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

Thomas Matthew Habermann, Sophia S. Wang, Matthew J. Maurer, Lindsay M. Morton, Charles F. Lynch, Stephen Maxted Ansell, Patricia Hartge, Richard K. Severson, Nathaniel Rothman, Scott Davis, Susan M. Geyer, Wendy Cozen, Stephen J. Chanock, James R Cerhan

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Abstract

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 populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P=.03) and SNPs in IL8RB (rs1126580; HR ag/gg=2.11; Cl, 1.28-3.50), IL1A (rs1800587; HR CT/TT=1-90; Cl, 1.26-2.87), TNF (rs1800629; HR AG/GG=1. 44; Cl, 0.95-2.18), and IL4R (rs2107356; HR cc/ct=1.97; Cl, 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 × 10 -11). Kaplan-Meier 5-year survival estimates for low, intermediatelow, 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.

Original languageEnglish (US)
Pages (from-to)2694-2702
Number of pages9
JournalBlood
Volume112
Issue number7
DOIs
StatePublished - Oct 1 2008

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Lymphoma, Large B-Cell, Diffuse
Polymorphism
Hazards
Genes
Cells
Demography
Nucleotides
Survival
Single Nucleotide Polymorphism
Germ Cells
Interleukin-10
Rituximab
Proportional Hazards Models
Haplotypes
Confidence Intervals

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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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. / Habermann, Thomas Matthew; Wang, Sophia S.; Maurer, Matthew J.; Morton, Lindsay M.; Lynch, Charles F.; Ansell, Stephen Maxted; Hartge, Patricia; Severson, Richard K.; Rothman, Nathaniel; Davis, Scott; Geyer, Susan M.; Cozen, Wendy; Chanock, Stephen J.; Cerhan, James R.

In: Blood, Vol. 112, No. 7, 01.10.2008, p. 2694-2702.

Research output: Contribution to journalArticle

Habermann, Thomas Matthew ; Wang, Sophia S. ; Maurer, Matthew J. ; Morton, Lindsay M. ; Lynch, Charles F. ; Ansell, Stephen Maxted ; Hartge, Patricia ; Severson, Richard K. ; Rothman, Nathaniel ; Davis, Scott ; Geyer, Susan M. ; Cozen, Wendy ; Chanock, Stephen J. ; Cerhan, James R. / 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. In: Blood. 2008 ; Vol. 112, No. 7. pp. 2694-2702.
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abstract = "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 populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P=.03) and SNPs in IL8RB (rs1126580; HR ag/gg=2.11; Cl, 1.28-3.50), IL1A (rs1800587; HR CT/TT=1-90; Cl, 1.26-2.87), TNF (rs1800629; HR AG/GG=1. 44; Cl, 0.95-2.18), and IL4R (rs2107356; HR cc/ct=1.97; Cl, 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 × 10 -11). Kaplan-Meier 5-year survival estimates for low, intermediatelow, 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.",
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T1 - 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

AU - Habermann, Thomas Matthew

AU - Wang, Sophia S.

AU - Maurer, Matthew J.

AU - Morton, Lindsay M.

AU - Lynch, Charles F.

AU - Ansell, Stephen Maxted

AU - Hartge, Patricia

AU - Severson, Richard K.

AU - Rothman, Nathaniel

AU - Davis, Scott

AU - Geyer, Susan M.

AU - Cozen, Wendy

AU - Chanock, Stephen J.

AU - Cerhan, James R

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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 populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P=.03) and SNPs in IL8RB (rs1126580; HR ag/gg=2.11; Cl, 1.28-3.50), IL1A (rs1800587; HR CT/TT=1-90; Cl, 1.26-2.87), TNF (rs1800629; HR AG/GG=1. 44; Cl, 0.95-2.18), and IL4R (rs2107356; HR cc/ct=1.97; Cl, 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 × 10 -11). Kaplan-Meier 5-year survival estimates for low, intermediatelow, 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.

AB - 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 populationbased estimates conditioned on surviving 12 months. An IL10 haplotype (global P=.03) and SNPs in IL8RB (rs1126580; HR ag/gg=2.11; Cl, 1.28-3.50), IL1A (rs1800587; HR CT/TT=1-90; Cl, 1.26-2.87), TNF (rs1800629; HR AG/GG=1. 44; Cl, 0.95-2.18), and IL4R (rs2107356; HR cc/ct=1.97; Cl, 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 × 10 -11). Kaplan-Meier 5-year survival estimates for low, intermediatelow, 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.

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