title: Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma.
abstract: Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD 20892-7234, USA. wangso@mail.nih.gov
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Scott
authors.initials: S
authors.lastname: Davis
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Richard K
authors.initials: RK
authors.lastname: Severson
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000368:Aged; D005189:False Positive Reactions; D005260:Female; D005802:Genes, MHC Class II; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000453:epidemiology* / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D018426:SEER Program / Q000706:statistics & numerical data; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: C445323:FCGR2A protein, human; D008233:Lymphotoxin-alpha; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha