Molecular Genetic Analysis of HLA-DR and -DQ Alleles in Spanish Patients with Melanoma

Abstract

Controversial data have been reported about HLA alleles and susceptibility to melanoma. The relationship between distribution of HLA alleles in patients with melanoma and susceptibility to tumour was analysed, to study the possible correlation between HLA class II DQA1, DQB1 and DRBI genes and melanoma in a Spanish population. Genomic DNA from 82 patients with melanoma and 367 random healthy donors, from the same geographic area, were typed by PCR-SSP (sequence specific primers). The patients were also divided into different groups according to the age and presence of cancer relatives, and compared with the controls. None of these HLA class II alleles showed significant positive or negative associations with either the overall population of patients with melanoma or the considered subgroups. Moreover, values for relative risk of DQB1*0301, DQB1*0302, DQB1*0303, DQB*05, DQA1*0401, DQA1*0101/0104 and DRB*08, which have been reported to be increased or decreased in patients with melanoma, were very low and of no statistical significance. Our results indicate that HLA class II alleles may not contribute to a strong susceptibility to melanoma in the Spanish population, although further studies on larger series are needed to corroborate this. Key words:

HLA class II polymorphisms in Spanish melanoma patients: homozygosity for HLA-DQA1 locus can be a potential melanoma risk factor

“…On the other hand, discrepancies in results reported could be due to the limited size of the patient group utilized in some of these studies. For discarding this hypothesis, we increased our population of patients examined in a previous study by 43%, in whom we did not find any HLA allele associated with melanoma 20 . However, results did not change and the prevalence of HLA class II alleles was very similar in both groups of patients (82 compared with 117 patients), with no difference with respect to controls in both studies.…”

“…For example, discrepant results have been described for DQB1*0301 in North American white patients [4][5][6][7] or for DQB1*0303 in European white patients. 9,10,20 On the other hand, discrepancies in results reported could be due to the limited size of the patient group utilized in some of these studies. For discarding this hypothesis, we increased our population of patients examined in a previous study by 43%, in whom we did not find any HLA allele associated with melanoma.…”

“…However, we do not believe that racial HLA polymorphisms explain controversial data in the case of melanoma, because different results have been reported for the same allele even into the same ethnic group. For example, discrepant results have been described for DQB1*0301 in North American white patients 4–7 or for DQB1*0303 in European white patients 9,10 , 20 …”

“…7 We recently reported the frequencies of HLA-DRB1, -DQA1 and -DQB1 alleles as defined by polymerase chain reaction with sequence-specific primers (PCR-SSP) in a group of 82 Spanish melanoma patients; no significant differences were found between patients and controls. 20 In the present study we have reanalysed the HLA pattern in a larger group of patients with melanoma, stratified according to different clinicopathological factors. We have particularly focused on HLA-DQB1*0301-positive and -negative subgroups with regard to these factors.…”

“…Thus, DQB1*0301 has been found positively [4][5][6]8 as well as negatively associated 9 and even not associated with melanoma at all. 7,20 Frequencies of DQB1*0302 and DQB1*0303 have been reported to be increased 10,11 or decreased 9 or not changed 20 in patients with melanoma with respect to controls.…”