title: The aggregation of early-onset melanoma in young Western Australian families.
abstract: 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.
authors.affiliation: Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia. Electronic address: sarah.ward@uwa.edu.au.
authors.forename: S V
authors.initials: SV
authors.lastname: Ward
authors.affiliation: Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: J G
authors.initials: JG
authors.lastname: Dowty
authors.affiliation: Laboratory for Cancer Medicine, Harry Perkins Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: R J
authors.initials: RJ
authors.lastname: Webster
authors.affiliation: Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Cadby
authors.affiliation: Telethon Kids Institute, Subiaco, Western Australia, Australia.
authors.forename: E J
authors.initials: EJ
authors.lastname: Glasson
authors.affiliation: School of Population Health, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: J S
authors.initials: JS
authors.lastname: Heyworth
authors.affiliation: Department of General Practice, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Emery
authors.affiliation: St John of God Dermatology, St John of God Health Care, Subiaco, Perth, Western Australia, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Cole
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Millward
authors.affiliation: Burn Injury Research Unit, The University of Western Australia, Crawley, Western Australia, Australia; Fiona Wood Foundation, Telstra Burns Reconstruction and Rehabilitation Unit, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: F M
authors.initials: FM
authors.lastname: Wood
authors.affiliation: Joanna Briggs Institute and School of Translational Health Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: L J
authors.initials: LJ
authors.lastname: Palmer
mesh_terms: D000328:Adult; D017668:Age of Onset; D001315:Australia / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D014904:Western Australia / Q000453:epidemiology
keywords: Cancer; Cox proportional hazards model; Data linkage; Hereditary cancer syndromes; Melanoma