Preliminary characterization of MHC polymorphisms as risk factors for pediatric and adult classical Hodgkin lymphoma in a region with early EBV seroconversion

HASSAN, R.; GARCIA A; COHEN, M; VERA LOZADA G; OLIVEIRA SILVA M; SEGGES P; GANTUZ, M; DE MATTEO, E; MAGALHÃES BARROS, M; PRECIADO, M. V.; PAOLA ANDREA CHABAY

Colonia

Simposio; 9th International Symposium on Hodgkin Lymphoma; 2013

German Hodgkin Study Group

Genetic factors linked to the Major Histocompatibility Complex (MHC) have been associated to the risk of classical Hodgkin lymphoma (cHL) in distinct epidemiological frameworks (i.e. developed countries, EBV late seroconversion, adults). This is a pilot study aiming to explore the role of MHC genetic variants in the risk of cHL in developing countries where early EBV seronversion is the rule. A group of 84 children and adolescents (3-18 years, median 11; M:F 2.45) and 67 adults (19-82 years, median 32; M:F 1.7) with cHL, and 67 reactive hyperplasia (2-48 years, M:F 1.2) were included, from cases diagnosed in Brazil and Argentina public Hospitals. EBV was detected by EBER-ISH and PCR. In 147 cases, HLAs A/B/DRB were genotyped using the LabType®SSO typing test (Luminex). HLA-linked SNPs (rs6457110, rs2530388, rs6903608, and rs2523969) were genotyped using TaqMan® probes. NS subtype was detected in 46% children and 68% adults, followed by MC (41% vs 14%). EBV was detected in 64% of pediatric cHL, 54.5% of adult cHL and 39% controls. The more frequent HLA alleles were HLA-A*02 (43%), HLA-B*44 (14%) and HLA-DRB*13 (28%), without differences between cases and controls, regardless of EBV status. DR3 and DR8 alleles were preferentially associated with EBV+ cHL females (38.5% vs 6.4% males; p=0.017; p=0.003). Case-control comparison for rs6457110 disclosed no significant associations. When compared EBV+ and EBV- cHL stratified by sex, the A allele/AA genotype were more frequent in male EBV+ cases (27% vs 5% female, p=0.02). For SNP rs2330388, no differences were found between cases and controls. A allele/AA genotype were associated with EBV+ cHL male children (p=0.018). For SNPrs6903608, genotypic frequencies were significantly different in cases and controls (CC 20% vs 6%; p= 0.016), more marked in the EBV-negative cases. In sum, no direct associations were demonstrated between HLA-A*01 or HLA-A*02 and risk of cHL in this region. However, a complex interaction was found among specific alleles of HLA and SNPs in respect of sex, age, and EBV, which demands, besides in=creasing sample size, specific experimental designs to disclose age- and sex-associated risks in this region with early EBV seroconversion.