Familial melanoma: a meta-analysis and estimates of attributable fraction

Melanoma commonly clusters in families, and the recent identification of numerous genotypes predicting higher risks of melanoma has led to the widespread perception that this cancer is predominantly a genetic disease. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of familial factors to melanoma, estimated by the population attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and family history of the disease; we identified 22 such studies using citation databases, followed by manual review of retrieved references. We calculated summary RRs using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. Overall, family history was associated with a significant 2-fold increased risk of melanoma (odds ratio, 2.06; 95% confidence interval, 1.72-2.45); however, there was significant heterogeneity (P = 0.01). The pooled estimate for population-based studies (n = 11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013, respectively). Two studies used record linkage to verify family history in relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00) with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a positive family history ranged from 0.007 for Northern Europe to 0.064 for Australia (0.040 for all regions combined). Our findings suggest that only a small percentage of melanoma cases (always <7%) are attributable to familial risk; the majority of melanomas are presumably attributable to other factors.