Patterns of familial aggregation of three melanoma risk factors: great number of naevi, light phototype and high degree of sun exposure

Background Besides melanoma susceptibility genes and shared environmental e xposures, part of the familial clustering of cutaneous malignant melanoma ( CMM) might be due to familial aggregation of melanoma-associated phenotypes . Our goal was to assess the patterns of familial aggregation of three mela noma risk factors: great number of naevi (GNN), light phototype (LP) and hi gh degree of sun exposure (HDSE). Methods Familial aggregation of GNN, LP and HDSE was investigated in 66 Fre nch families with at least two CMM cases and was measured by the asssociati on of the relatives' traits with the probands' traits, using the generalize d estimating equations approach. The probands were the melanoma cases leadi ng to ascertainment of the families, subdivided into cases (with the trait studied) and controls (without the trait). Results We found significant evidence for familial aggregation of GNN only among sibs (OR = 3.7, 95% CI : 1.4-10.5, P = 0.01), of LP among blood relat ives (OR = 3.8, 95% CI : 1.8-8.0, P = 0.004) and of HDSE among blood relati ves (OR = 4.5, 95% CI : 2.1-9.9, P < 0.001) and spouses (OR = 44.3, 95% CI : 5.1-382.2, P < 10(-3)). These results suggest that genetic factors might account for the clustering of GNN and LP and shared environment for the agg regation of HDSE. The GNN clustering was lower in families with increasing numbers of CMM (greater than or equal to 3 cases) or presence of p16 mutati ons, the opposite being observed for LP and HDSE. Moreover, the familial ag gregation of LP was significantly lower in families with highly sun-exposed members. Conclusion Melanoma might not only result from specific genetic and environ mental factors but also from those underlying melanoma-associated traits in volving complex gene-gene and gene-environment interactions.