Interleukin-6-related genotypes, body mass index, and risk of multiple myeloma and plasmacytoma.
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.
Cozen
Wendy
W
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
Gebregziabher
Mulugeta
M
Conti
David V
DV
Van Den Berg
David J
DJ
Coetzee
Gerhard A
GA
Wang
Sophia S
SS
Rothman
Nathaniel
N
Bernstein
Leslie
L
Hartge
Patricia
P
Morhbacher
Ann
A
Coetzee
Simon G
SG
Salam
Muhammad T
MT
Wang
Wei
W
Zadnick
John
J
Ingles
Sue A
SA
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
D015850:Interleukin-6