Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era

Blood. 2008 Oct 1;112(7):2694-702. doi: 10.1182/blood-2007-09-111658. Epub 2008 Jul 16.


To evaluate the hypothesis that host germ line variation in immune genes is associated with overall survival in diffuse large B-cell lymphoma (DLBCL), we genotyped 73 single nucleotide polymorphisms (SNPs) from 44 candidate genes in 365 DLBCL patients diagnosed from 1998 to 2000. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of SNPs with survival after adjusting for clinical factors. During follow-up, 96 (26%) patients died, and the median follow-up was 57 months for surviving patients. The observed survival of this cohort was consistent with population-based estimates conditioned on surviving 12 months. An IL10 haplotype (global P = .03) and SNPs in IL8RB (rs1126580; HR(AG/GG) = 2.11; CI, 1.28-3.50), IL1A (rs1800587; HR(CT/TT) = 1.90; CI, 1.26-2.87), TNF (rs1800629; HR(AG/GG) = 1.44; CI, 0.95-2.18), and IL4R (rs2107356; HR(CC/CT) = 1.97; CI, 1.01-3.83) were the strongest predictors of overall survival. A risk score that combined the latter 4 SNPs with clinical factors was strongly associated with survival in a Cox model (P = 6.0 x 10(-11)). Kaplan-Meier 5-year survival estimates for low, intermediate-low, intermediate-high, and high-risk patients were 94%, 79%, 60%, and 48%, respectively. These data support a role for germ line variation in immune genes, particularly genes associated with a proinflammatory state, as predictors of late survival in DLBCL.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents / therapeutic use
  • Demography*
  • Female
  • Haplotypes
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / epidemiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Polymorphism, Single Nucleotide / immunology*
  • Proportional Hazards Models
  • ROC Curve
  • Rituximab
  • Survival Analysis
  • Time Factors
  • United States / epidemiology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Rituximab