SummaryIn this study we analyzed the human leukocyte antigen (HLA) pattern of North American Caucasian patients with metastatic melanoma as compared with the North American Caucasian (NAC) population. We also investigated whether the HLA type of melanoma patients had an effect on their tolerance and response to interleukin-2 (IL-2)-based therapy. Four hundred twelve serologic phenotypes of Caucasian melanoma patients referred to the National Cancer Institute, National Institutes of Health, from February 1989 through December 1993 were collected by typing the patient's peripheral blood lymphocytes. Furthermore, 74 melanoma patients were typed for HLA class II by high-resolution sequence specific primer-polymerase chain reaction. Response rate and treatment-related toxicity in those patients receiving IL-2-based treatment (N = 272) were compared with HLA serologic types. The frequency of four HLA-B alleles was significantly different in the melanoma compared with the NAC population: Of these, HLA-B5, -B8, and -B15 had a frequency falling between the NAC and the Northern European population. No other significant differences between melanoma patients and NAC population were noted for other HLA loci. A correlation was noted between HLA-DR3 and -DR4 alleles and decreased tolerance to IL-2, whereas homozygosity for HLA-DR decreased the chance of response. There were no significant associations between HLA type and response. It is unlikely that the associations noted between some HLA-B alleles and melanoma bear significantly on the etiology of the disease. The differences seen between American melanoma patients and the NAC population are probably best explained by geographical ancestry. The association between HLA-DR and tolerance to IL-2 therapy noted in this study may offer insight toward the understanding of mechanisms regulating the cascade of events after the systemic administration of IL-2.
Keywords
HLA; Malignant melanoma; NAC patientsSeveral associations between the prevalence pattern of a human leukocyte antigen (HLA) and a pathologic condition have been reported (1). The recognition of an association is presumed to (a) help prevention in a population at risk, (b) define a genetic linkage between a disease and a portion of the human genome that may shed light on etiological factors, and (c) have In this study we wanted to analyze possible associations between melanoma and HLA. Associations were explored between HLA frequencies in melanoma patients compared with the North American Caucasian (NAC) population with the caveat that, because melanoma occurs more commonly in people with light complexion of northern European ancestry, some differences could be due to the different ancestral origin of melanoma patients. Specifically, we studied HLA-B5, -B7, -B8, and -B15 alleles, whose distribution varies according to latitude in Europe (6), with the a priori hypothesis that their frequency in melanoma patients would fall in between the NAC and the Northern European population. Furthermore, because an increased risk of ...