ABSTRACT
In an International Lymphoma Epidemiology Consortium pooled analysis, polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk. Here, 8,847 participants were added to previous data (patients diagnosed from 1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds ratios were estimated for non-Hispanic whites and several ethnic subgroups using 2-sided tests. Consistent with previous findings, odds ratios were increased for "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) = 1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) = 1.23, P(trend) = 0.004). In the combined population, odds ratios were increased for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL: OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic) = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12, P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL etiology.
Subject(s)
Lymphoma, Non-Hodgkin/genetics , Lymphotoxin-alpha/genetics , Polymorphism, Single Nucleotide , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Australia/ethnology , Canada/ethnology , Case-Control Studies , Europe/ethnology , Female , Genetic Predisposition to Disease , Humans , Interleukin-10/genetics , International Agencies , Lymphoma, Non-Hodgkin/ethnology , Male , Middle Aged , Risk Factors , United States/ethnology , White People/genetics , Young AdultSubject(s)
Cysts/pathology , HIV Infections/pathology , HIV-1 , Lymphocytosis/pathology , Magnetic Resonance Imaging , Parotid Diseases/pathology , Adult , CD8-Positive T-Lymphocytes/pathology , Cysts/virology , HIV Infections/complications , Humans , Lymphocytosis/virology , Male , Parotid Diseases/virologyABSTRACT
Soy and red-clover isoflavones are commonly consumed within the diet or as a dietary supplement due to a range of presumed beneficial health benefits. These isoflavones are thought to protect against heart diseases as well as breast and other types of cancer. Isoflavones are structurally similar to estrogens and may act as estrogen agonists or antagonists by binding to estrogen receptors. Because of an increased use of isoflavones in processed foods and dietary supplements as well as the greater consumption of soy products, dietary intakes of isoflavones are increasing in children and adolescents in North America. Estrogens are a known component of numerous hormone related cancers including breast cancer. It is with these facts in mind that we review the existing epidemiological and experimental animal studies for a resolution to a proposed correlation between increased isoflavone consumption and breast cancer. There is conflicting evidence from epidemiological, intervention and experimental animal studies regarding the chemopreventing effects of soy isoflavones in breast cancer. Isoflavones are weak estrogens and their effect depends upon the dose, time of exposure and species involved. It would, therefore, not be safe to indisputably accept soy or red-clover as a source of isoflavone resource to prevent breast cancer.
