Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival

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

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Abstract

Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT = 2.14, 1.26-3.63), IL2 (rs2069762; HRGT/TT = 1.80, 1.06-3.05), IL12B (rs3212227; HR AC/CC = 1.83, 1.06-3.06), and IL1RN (rs454078; HRAA = 1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P = .001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P < .001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.

Original languageEnglish (US)
Pages (from-to)5439-5446
Number of pages8
JournalBlood
Volume109
Issue number12
DOIs
StatePublished - Jun 15 2007

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Follicular Lymphoma
Polymorphism
Genes
Survival
Hazards
Single Nucleotide Polymorphism
Interleukin-8
Gene expression
Interleukin-2
Demography
Kaplan-Meier Estimate
Proportional Hazards Models
Germ Cells
Genotype
Confidence Intervals
Gene Expression

ASJC Scopus subject areas

  • Hematology

Cite this

Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. / Cerhan, James R; Wang, Sophia; Maurer, Matthew J.; Ansell, Stephen Maxted; Geyer, Susan M.; Cozen, Wendy; Morton, Lindsay M.; Davis, Scott; Severson, Richard K.; Rothman, Nathaniel; Lynch, Charles F.; Wacholder, Sholom; Chanock, Stephen J.; Habermann, Thomas Matthew; Hartge, Patricia.

In: Blood, Vol. 109, No. 12, 15.06.2007, p. 5439-5446.

Research output: Contribution to journalArticle

Cerhan, JR, Wang, S, Maurer, MJ, Ansell, SM, Geyer, SM, Cozen, W, Morton, LM, Davis, S, Severson, RK, Rothman, N, Lynch, CF, Wacholder, S, Chanock, SJ, Habermann, TM & Hartge, P 2007, 'Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival', Blood, vol. 109, no. 12, pp. 5439-5446. https://doi.org/10.1182/blood-2006-11-058040
Cerhan, James R ; Wang, Sophia ; Maurer, Matthew J. ; Ansell, Stephen Maxted ; Geyer, Susan M. ; Cozen, Wendy ; Morton, Lindsay M. ; Davis, Scott ; Severson, Richard K. ; Rothman, Nathaniel ; Lynch, Charles F. ; Wacholder, Sholom ; Chanock, Stephen J. ; Habermann, Thomas Matthew ; Hartge, Patricia. / Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. In: Blood. 2007 ; Vol. 109, No. 12. pp. 5439-5446.
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AU - Wang, Sophia

AU - Maurer, Matthew J.

AU - Ansell, Stephen Maxted

AU - Geyer, Susan M.

AU - Cozen, Wendy

AU - Morton, Lindsay M.

AU - Davis, Scott

AU - Severson, Richard K.

AU - Rothman, Nathaniel

AU - Lynch, Charles F.

AU - Wacholder, Sholom

AU - Chanock, Stephen J.

AU - Habermann, Thomas Matthew

AU - Hartge, Patricia

PY - 2007/6/15

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N2 - Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT = 2.14, 1.26-3.63), IL2 (rs2069762; HRGT/TT = 1.80, 1.06-3.05), IL12B (rs3212227; HR AC/CC = 1.83, 1.06-3.06), and IL1RN (rs454078; HRAA = 1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P = .001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P < .001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.

AB - Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT = 2.14, 1.26-3.63), IL2 (rs2069762; HRGT/TT = 1.80, 1.06-3.05), IL12B (rs3212227; HR AC/CC = 1.83, 1.06-3.06), and IL1RN (rs454078; HRAA = 1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P = .001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P < .001); the 5-year Kaplan-Meier survival estimates were 96% (93%-100%), 72% (62%-83%), and 58% (48%-72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma.

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