[Molecular genetic analysis of the interleukin 6 and tumor necrosis factor alpha gene polymorphisms in multiple myeloma].
ABSTRACT The-174G alpha-->C polymorphism of the interleukin 6 (IL-6) gene promoter and the-308G alpha-->A polymorphism of the tumor necrosis factor alpha (TNF alpha) gene promoter were tested for association with multiple myeloma (MM) varying in severity. Of 69 patients, 19 had aggressive MM, 26 had benign MM, and 24 had unidentified MM. The control group (N = 102) matched the test group in age and sex composition. The two groups did not significantly differ in allele and genotype frequencies of the IL-6 and TNF alpha genes. Genotype CC, which determines low-level expression of IL-6, occurred at a frequency of 0.35 in patients with low-progressing MM and was absent from patients with aggressive MM. The TNF alpha gene showed no association with predisposition to MM or clinical variant of the disease. On this evidence, the polymorphic variants of the cytokine genes were assumed to have no effect on predisposition to MM. As for MM progression, genotype CC of the IL-6 gene was associated with milder clinical signs in patients from Bashkortostan.
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ABSTRACT: To describe the risk patterns of multiple myeloma in Los Angeles County (LAC). Incident multiple myeloma cases diagnosed from 1972 to 1999 were ascertained by the population-based cancer registry for LAC. Average annual age-specific and age-adjusted incidence rates (AAIR), standardized to the 2000 US census age distribution, were calculated using age-, race-, sex- and socioeconomic status (SES)-specific denominators estimated for all years from US census data for 1970, 1980 and 1990. Odds ratios (ORs) for risk by birthplace and religion were estimated using multivariate logistic regression, comparing multiple myeloma patients with other cancer patients. All groups experienced increasing incidence with age; African-Americans experienced the steepest increase which began a decade earlier compared to other groups. Overall incidence rates were 50% higher among males (n = 4,692) than females (n = 4,343) (p < 0.05). AAIRs were highest for African-Americans, followed by Spanish-surnamed whites (SSW), non-Spanish-surnamed whites (NSSW), Filipinos and other Asian groups. Among African-Americans, incidence rates increased with increasing SES. US-born SSW had 14% lower risk compared to non-US born SSW (OR = 0.86, 95% confidence interval [CI] = 0.74-0.99]. Jews had an 11% higher risk compared to Protestants (OR = 1.11; 95% CI = 0.99-1.24). Risk patterns suggest a role for both environmental and genetic factors.Cancer Causes and Control 09/2006; 17(7):931-8. · 3.20 Impact Factor
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ABSTRACT: Allelic distribution of -308 G>A (TNF 1/2) polymorphism of the TNF-alpha, and the +252 A>G promoter polymorphism of the LT-alpha gene, the 1267 A>G polymorphism of the HSP70-2 gene as well as the -429 T>C promoter polymorphism of the RAGE gene were tested in 94 MM cases and 141 controls. Significantly less MM patients than controls carried the TNF2 allele (p=0.018) and the TNF2-LTA 252G haplotype (p=0.025). The difference was, however, restricted to the females, as well as the relatively young (<69 years) subjects. By contrast, we did not find differences with the other SNPs tested.Leukemia Research 11/2008; 32(10):1499-504. · 2.76 Impact Factor
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ABSTRACT: Abstract Context: Interleukin-6 (IL-6) is implicated in the pathophysiology of hematologic neoplasia. Objective: To review the role of IL-6 single nucleotide polymorphisms (SNPs) in hematologic neoplasia. Methods: PubMed and EMBASE search of genetic association studies. Effects were summarized using the model-free generalized odds ratio (ORG), and the mode of inheritance was estimated for significant associations. Results: Seventeen articles provided data on 20 distinct SNPs. The IL-6 receptor rs8192284 was associated with an increased risk of hematologic malignancy (combined ORG 1.42, 95%CI 1.03-1.96), including multiple myeloma (ORG 1.39, 95%CI 0.99-1.95). The IL-6 promoter rs1800795 conferred protection against young adult Hodgkin's disease (ORG 0.68, 95%CI 0.48-0.95). Significant single-study effects for four other SNPs-disease associations were estimated. The IL-6 promoter rs1800795 and rs1800797 were not associated with overall susceptibility to non-Hodgkin's lymphomas. Conclusions: There is accumulating evidence that the IL-6 promoter, receptor and signal transducer SNPs can modify disease susceptibility.Biomarkers 09/2013; · 1.88 Impact Factor