positively associated with risk, whereas the association between vitamin B12 and risk was inverse or null in ever/current-smokers. In summary, our results suggest that genetic variation of the IGF1 gene affects prostate cancer risk by affecting circulating levels of IGF1. The association between circulating concentrations of intact IGFBP3 and prostate cancer-specific survival is intriguing, but further studies are needed to conclude if this association is caused by confounding. We also observed associations between several factors of one-carbon metabolism and risk, but these associations were statistically week and require confirmation in other prospective studies.

No description available.

Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited.  Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI).  Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can.  Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer.   Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors.  Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer.  Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xiii, 154 p.; also includes graphics (some col.). Includes abstract and vita. Advisor: Sheryl L. Szeinbach, College of Pharamcy. Includes bibliographical references (p. 139-154).