The genetic epidemiology of melanoma susceptibility and prognosis and investigations of causal pathway modelling in complex disease aetiology

[Truncated abstract] Genetic epidemiological studies are increasingly being used to investigate the role of genetic and environmental factors in common human disease aetiology, with the ultimate aims of control and prevention. This thesis investigated the association of candidate genes with melanoma susceptibility and prognosis in the Western Australian population. In addition, methods research into novel statistical methods to model causal pathways in epidemiological studies was undertaken. Australia has the highest incidence of cutaneous malignant melanoma in the world. Several melanoma-susceptibility genes have been identiffied, however a greater understanding of these genes and their interactions with environmental factors would lead to better interventions and control of the disease. The genetic determinants of melanoma progression, and therefore prognosis, are largely unknown. Knowledge of the genes which a ect melanoma progression and prognosis would aid in identifying individuals at risk of poorer prognosis, and may also elucidate the mechanisms underlying melanoma progression. The collection of population-based clinical, phenotypic and genetic data is integral in facilitating investigation into the genetic and environmental factors a ecting melanoma susceptibility and prognosis. This thesis involved the establishment of theWestern Australian Melanoma Health Study (WAMHS). The WAMHS is a population-based case-collection and linked biospecimen resource established to investigate the genetic epidemiology of melanoma. All eligible Western Australian adult cases of melanoma, diagnosed between January 2006 and September 2009 and noti ed to theWestern Australian Cancer Registry (WACR), were invited to participate in the study. Clinical and questionnaire- based phenotypic data and blood samples for extraction of DNA, RNA and serum were collected from consenting cases.