Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma

Abstract

IMPORTANCEStudies focusing on genetic susceptibility of childhood Hodgkin lymphoma (HL) are limited. OBJECTIVES To identify genetic variants associated with childhood-onset HL vs adult-onset HL. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was performed with 3 cohorts: the St Jude Lifetime Cohort Study (SJLIFE), initiated in 2007 with ongoing follow-up, and the original and expansion cohorts of the Childhood Cancer Survivor Study (CCSS), initiated in the 1990s with ongoing follow-up. Results of these genome-wide association studies (GWASs) were combined via meta-analysis. Data were analyzed from June 2021 to June 2022. MAIN OUTCOMES AND MEASURES Childhood HL was the focused outcome. Single-nucleotide variant (SNV, formerly single-nucleotide polymorphism) array genotyping and imputation were conducted for the CCSS original cohort, and whole-genome sequencing was performed for the SJLIFE and CCSS expansion cohort.RESULTS A total of 1286 HL cases (mean diagnosis [SD] age, 14.6 [3.9] years), 6193 non-HL childhood cancer cases, and 369 noncancer controls, all of European ancestry, were included in the analysis. Using step-wise conditional logistic regression, the odds ratios (ORs) for each of the 3 independent SNVs identified in the human leukocyte antigen (HLA) locus were 1.80 (95% CI, 1.59-2.03;

Expression of specific HLA class II alleles is associated with an increased risk for active tuberculosis and a distinct gene expression profile

“…Interestingly, DPB1 * 04:02 and DPB1 * 105:01 have an identical exon 2 which is encoding for the antigen recognition site in the MHC molecule and differ only by a single nucleotide in exon 3 7 . Single‐nucleotide variants within HLA have been associated with various diseases in a number of studies 31–34 . However, future studies in other populations should investigate whether the observation in this study is a coincidence of the high frequency of expression of DPB1 * 105:01 in South Africa or whether this translates to other aspects of the immunity against Mtb .…”

“…7 Singlenucleotide variants within HLA have been associated with various diseases in a number of studies. [31][32][33][34] However, future studies in other populations should investigate whether the observation in this study is a coincidence of the high frequency of expression of DPB1*105:01 in South Africa or whether this translates to other aspects of the immunity against Mtb.…”

The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

“…Leukocytes of peripheral blood or bone marrow were collected from the participants involved in our study. For the same patient, the DNA and RNA were extracted from the same type of biological sample 59–62 . Genomic DNA was isolated by standard methods according to the manufacturer's instruction of TIANamp blood DNA kit (Tiangen Biotech).…”

“…For the same patient, the DNA and RNA were extracted from the same type of biological sample. [59][60][61][62] Genomic DNA was isolated by standard methods according to the manufacturer's instruction of TIANamp blood DNA kit (Tiangen Biotech). The quality and concentration of DNA were determined using a DeNovix DS-11 Spectrophotometer (DeNovix Inc.).…”

Classic Hodgkin Lymphoma in Adolescents and Young Adults

“…Genome-wide association studies investigating the genetic etiology of HL suggest common associations in HLA loci across the full age spectrum, although a novel non-HLA locus has been identified supporting a putative role of NF-kB activation in HL pathogenesis, particularly in HL developing in children and AYAs. 6 Recently, whole-genome sequencing of families with at least two first-degree relatives with HL demonstrated recurrent predisposing variants in several loci; these require validation but provide further evidence of germline predisposition in a subset of patients. 7 BIOLOGY HL is characterized by two main types, the more commonly diagnosed classic HL (cHL) and the rare nodular lymphocyte predominant HL, not the purview of this review.…”