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.
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.
Habermann
Thomas M
TM
Mayo Clinic College of Medicine, Rochester, MN, USA.
Wang
Sophia S
SS
Maurer
Matthew J
MJ
Morton
Lindsay M
LM
Lynch
Charles F
CF
Ansell
Stephen M
SM
Hartge
Patricia
P
Severson
Richard K
RK
Rothman
Nathaniel
N
Davis
Scott
S
Geyer
Susan M
SM
Cozen
Wendy
W
Chanock
Stephen J
SJ
Cerhan
James R
JR
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003710:Demography; D005260:Female; D006239:Haplotypes; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology*; D016016:Proportional Hazards Models; D012372:ROC Curve; D000069283:Rituximab; D016019:Survival Analysis; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab