Polymorphisms in complement system genes and risk of non-Hodgkin lymphoma

Environ Mol Mutagen. 2012 Mar;53(2):145-51. doi: 10.1002/em.21675. Epub 2011 Dec 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Complement System Proteins / genetics*
  • Complement System Proteins / immunology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / immunology
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk
  • Serine Endopeptidases / genetics
  • Young Adult

Substances

  • Complement System Proteins
  • Serine Endopeptidases
  • C1RL protein, human