title: Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma.
abstract: The complement system plays an important role in inflammatory and immune responses, and recent evidence has suggested that it may also play a role in lymphomagenesis. We evaluated the association between genetic variation in complement system genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study conducted among women in Connecticut. Tag SNPs in 30 complement genes were genotyped in 432 Caucasian incident cases and 494 frequency-matched controls. A gene-based analysis that adjusted for the number of tag SNPs genotyped in each gene showed a significant association with NHL overall (P = 0.04) as well as with diffuse large B-cell lymphoma (DLBCL) (P = 0.01) for the C1RL gene. A SNP-based analysis showed that a C>T base substitution for C1RL rs3813729 (odds ratio (OR)(CT) = 0.60, 95% confidence interval (CI) = 0.42-0.87, P(trend) = 0.0062) was associated with a decreased risk of overall NHL, as well as for DLBCL (OR(CT) = 0.39, 95% CI = 0.20-0.73; P(trend) = 0.0034). Additionally, SNPs (C2 rs497309, A>C and C3 rs344550, G>C) in two complement genes were positively associated with marginal zone lymphoma (MZL) and C1QG was associated with CLL/SLL, but these results were based on a limited number of cases. Our results suggest a potential role of the complement system in susceptibility to NHL; however, our results should be viewed as exploratory and further replication is needed to clarify these preliminary findings.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892-7240, USA. bryan.bassig@yale.edu
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Bassig
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holford
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Brian
authors.initials: B
authors.lastname: Leaderer
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Zou
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012697:Serine Endopeptidases / Q000235:genetics; D055815:Young Adult
chemical_list: D003165:Complement System Proteins; D012697:Serine Endopeptidases; C502014:C1RL protein, human