Abstract
Background
Evidence is emerging that melanoma has distinct etiologic pathways and subtypes, characterized by factors like anatomic site. For example, older men have more head and neck melanomas, and younger women more leg melanomas. Family history is a strong risk factor and familial risk genes have been identified. We therefore aimed to investigate familial aggregation of melanoma from an etiologic heterogeneity perspective, to determine whether melanoma subtypes aggregate within families.
Methods
Using population-level linked health data, we examined the extent to which melanomas in first-degree relatives (FDRs) of cases shared the same body site of occurrence. FDR-pairs diagnosed with melanoma were identified using the Western Australian Cancer Registry and genealogical Family Connections System. Site was categorized as head/neck, trunk/arms, or legs. We identified 1,006 pairs of tumours from 677 family pairs and used Chi-Squared tests to evaluate familial aggregation by site. Degrees of etiologic heterogeneity of individual site-pairs were characterized by site concordance odds ratios.
Results
Familial aggregation by site was statistically significant (P = 0.01). However, only the site pairings of head/neck versus trunk/arms showed strong evidence of familial concordance (OR = 1.7, 95% CI 1.1-1.7). Trends were broadly similar in same-sex pairs.
Conclusions
Results show modest evidence of familial aggregation of melanoma by site, with overall evidence of aggregation but inconsistent patterns between sites.
Key messages
Strong etiologic differences in incidence between anatomic sites for age and sex may be more strongly influenced by non-genetic factors, such as familial patterns of sun exposure.