Available data have led to a controversy on the relationship between
human leukocyte antigen (HLA) and
cutaneous malignant melanoma susceptibility or prognosis. Moreover, the influence of
HLA-C on
melanoma has not yet been well established. Therefore, the aim of the current study was to analyze the possible influence of the HLA system on
melanoma susceptibility and prognosis in the Spanish population. For this purpose,
HLA-A and
HLA-B serotyping and
HLA-C,
HLA-DRB1, and
HLA-DQB1 genotyping by polymerase chain reactions using sequence-specific
oligonucleotide (PCR-SSO) and sequence-specific primer (PCR-SSP) were performed in 174
melanoma patients and 227 ethnically matched controls. The number of controls was increased up to 356 for
HLA-C typing. Patients were stratified according to the histological subtypes of
melanoma, sentinel lymph node status,
tumor thickness, and ulceration of primary lesion. No
HLA-A,
HLA-B,
HLA-DRB1, or
HLA-DQB1 relationship with
melanoma was observed for susceptibility or disease prognosis. However, the analysis of
HLA-C locus showed that individuals homozygous for HLA-C(Lys80) were significantly more frequent within the patient than the control group. Remarkably, individuals homozygous for group 2
HLA-C alleles (HLA-C(Lys80)) seem to be associated with metastatic progression of
melanoma. In contrast, we found a negative association between group 1
HLA-C alleles (HLA-C(Asn80)) and
disease susceptibility or
metastasis development. In conclusion, although an association with
HLA-A,
HLA-B,
HLA-DRB1, or
HLA-DQB1 was not demonstrated, the study of the
HLA-C locus revealed that the analysis of the dimorphism at position 80 in the alpha1 helix may help to evaluate the risk and prognosis of
melanoma in our population.