Use this URL to cite or link to this record in EThOS:
Title: The role of genetic factors in breast cancer aetiology
Author: Hammond, Victoria Naomi
ISNI:       0000 0004 2693 3546
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2010
Availability of Full Text:
Access from EThOS:
Access from Institution:
Breast cancer is the most common cancer in women and is also the leading cause of cancer mortality in women. There are several known risk factors for breast cancer including genetic factors which account for at least 25% of the incidence of breast cancer, although only a small proportion of this is a result of mutations in known high penetrance susceptibility genes. The majority of genetic risk is now thought to be due to common genetic variants, for example single nucleotide polymorphisms (SNPs). We investigated whether SNPs in candidate genes, with a biological reason for being of interest to study in relation to breast cancer, were correlated with the development of tumours with a certain phenotype, such as grade, lymph node involvement, oestrogen receptor status and the presence of distant metastases. We genotyped 206 SNPs across 30 candidate genes in 1001 patients. Association was performed using Cochran-Armitage trend test and 2-by-3 tables of disease by genotype. We replicated observations from previous studies such as the association of SNPs in FGFR2, TNRC9 and ATM with oestrogen receptor status and identified novel associations of SNPs in the oestrogen receptor gene and matrix metalloproteinase-9 gene (MMP-9) with grade and presence of distant metastasis respectively. The function of two promoter SNPs in MMP-9 were further investigated using luciferase reporter gene assays. The C allele of rs3918242 had a 1.5 fold increase in MMP-9 expression in MDA-MB- 231 cells and the A allele of rs3918241 showed a slight increase in MMP-9 expression in MCF-7 and NIH-3T3 cell lines although not significant. The novel results identified need to be replicated for validation but this study provides evidence that common genetic variants play a role in predisposing to certain tumour types.
Supervisor: Eccles, Diana Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer) ; QH426 Genetics