title: Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma.
abstract: Interleukin-6 (IL-6) promotes normal plasma cell development and proliferation of myeloma cells in culture. We evaluated IL-6 genotypes and body mass index (BMI) in a case-control study of multiple myeloma and plasmacytoma. DNA samples and questionnaires were obtained from incident cases of multiple myeloma (n = 134) and plasmacytoma (n = 16; plasma cell neoplasms) ascertained from the Los Angeles County population-based cancer registry and from siblings or cousins of cases (family controls, n = 112) and population controls (n = 126). Genotypes evaluated included IL-6 promoter gene single nucleotide polymorphisms (SNP) at positions -174, -572, and -597; one variable number of tandem repeats (-373 A(n)T(n)); and one SNP in the IL-6 receptor (IL-6ralpha) gene at position -358. The variant allele of the IL-6 promoter SNP -572 was associated with a roughly 2-fold increased risk of plasma cell neoplasms when cases were compared with family [odds ratio (OR), 1.8; 95% confidence interval (95% CI), 0.7-4.7] or population controls (OR, 2.4; 95% CI, 1.2-4.7). The -373 9A/9A genotype was associated with a decreased risk compared with the most common genotype (OR for cases versus family controls, 0.4; 95% CI, 0.1-1.7; OR for cases versus population controls, 0.3; 95% CI, 0.1-0.9). No other SNPs were associated with risk. Obesity (BMI >or= 30 kg/m(2)) increased risk nonsignificantly by 40% and 80% when cases were compared with family controls or population controls, respectively, relative to persons with a BMI of <25 kg/m(2). These results suggest that IL-6 promoter genotypes may be associated with increased risk of plasma cell neoplasms.
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MC 9175, Los Angeles, CA 90089-9175, USA. wcozen@usc.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Mulugeta
authors.initials: M
authors.lastname: Gebregziabher
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Coetzee
authors.forename: Sophia S
authors.initials: SS
authors.lastname: Wang
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Ann
authors.initials: A
authors.lastname: Morhbacher
authors.forename: Simon G
authors.initials: SG
authors.lastname: Coetzee
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Salam
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Zadnick
authors.forename: Sue A
authors.initials: SA
authors.lastname: Ingles
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology*; D010954:Plasmacytoma / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D015850:Interleukin-6