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

Abstract

Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.

HLA-DQA1 and -DQB1 allele typing in southern Taiwanese women with breast cancer

“…Previous studies have indeed shown that certain HLA class II genes may affect the risk of certain cancers (12)(13)(14)(15)(16)(17)(18)(19). The HLA system also plays a pivotal role in mounting and recruiting of cytotoxic T-lymphocytes against tumor antigens that may contribute to tumor invasion via destructive immune responses.…”

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

“…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. 94 Other studies have shown associations between CMM and additional HLA alleles. Negative associations were found between DQB1*0302/0303 and CMM, whereas a positive association was found for DQB1*0501 in two Italian studies.…”

“…97 A study among the Spanish population indicated that the contribution of HLA class II alleles to CMM susceptibility was not significant, but did report a statistically significant increase in HLA-DQA1 homozygosity among CMM patients versus controls and a significant association between HLA-DQB1*0301 and red or fair-haired persons (relative risk, 5.65). 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.…”

“…91 The association between human leukocyte antigen (HLA) class II loci and CMM is a topic of widespread debate as it has been postulated that this relationship might be the immunogenetic basis for melanoma susceptibility. 94,95 In an early study of 45 Caucasian patients with CMM, Lee et al reported that 56% carried the HLA class II allele, DQB1*0301, versus only 27% of Caucasian controls (P = .003); additionally, the allele was associated with advanced disease at diagnosis, with 44% of the DQB1*0301-positive patients presenting with metastases compared with only 5% of DQB1*0301-negative patients (P = 0.003) (see Table II). 96 Another study by these same authors found that stage I or II CMM patients who carried the HLA-DQB1*0301 allele were at an increased risk of developing recurrent disease compared with stage-matched patients who were DQB1*0301-negative (see Table II).…”

Gene expression signatures and ex vivo drug sensitivity profiles in children with acute lymphoblastic leukemia

“…PIP4K2A and other phosphoinositide lipid kinases are highly mutated in colon, brain, and gastric cancers, where apparent gain-of-function mutations are related to increased activity for this family of lipid kinases (Bachman et al 2004;Samuels et al 2004;Ikenoue et al 2005;Samuels and Ericson 2006). Decrease or lack of expression of HLA-DQA1 gene affects the proliferation and progression of such tumors as gastric cancer, melanoma, and lymphoma (Riemersma et al 2000;Garza-González et al 2004;Planelles et al 2006). Lack of HLA-DQA1 expression at the surface of tumor cells prevents these cells from CD4+ and CD8+ lymphocytes cytotoxic effect.…”