Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology

Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different NHL subtypes. Complementing these efforts, we conducted human leukocyte antigen ( HLA ) Class I and Class II genotyping among 610 non-Hodgkin lymphoma (NHL) cases and 555 controls of non-Hispanic Caucasian descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1 *0101 for follicular lymphoma (OR=2.14, p=0.0004), HLA-DRB1 *0401 for diffuse large B-cell lymphoma (DLBCL) (OR=0.45, p=0.006), and HLA-DRB1 * 13 and follicular lymphoma (OR=0.48, p=0.008). We further observed significant heterozygote advantage for HLA Class I alleles and NHL, and particularly DLBCL (p-trend=0.01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.