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There is some evidence that genes at loci on the lower end of chromosome 14, encoding for the immunoglobulin heavy chains allotypes (Gm), may influence susceptibility to human tumors. We examined the Gm and Km (IgK light chain) allotype distribution in a sample of 41 patients with familial malignant melanoma and in 79 healthy relatives. An increased frequency of the haplotype carrying the Gm (2) allotype, namely Gm (1, 2, 17;..; 21), seemed to be peculiar to patients, since it was almost twice as frequent in them than in the healthy population and four times as frequent with respect to the healthy relatives. Our findings are in keeping with previous suggestions that in Caucasian melanoma patients genes of the immunoglobulin heavy chain constant region, or Gm-linked genes, may enhance susceptibility to malignant melanoma.

One hundred and twenty-four subjects belonging to 25 families, 51 with familial malignant melanoma (FMM), and 186 subjects belonging to 41 families, 41 with sporadic malignant melanoma, were typed for the HLA A, B, C and DR loci of the HLA system. There was the same statistically significant difference in the frequency of the haplotype A9, B35, Cw4 between each group of patients and the respective healthy relatives (p = 0.01, p = 0.01 and p = 4 × 10−3, respectively). Moreover, the higher frequency of the haplotype A9, B35, Cw4 in the healthy members of the FMM families (42.46 %) compared with the healthy members of the SMM families (23.44 %) indicates that in the latter group other individuals are at risk for the disease. Furthermore, the different frequency of haplotypes B5, DR5 and B5, Cw1 suggests that differences exist between the two groups of healthy relatives. These observations confirm that the HLA region is involved in the etiology of malignant melanoma.