Molecular Analysis of HLA DRB1 and DQB 1 Polymorphism in Italian Melanoma Patients

Abstract

Several studies have reported association between a variety of malignancies and human leukocyte antigens (HLA) genes. However, conflicting data have been reported on HLA association and melanoma. We report here serologic and molecular analysis by polymerase chain reaction sequence-specific primers (PCR-SSP) and PCR sequence-specific oligonucleotides (PCR-SSO) of HLA class I1 DRBl and DQB 1 loci in 132 patients with melanoma and 102 ethnically matched controls. Molecular typing of DQB 1 polymorphism showed a significant increase of DQB 1 *050 1 (25.0% versus 14.7%; p = 0.038). Moreover, an increase of DQB1*0301, which was present in 62.8% of patients and 54.9% of controls (p = 0.136), was noted. Because DQBl*O501 and DQB 1 *0301 are strongly linked to DRB 1 *O 1 and DRB 1 * 1 1, respectively, both found increased in patients with melanoma, to look for a more stringent association with a particular allele specificity of the DR locus, we performed PCR-SSP highresolution typing of DRl and DRI 1 positive subjects. Results showed no significant difference between the frequencies of the alleles found in patients with respect to controls. Analysis of the distribution of DQB 1 *0501 and DQB 1*0301 according to the AJCC clinical stage of the disease showed no significant difference in the frequency of these alleles between the localized and the metastatic form of the disease. However, none of the HLA class I1 alleles showed significant association after correction of the p value. These results indicate that HLA class I1 alleles may not contribute to a strong susceptibility to melanoma, at least in Italian patients.

Germline melanoma susceptibility and prognostic genes: A review of the literature

“…Negative associations were found between DQB1*0302/0303 and CMM, whereas a positive association was found for DQB1*0501 in two Italian studies. 99,100 In Japanese patients with CMM, a positive association was found with DQB1*0302, whereas negative associations were reported for DRB1*0802 and DQA1*0101/ 0104/0401. 101 Finally, in a British population, an increase in the frequency of DQB1*0303 was found among CMM patients.…”

“…94 A variety of other studies have reported even more conflicting results with HLA-DQB1*0301 among CMM populations. One study reported no association between DQB1*0301 and risk of CMM, 98 whereas another found a slight, but not significant, positive association with susceptibility, 99 and yet another indicated a negative association with risk of CMM. 100 The variability of these results could, in part, be due to sample size, patient series heterogeneity, control populations, or technical differences in detecting HLA genotype.…”

HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma

“…However, conflicting data have been reported on HLA association and melanoma (1)(2)(3)(4)(5)(6)(7)(8). The presence of DQB1*0301 (1, 2) and DRB1*1101 (3) has been reported to be associated with the progression of the disease in Caucasians, and it has been reported that HLA-DQB1*0303 and DQB1*0301 can influence susceptibility and prognosis in British patients with melanoma (4).…”

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

“…Over the last three decades, several studies have examined the involvement of the HLA system in the aetiology of malignant melanoma, 1–11 and it has been speculated that HLA class II association might be the immunogenetic basis for melanoma susceptibility 1 . However, reports have not shown consistent results perhaps because of sample size, patient series heterogeneity, the choice of control populations and differences in the techniques employed for the detection of HLA antigens or alleles.…”