ABSTRACT
At the end of the last century, human trichinellosis was an important public health problem in the eastern parts of Croatia. Moreover, the majority of clinically infected people were registered in Vukovar-Srijem County (up to 60% of all human cases registered in Croatia). Also, 95% of all Trichinella positive swine carcasses originated from Vukovar-Srijem County. Beside the health threat, trichinellosis implied not only notable economic expenses but also threatened to endanger traditional way of life and eating habits. In order to reduce all negative consequences of the disease, a multidisciplinary Working group for trichinellosis was founded. The group consisted of scientists and experts from different fields of work, who helped and significantly contributed to minimizing the threats of trichinellosis as well as to maintaining and preserving the method of traditional processing and consumption of swine meat. The members, the methods and the results of the Working group activities will be discussed in this paper.
Subject(s)
Food Parasitology , Trichinellosis/epidemiology , Trichinellosis/prevention & control , Animals , Biomedical Research , Croatia , Disease Outbreaks , Food Contamination , Humans , Interdisciplinary Communication , Meat , Program Development , Public Health , Swine , Trichinella , Trichinellosis/parasitologyABSTRACT
Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Subject(s)
Chernobyl Nuclear Accident , Iodine Radioisotopes , Lymphatic Metastasis , Mutation , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Lymphatic Metastasis/genetics , Male , Adult , Female , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Adolescent , Proto-Oncogene Proteins B-raf/genetics , Young Adult , Lymph Nodes/pathology , Proto-Oncogene Proteins c-ret/genetics , Child , Genomics , Middle Aged , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Gene Expression Profiling , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms, Radiation-Induced/genetics , Neoplasms, Radiation-Induced/pathology , Neck/pathology , Gene Expression Regulation, NeoplasticABSTRACT
The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood 131I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.
Subject(s)
Chernobyl Nuclear Accident , Mutation , Neoplasms, Radiation-Induced/genetics , Thyroid Cancer, Papillary/etiology , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/etiology , Thyroid Neoplasms/genetics , Adolescent , Adult , Child , Child, Preschool , DNA Copy Number Variations , Epigenome , Female , Gene Expression Profiling , Genes, ras , Genetic Variation , Humans , Infant , Iodine Radioisotopes , Loss of Heterozygosity , Male , Middle Aged , Proto-Oncogene Proteins B-raf/genetics , RNA-Seq , Radiation Dosage , Thyroid Gland/physiology , Thyroid Gland/radiation effects , Translocation, Genetic , Ukraine , Whole Genome Sequencing , Young AdultABSTRACT
The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era.