title: Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1.
abstract: Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk.
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute and City of Hope, Duarte, California, United States of America. sowang@coh.org
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Yani
authors.initials: Y
authors.lastname: Lu
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Amr M
authors.initials: AM
authors.lastname: Abdou
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Anneclaire
authors.initials: A
authors.lastname: De Roos
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morton
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016001:Confidence Intervals; D005260:Female; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains
references.citation: Blood. 2009 Feb 26;113(9):1899-905
references.pmid: 19066394
references.citation: Int J Cancer. 2009 Jul 15;125(2):398-405
references.pmid: 19365835
references.citation: Cancer Res. 2007 May 15;67(10):5042-54
references.pmid: 17510437
references.citation: Am J Epidemiol. 2010 Jul 1;172(1):58-69
references.pmid: 20562184
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):925-33
references.pmid: 15824165
references.citation: Lancet Oncol. 2006 Jan;7(1):27-38
references.pmid: 16389181
references.citation: Blood. 2008 Dec 15;112(13):5150-60
references.pmid: 18796628
references.citation: Clin Gastroenterol Hepatol. 2008 Apr;6(4):451-8
references.pmid: 18387498
references.citation: Cancer Causes Control. 2007 Nov;18(9):989-99
references.pmid: 17653830
references.citation: Lancet Oncol. 2005 Jul;6(7):469-76
references.pmid: 15992695
references.citation: Autoimmun Rev. 2002 Feb;1(1-2):29-35
references.pmid: 12849055
references.citation: J Hum Genet. 2009 Jan;54(1):15-39
references.pmid: 19158813
references.citation: Am J Epidemiol. 2010 Feb 1;171(3):267-76
references.pmid: 20047977
references.citation: Blood. 2008 Apr 15;111(8):4029-38
references.pmid: 18263783
references.citation: Cancer Res. 2006 Oct 1;66(19):9771-80
references.pmid: 17018637
references.citation: Nat Genet. 2010 Aug;42(8):661-4
references.pmid: 20639881
references.citation: Blood. 2007 Apr 15;109(8):3479-88
references.pmid: 17185468
references.citation: Int J Cancer. 2008 Jan 1;122(1):144-54
references.pmid: 17708556
references.citation: Leukemia. 2010 May;24(5):1055-8
references.pmid: 20147981
references.citation: Epidemiology. 2005 Jul;16(4):516-25
references.pmid: 15951670
references.citation: Cancer Causes Control. 2009 Oct;20(8):1291-302
references.pmid: 19396635
references.citation: Ground Water. 2003 May-Jun;41(3):316-20
references.pmid: 12772824
references.citation: Int J Cancer. 2008 May 1;122(9):2062-70
references.pmid: 18167059
references.citation: Cancer Res. 2005 Dec 1;65(23):11214-26
references.pmid: 16322272