Risk of non-Hodgkin lymphoma in association with germline variation in complement genes

Br J Haematol. 2009 Jun;145(5):614-23. doi: 10.1111/j.1365-2141.2009.07675.x. Epub 2009 Mar 30.

Abstract

Germline mutations in complement genes have been associated with susceptibility to infections and autoimmune diseases, conditions that are associated with non-Hodgkin lymphoma (NHL) risk. To test the hypothesis that common genetic variation in complement genes affect risk of NHL, we genotyped 167 single nucleotide polymorphisms (SNPs) from 31 genes in 441 NHL cases and 475 controls. Principal components (PC) and haplotype analyses were used for gene-level tests of NHL risk, while individual SNPs were modelled as having a log-additive effect. In gene level PC analyses, C2 (P = 0.023), C5 (P = 0.0032) and C9 (P = 0.020) were associated with NHL risk; haplotype analyses showed similar results, as well as a haplotype association for C7 (P = 0.046). When all four genes were considered simultaneously, only C5 and C9 remained significant (P < 0.05). In SNP level results from these genes, 10 SNPs had a P < 0.05. However, after correcting for multiple testing, only the C5 SNPs rs7026551 (q = 0.015; OR = 1.54, 95% CI 1.21-1.95) and rs2416810 (q = 0.015; OR = 1.57; 95% CI 1.22-2.01), and the C9 SNP rs187875 (q = 0.015; OR = 0.68; 95% 0.56-0.84) remained noteworthy. Associations were similar for the common NHL subtypes. In summary, we provide evidence for a role of genetic variation in complement genes, particularly C5 and C9, and NHL risk.

MeSH terms

  • Case-Control Studies
  • Chromosome Mapping
  • Complement C5 / genetics
  • Complement C9 / genetics
  • Complement System Proteins / genetics*
  • Complement System Proteins / immunology
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Haplotypes
  • Humans
  • Logistic Models
  • Lymphoma, Non-Hodgkin / genetics*
  • Lymphoma, Non-Hodgkin / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Principal Component Analysis
  • Risk Assessment / methods
  • TNF Receptor-Associated Factor 1 / genetics

Substances

  • Complement C5
  • Complement C9
  • TNF Receptor-Associated Factor 1
  • Complement System Proteins