title: Common variants in genes that mediate immunity and risk of multiple myeloma.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. elbrown@uab.edu
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Shelia
authors.initials: S
authors.lastname: Hoar-Zahm
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007109:Immunity; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D009154:Mutation; D016017:Odds Ratio; D012307:Risk Factors