Common variants in genes that mediate immunity and risk of multiple myeloma

Int J Cancer. 2007 Jun 15;120(12):2715-22. doi: 10.1002/ijc.22618.

Abstract

Multiple myeloma (MM) is a B-cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21-84 years and 545 population-based controls, we examined the risk of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation-maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (-28120T, rs2107356) and FCGR2A (-120G, rs1801274) (OR = 1.91, 95% CI 1.08-3.38 and 1.95, 95% CI 1.06-3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering part of the LTA*TNF complex (LTA -82C/-90G *TNF -1036C/-487G/-417G, OR = 1.63, 95% CI 1.02-2.16) compared with the most frequently occurring haplotype observed among controls (LTA -82A/-90A *TNF -1036C/-487G/-417G). Our findings provide preliminary evidence that common genetic variants in specific immune-mediated pathways could influence the risk of MM.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Immunity*
  • Linkage Disequilibrium
  • Middle Aged
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Mutation*
  • Odds Ratio
  • Risk Factors