title: HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk.
abstract: The human leukocyte antigen (HLA) genes are candidate genetic susceptibility loci for childhood acute lymphoblastic leukemia (ALL). We examined the effect of HLA-DP genetic variation on risk and evaluated its potential interaction with 4 proxies for early immune modulation, including measures of infectious exposures in infancy (presence of older siblings, daycare attendance, ear infections) and breastfeeding. A total of 585 ALL cases and 848 controls were genotyped at the HLA-DPA1 and DPB1 loci. Because of potential heterogeneity in effect by race/ethnicity, we included only non-Hispanic white (47%) and Hispanic (53%) children and considered these 2 groups separately in the analysis. Logistic regression analyses showed an increased risk of ALL associated with HLA-DPB1*01:01 (odds ratio [OR] = 1.43, 95% CI, 1.01-2.04) with no heterogeneity by Hispanic ethnicity (P = .969). Analyses of DPB1 supertypes showed a marked childhood ALL association with DP1, particularly for high-hyperdiploid ALL (OR = 1.83; 95% CI, 1.20-2.78). Evidence of interaction was found between DP1 and older sibling (P = .036), and between DP1 and breastfeeding (P = .094), with both showing statistically significant DP1 associations within the lower exposure categories only. These findings support an immune mechanism in the etiology of childhood ALL involving the HLA-DPB1 gene in the context of an insufficiently modulated immune system.
authors.affiliation: School of Public Health, University of California, Berkeley, CA 94704, USA. kurayama@luke.or.jp
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Urayama
authors.forename: Anand P
authors.initials: AP
authors.lastname: Chokkalingam
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ma
authors.forename: Steve
authors.initials: S
authors.lastname: Selvin
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Wiemels
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.forename: Malcolm
authors.initials: M
authors.lastname: Taylor
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Gary V
authors.initials: GV
authors.lastname: Dahl
authors.forename: Priscilla
authors.initials: P
authors.lastname: Moonsamy
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trachtenberg
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Buffler
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D059867:HLA-DP alpha-Chains / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000209:etiology*; D011379:Prognosis; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D007155:Immunologic Factors