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Germline variation in complement genes and event‐free survival in follicular and diffuse large B‐cell lymphoma
Author(s) -
Charbonneau Bridget,
Maurer Matthew J.,
Fredericksen Zachary S.,
Zent Clive S.,
Link Brian K.,
Novak Anne J.,
Ansell Stephen M.,
Weiner George J.,
Wang Alice H.,
Witzig Thomas E.,
Dogan Ahmet,
Slager Susan L.,
Habermann Thomas M.,
Cerhan James R.
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23273
Subject(s) - single nucleotide polymorphism , follicular lymphoma , diffuse large b cell lymphoma , immunology , rituximab , oncology , medicine , proportional hazards model , cd46 , biology , complement component 3 , complement system , lymphoma , gene , immune system , complement receptor , genetics , genotype
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. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.