Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma

Bridget Charbonneau, Matthew J. Maurer, Zachary S. Fredericksen, Clive S. Zent, Brian K. Link, Anne J Novak, Stephen Maxted Ansell, George J. Weiner, Alice H. Wang, Thomas Elmer Witzig, Ahmet Dogan, Susan L Slager, Thomas Matthew Habermann, James R Cerhan

Research output: Contribution to journalArticle

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Abstract

The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular lymphoma (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N = 107) and DLBCL (N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (P = 0.009), CD55 (P = 0.006), CFHR5 (P = 0.01), C9 (P = 0.02), CFHR1 (P = 0.03), and CD46 (P = 0.03) were significant at P < 0.05, and these genes remained noteworthy after accounting for multiple testing (q < 0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (P = 0.001) and C7 (P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the regulators of complement activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis.

Original languageEnglish (US)
Pages (from-to)880-885
Number of pages6
JournalAmerican Journal of Hematology
Volume87
Issue number9
DOIs
StatePublished - Sep 2012

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Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Disease-Free Survival
Genes
Innate Immunity
Single Nucleotide Polymorphism
Gene Components
Complement Activation
Regulator Genes
B-Lymphocytes
Cohort Studies
Prospective Studies

ASJC Scopus subject areas

  • Hematology

Cite this

Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma. / Charbonneau, Bridget; Maurer, Matthew J.; Fredericksen, Zachary S.; Zent, Clive S.; Link, Brian K.; Novak, Anne J; Ansell, Stephen Maxted; Weiner, George J.; Wang, Alice H.; Witzig, Thomas Elmer; Dogan, Ahmet; Slager, Susan L; Habermann, Thomas Matthew; Cerhan, James R.

In: American Journal of Hematology, Vol. 87, No. 9, 09.2012, p. 880-885.

Research output: Contribution to journalArticle

Charbonneau, Bridget ; Maurer, Matthew J. ; Fredericksen, Zachary S. ; Zent, Clive S. ; Link, Brian K. ; Novak, Anne J ; Ansell, Stephen Maxted ; Weiner, George J. ; Wang, Alice H. ; Witzig, Thomas Elmer ; Dogan, Ahmet ; Slager, Susan L ; Habermann, Thomas Matthew ; Cerhan, James R. / Germline variation in complement genes and event-free survival in follicular and diffuse large B-cell lymphoma. In: American Journal of Hematology. 2012 ; Vol. 87, No. 9. pp. 880-885.
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AU - Charbonneau, Bridget

AU - Maurer, Matthew J.

AU - Fredericksen, Zachary S.

AU - Zent, Clive S.

AU - Link, Brian K.

AU - Novak, Anne J

AU - Ansell, Stephen Maxted

AU - Weiner, George J.

AU - Wang, Alice H.

AU - Witzig, Thomas Elmer

AU - Dogan, Ahmet

AU - Slager, Susan L

AU - Habermann, Thomas Matthew

AU - Cerhan, James R

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N2 - The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event-free survival (EFS) in follicular lymphoma (FL) and diffuse large B-cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N = 107) and DLBCL (N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene-level analyses, we used a principal components based gene-level test. In gene-level analyses for FL EFS, CFH (P = 0.009), CD55 (P = 0.006), CFHR5 (P = 0.01), C9 (P = 0.02), CFHR1 (P = 0.03), and CD46 (P = 0.03) were significant at P < 0.05, and these genes remained noteworthy after accounting for multiple testing (q < 0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (P = 0.001) and C7 (P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the regulators of complement activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32-q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis.

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