Abstract
Background The influence of HLA class I and II loci on the susceptibility to melanoma remains an area of intense debate. This study aimed to examine whether the HLA system was related to melanoma susceptibility and prognosis in a southern Spanish population. Methods In this study, HLA class I and class II genotyping were performed using polymerase chain reaction sequence-specific oligonucleotides (PCR-SSO) in 237 Spanish melanoma patients and 636 ethnically matched controls. Data were analyzed according to the clinical characteristics of the defined subgroups. Results Compared to the control group, DRB1∗16:01 (4% vs. 1.3%, p=0.001, Pc = 0.035, OR = 3.28) and DQB1∗05:02 (4.9% vs. 2%, p=0.001, Pc = 0.017, OR = 2.54) were positivity associated with the susceptibility to melanoma. Both DRB1∗16:01 (5.4% vs. 1.3%, p=0.001, Pc = 0.035, OR = 4.46) and DQB1∗05:02 (6.5% vs. 2%, p=0.001, Pc = 0.017, OR = 3.44) also showed a positive correlation with Breslow thickness >1.5 mm, most notably at an early age of diagnosis (≤58 years), DRB1∗16:01 (4.2% vs. 1.3%, p=0.001, Pc = 0.035, OR = 3.41) and DQB1∗05:02 (5.4% vs. 2%, p=0.002, Pc = 0.034, OR = 2.86). Conclusion These findings established HLA-DRB1∗16:01 and HLA-DQB1∗05:02 loci as melanoma risk factors in the southern Spanish population.
Highlights
Malignant melanoma is characterized by a variable clinical outcome due to the complex interactions of human leukocyte antigens (HLAs), antigen-specific cytolytic T cells (CTLs), and natural killer (NK) cells [1,2,3]
No significant differences in the frequency of HLA-A, -B, and -C alleles were observed between groups, some were of higher number in melanoma patients compared with healthy controls (HLA-A ∗ 02:05: 3% vs. 1.1%, p 0.006, Pc 0.18, and HLA-B ∗ 35:03: 3.6% vs. 1.5%, p 0.006, Pc 0.29)
To study the differences in the frequency of HLA alleles according to the melanoma type, 154 cases of superficial spreading melanoma (SSM), 54 cases of nodular melanoma (NM), 19 cases of lentigo maligna melanoma (LMM), and 10 cases of acral lentiginous melanoma (ALM) were compared
Summary
Malignant melanoma is characterized by a variable clinical outcome due to the complex interactions of human leukocyte antigens (HLAs), antigen-specific cytolytic T cells (CTLs), and natural killer (NK) cells [1,2,3]. HLA class I molecules participate in tumor cell recognition for CD8+ T-cell-mediated clearance [4, 5], whilst HLA class II molecules stimulate CD4+ T cells to combat melanoma progression [6]. It is, speculated that the susceptibility to melanoma is closely associated with specific HLA genes [7]. Schachter et al reported an increase in the frequency of HLA-A24, -A26, and -B38 antigens in Jewish melanoma patients compared with control cases [9].
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