ABSTRACT
Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Chromosomes, Human, Pair 19/genetics , Genetic Predisposition to Disease , Hodgkin Disease/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Genetic Variation , Genome-Wide Association Study , Humans , Male , Middle Aged , Young AdultABSTRACT
Cytogenetic studies in rescue rangers of the Russian Ministry of Emergencies has shown that this category of specialists are exposed to genotoxic factors during their professional activity. The level of induction of cytogenetic injuries of rescue team members depended on labor conditions, genotype (glutathione-S-transferase M1 and T1 xenobiotic detoxication genes), and tobacco smoking.
Subject(s)
Cytogenetics/methods , Occupational Health Services/methods , Rescue Work , Adult , Chromosome Aberrations , Emergencies , Genotype , Glutathione Transferase/genetics , Humans , Polymorphism, Genetic , Russia , SmokingABSTRACT
This investigation was performed to test a supposition about the influence of disturbances in antioxidative system on cytogenetical parameters in Chernobyl' clean-up workers. It was shown that some cytogenetical parameters straightly correlated with the parameters of oxidative stress, while other cytogenetical parameters show just reverse correlations. Apparently, these relationships are not of cause-and-effect type, but they reflect a complex processes occurring in humans for a long period after radiation exposure.
