Host genetic determinants of cervical cancer, HPV and HSV-2 infection

Cervical cancer (CaCx), caused by human papillomavirus (HPV), is the second most common cancer in women worldwide. Although large numbers of women get HPV-infected only a small fraction develop CaCx pointing to co-factors including host genetics playing a role. The aim of this thesis was to investigate the role of genetic polymorphisms in the cell death pathway genes, Fas, FasL and CASP8 in CaCx, pre-cancers and HPV infection. The genes have also been investigated in herpes simplex virus type-2 (HSV-2) infection, a co-factor for developing CaCx. Another gene involved in macrophage recruitment, CCR2 was also investigated. A case-control approach was used on South African black and mixed-ancestry population. Genotyping of the desired polymorphisms from peripheral blood was achieved using TaqMan assay, PCR-SSP and PCR-RFLP. Results were analysed using R, Stata 9 and Haploview 4.2. We show that genetic polymorphisms in these genes are differentially associated to CaCx, pre-cancers, HPV infection and HSV-2 infection. This is the first study reporting the role of Fas, FasL, CASP8 and CCR2 polymorphisms in CaCx in an African population and a non-HLA host genetic link to HSV-2 infection.