The association of host and genetic melanoma risk factors with Breslow thickness in the Western Australian Melanoma Health Study.

BACKGROUND: Breslow thickness is the most important predictor of survival in localized malignant melanoma. A number of melanoma risk factors have been shown to be associated with Breslow thickness; however, the role of genetic loci has been little investigated to date. OBJECTIVES: To investigate the association of known melanoma susceptibility genetic loci with Breslow thickness. METHODS: Participants were 800 individuals from the Western Australian Melanoma Health Study who completed a questionnaire and provided a DNA sample. Genetic association analyses between single-nucleotide polymorphisms (SNPs) from 15 candidate melanoma susceptibility genes and Breslow thickness were performed, controlling for relevant covariates. RESULTS: Older age at diagnosis and absence of naevi were associated with increased Breslow thickness. Following adjustment for multiple testing, no SNPs were significantly associated with Breslow thickness. CONCLUSIONS: Associations observed between Breslow thickness and age and naevi reinforce current knowledge. Some evidence of shared genetic determinants between melanoma risk and Breslow thickness was found. Further studies are required to confirm this finding.

The aggregation of early-onset melanoma in young Western Australian families.

BACKGROUND: Few studies have examined the familial aggregation of melanoma or its co-aggregation with other cancers using whole-population based designs. This study aimed to investigate aggregation patterns in young Western Australian families, using population-based linked health data to identify individuals born in Western Australia between 1974 and 2007, their known relatives, and all incident cancer diagnoses within the resulting 1,506,961 individuals. METHODS: Cox proportional hazards regression models were used to compare the risk of melanoma for first-degree relatives of melanoma cases to that for first-degree relatives of controls, with bootstrapping used to account for correlations within families. The risk of (i) developing melanoma based on the number of first-degree relatives with other cancers, and (ii) developing non-melanoma cancers based on the number of first-degree relatives diagnosed with melanoma was also investigated. RESULTS: First-degree relatives of melanoma cases had a significantly greater incidence of melanoma than first-degree relatives of individuals not affected with melanoma (Hazard Ratio (HR)=3.58, 95% bootstrap confidence interval (CI): 2.43-5.43). Sensitivity analyses produced a higher hazard ratio estimate when restricted to melanoma cases diagnosed before 40 years of age (HR=3.77, bootstrap 95% CI: 2.49-6.39) and a lower estimate when only later-onset cases (>40 years) were considered (HR=2.45, bootstrap 95% CI: 1.23-4.82). No significant evidence was found for co-aggregation between melanoma and any other cancers. CONCLUSIONS: Results indicated a strong familial basis of melanoma, with the higher than expected hazard ratio observed likely to reflect early-age at onset cases in this young cohort, supported by the results of the sensitivity analyses. Exploratory analyses suggested that the determinants of melanoma causing the observed aggregation within families may be independent of other malignancies, although these analyses were limited by the young age of the sample. Determining familial aggregation patterns will provide valuable knowledge regarding improved clinical risk prediction and the underlying biological mechanisms of melanoma and other cancers.