title: Patterns of metastases in familial and non-familial melanoma.
abstract: Family history is a strong risk factor for the development of primary melanoma and is associated in a subset with inherited mutations in melanoma susceptibility genes. This study sought to determine whether differences in metastatic pattern exist between patients with a positive family history (FH+) and those with a negative family history (FH-). Such differences could have importance for clinical management and in the determination of the function of both known and putative melanoma susceptibility genes. A retrospective, nested case-controlled study was performed. Of the FH+ cohort (n = 38), 26 were from kindreds with two histologically verified affected first-degree relatives and 12 were from kindreds with three or more affected members, at least two of whom were first-degree relatives. Three FH- controls from the Sydney Melanoma Unit database were matched to each case for age, sex, stage at diagnosis, number of primary melanomas and year of diagnosis (n = 114). There were no statistically significant differences between the two groups with regard to overall survival from initial diagnosis (FH+, 57.4 months; FH-, 50.0 months; P = 0.99), median survival from time of first metastasis (FH+, 15.4 months; FH-, 15.9 months; P = 0.94), or median disease-free interval (FH+, 26.4 months; FH-, 29.7 months; P = 0.73). On multivariate conditional logistic regression analysis, there was no statistically significant difference between the two groups in the probability of developing initial metastases or of ever developing metastases at specific sites. Survival, disease-free interval and distribution of metastatic sites are similar in both familial and non-familial melanoma. Genetic susceptibility for melanoma may lower the threshold for entering an otherwise common molecular pathway for tumour development and evolution.
authors.affiliation: Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, NSW 2145, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Hornbuckle
authors.forename: Gordana
authors.initials: G
authors.lastname: Culjak
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jarvis
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.forename: Alan
authors.initials: A
authors.lastname: Coates
authors.forename: Graham
authors.initials: G
authors.lastname: Mann
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008297:Male; D008403:Mass Screening; D008545:Melanoma / Q000235:genetics* / Q000556:secondary*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*; D015996:Survival Rate