Journal article
Germline Variation in Complement Genes and Event-Free Survival in Follicular and Diffuse Large B-Cell Lymphoma
American journal of hematology, Vol.87(9), pp.880-885
09/2012
DOI: 10.1002/ajh.23273
PMCID: PMC3586263
PMID: 22718493
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.
Details
- Title: Subtitle
- Germline Variation in Complement Genes and Event-Free Survival in Follicular and Diffuse Large B-Cell Lymphoma
- Creators
- Bridget Charbonneau - Department of Health Sciences Research, Mayo Clinic, Rochester, MinnesotaMatthew J Maurer - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MinnesotaZachary S Fredericksen - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MinnesotaClive S Zent - Division of Hematology, Mayo Clinic, Rochester, MinnesotaBrian K Link - College of Medicine, University of Iowa, Iowa City, IowaAnne J Novak - Division of Hematology, Mayo Clinic, Rochester, MinnesotaStephen M Ansell - Division of Hematology, Mayo Clinic, Rochester, MinnesotaGeorge J Weiner - College of Medicine, University of Iowa, Iowa City, IowaAlice H Wang - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MinnesotaThomas E Witzig - Division of Hematology, Mayo Clinic, Rochester, MinnesotaAhmet Dogan - Division of Hematopathology, Mayo Clinic, Rochester, MinnesotaSusan L Slager - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MinnesotaThomas M Habermann - Division of Hematology, Mayo Clinic, Rochester, MinnesotaJames R Cerhan - Division of Epidemiology, Mayo Clinic, Rochester, Minnesota
- Resource Type
- Journal article
- Publication Details
- American journal of hematology, Vol.87(9), pp.880-885
- DOI
- 10.1002/ajh.23273
- PMID
- 22718493
- PMCID
- PMC3586263
- ISSN
- 0361-8609
- eISSN
- 1096-8652
- Grant note
- R01 CA129539 || CA / National Cancer Institute : NCI R25 CA092049 || CA / National Cancer Institute : NCI P50 CA097274 || CA / National Cancer Institute : NCI
- Language
- English
- Date published
- 09/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094399802771
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