Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma
BLOOD
Authors: Colt, Joanne S.; Rothman, Nathaniel; Severson, Richard K.; Hartge, Patricia; Cerhan, James R.; Chatterjee, Nilanjan; Cozen, Wendy; Morton, Lindsay M.; De Roos, Anneclaire J.; Davis, Scott; Chanock, Stephen; Wang, Sophia S.
Abstract
Organochlorine exposure was linked to non-Hodgkin lymphoma (NHL) risk. To determine whether this relation is modified by immune gene variation, we genotyped 61 polymorphisms in 36 immune genes in 1172 NHL cases and 982 controls from the National Cancer Institute Surveillance, Epidemiology, and End Results (NCI-SEER) study. We examined 3 exposures with elevated risk in this study: PCB180 (plasma, dust measurements), the toxic equivalency quotient (an integrated functional measure of several organochlorines) in plasma, and alpha-chlordane (dust measurements, selfreported termiticide use). Plasma (100 cases, 100 controls) and dust (682 cases, 513 controls) levels were treated as natural log-transformed continuous variables. Unconditional logistic regression was used to calculate beta coefficients and odds ratios, stratified by genotype. Associations between all 3 exposures and NHL risk were limited to the same genotypes for IFNG (C-1615T) TT and IL4 (5'-UTR, Ex1-168C>T) CC. Associations between PCB180 in plasma and dust and NHL risk were limited to the same genotypes for IL16 (3'-UTR, Ex22+871A>G) AA, IL8 (T-251A) TT, and IL10 (A-1082G) AG/GG. This shows that the relation between organochlorine exposure and NHL risk may be modified by particular variants in immune genes and provides one of the first examples of a potential gene-environment interaction for NHL. (Blood. 2009; 113: 1899-1905)
Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease
REVISTA CLINICA ESPANOLA
Authors: Novo-Veleiro, I.; Cieza-Borrella, C.; Pastor, I.; Gonzalez-Sarmiento, R.; Laso, F. -J.; Marcos, M.
Abstract
Introduction: Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-kappa B pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-kappa B pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL128 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL 1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. Patients and methods: The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan (R) PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Results: Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of allele T carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Conclusions: Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development. (C)2018 Elsevier Espana, S.L.U. and Sociedad Espanola de Medicina Interna (SEMI). All rights reserved.