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.

Publication Type:

Journal Article


Blood, Volume 112, Issue 7, p.2694-702 (2008)


2008, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Agents, Demography, Female, Haplotypes, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Multivariate Analysis, Polymorphism, Single Nucleotide, Proportional Hazards Models, Public Health Sciences Division, ROC Curve, Survival Analysis, Time Factors, United States


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.