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 À174, À572, and À597; one variable number of tandem repeats (À373 A n T n ); and one SNP in the IL-6 receptor (IL-6ra) gene at position À358. The variant allele of the IL-6 promoter SNP À572 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 À373 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 z 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. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2285 -91)

Body Mass Index, Physical Activity, and Risk of Multiple Myeloma

“…In conclusion, the present findings are consistent with previous reports of increasing risk of multiple myeloma with increasing BMI (6)(7)(8)(9)(10)(11). This observation has been made across both cohort (6,8,9) and case-control (7, 10, 11) studies, and in Caucasian (6-8, 10), African-American (7), and Asian (9) populations, using a single baseline or frequently updated assessment of BMI.…”

“…The present findings are therefore consistent with the published literature. Of interest, the previous studies relied on a single (enrollment) classification of BMI (6)(7)(8)(9)(10)(11). The similarity of the present report with those studies argues against an important effect of misclassification of BMI on the prior findings.…”

“…Of note, several large population-based studies have reported an increased risk of multiple myeloma with increasing body mass index (BMI; refs. [6][7][8][9][10][11]. Those studies suggested that persons classified as ''obese'' by the common WHO definitions (i.e., BMI, z30 kg/m 2 ; ref.…”

“…However, it remains uncertain whether physical activity is also associated with this malignancy. In addition, the prior findings may be influenced by misclassification of BMI due to their reliance on a single (enrollment) assessment of adult weight (6)(7)(8)(9)(10)(11). Thus, to further examine the relation of energy balance with multiple myeloma, we conducted prospective analyses of BMI and physical activity in the Nurses' Health Study and Health Professionals Followup Study cohorts.…”

Diabetes and the risk of non-Hodgkin's lymphoma and multiple myeloma in the European Prospective Investigation into Cancer and Nutrition

“…Interleukin-6 promotes normal plasma cell development and proliferation of myeloma cells in culture, and has been associated with an increased risk of plasma cell neoplasms. 45 Cozen et al found that the variant allele of the interleukin promoter single nucleotide polymorphism -572 was associated with a 2-fold increased risk of plasma cell neoplasms, compared to the risk in family and population controls. 45 Increased concentrations of interleukin-6 and interleukin-12 were also found in blood plasma, culture supernatant and isolated and broken lymphocytes from patients with B-CLL.…”