The aim of this study is to analyze the genotoxic risks in the Moravian-Silesian Region in the Czech Republic and assess the significance of genotoxic factors in the etiology of cancer by bringing together the Registry of Occupational Exposure to Genotoxic Factors and the Cancer Registry and compare the rate of detected cancer in persons exposed to genotoxic factors via their work in the Moravian-Silesian Region with the occurrence of cancer in the population of the Czech Republic. The results show: (a) For the monitored group (748 person) for the period 1996-2008, according to gender, was no statistically significant difference in the incidence of oncological diseases compared to the population of the Czech Republic. (b) But statistically significant difference was found in the cases of oncological diseases in groups according to % AB.C. using the Cytogenetic analysis of human peripheral lymphocytes (CAPL). The highest incidence was in the group with a higher incidence of % AB.C. High values of % AB.C. may predict the development of oncological diseases.
- MeSH
- Incidence MeSH
- Humans MeSH
- Mutagens toxicity MeSH
- Neoplasms chemically induced epidemiology MeSH
- Occupational Exposure * MeSH
- Registries MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations. METHODS: The SIM1 promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2-18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the SIM1 variant carriers were compared with clinical phenotypes of 4 MC4R variant carriers and with 27 unrelated SIM1 and MC4R mutation negative obese controls that were matched for age and gender. RESULTS: Seven previously described SIM1 variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 in silico software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m2; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (p = 0.02) and low fat, low carbohydrate, high protein (p = 0.02) foods compared to the obese controls. CONCLUSIONS: We have identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.
- MeSH
- Genetic Carrier Screening MeSH
- Child MeSH
- Phenotype MeSH
- Humans MeSH
- Adolescent MeSH
- Mutation MeSH
- Calorimetry, Indirect MeSH
- Obesity ethnology genetics MeSH
- Child, Preschool MeSH
- Food Preferences MeSH
- Receptor, Melanocortin, Type 4 genetics MeSH
- Repressor Proteins genetics MeSH
- Pedigree MeSH
- Case-Control Studies MeSH
- Severity of Illness Index MeSH
- Basic Helix-Loop-Helix Transcription Factors genetics MeSH
- Age of Onset MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic ethnology MeSH
- Slovakia ethnology MeSH
Cílem práce byla analýza genotoxického rizika v MSK a posouzení významu genotoxických faktorů v etiologii nádorových onemocnění prostřednictvím propojení registru profesionálních expozic genotoxickým faktorům s nádorovým registrem a srovnání frekvence zjištěných nádorových onemocnění u osob profesionálně exponovaných genotoxickým faktorům v MSK s výskytem nádorových onemocnění u populace v České republice. Soubor tvořilo 748 osob, u nichž byly k dispozici záznamy o profesionální expozici od roku 2005, které byly alespoň 1x aktualizovány. Nejčastějšími karcinogeny byly polycyklické aromatické uhlovodíky (PAU), konkrétně benzo[a]pyren, benzo[d,e,f]chryzen a cytostatika aplikovaná ve zdravotnických zařízeních. Soubor byl propojen s nádorovým registrem v Ostravě v červnu 2009 a podruhé v červnu 2011. Bylo zjištěno 22 nádorových onemocnění v roce 2009 a 27 nádorových onemocnění v roce 2011. Nebyl zjištěn staticky významný rozdíl ve výskytu nádorových onemocnění (C 00–C 97, D 00–D 09) v daném souboru v letech 1996–2009 a výskytu nádorových onemocnění v populaci České republiky v daných věkových skupinách. V rámci provedených cytogenetických analýz lidských periferních lymfocytů byl zjištěn statisticky významný rozdíl (p = 0,043) v zastoupení případů nádorových onemocnění ve skupinách dle % AB.B. Největší výskyt byl ve skupině s větším výskytem (≥4 %) AB.B. Důvody pro relativně nízký výskyt nádorových onemocnění u osob exponovaných genotoxickým látkám mohou být ve snížení expozic genotoxickým látkám v důsledku opatření nařízených hygienickou službou po prokázání zvýšené hodnoty chromozomových aberací v rizikových provozech.
The object of this study is to present an analysis of genotoxic risks in the Moravian–Silesian Region and assess the significance of genotoxic factors in the etiology of cancer by bringing together the Registry of Occupational Exposure to Genotoxic Factors and Cancer Registry and compare the rate of detected cancer in persons professionally exposed to genotoxic factors in the Moravian–Silesian Region with the occurrence of cancer in the population of the Czech Republic. The set of individuals consisted of 748 subjects whose records of occupational exposure have been available since 2005 and have been updated at least once. The most common carcinogens were polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene, benzo[d,e,f]chrysene and cytostatics applied in healthcare facilities. The file was linked to the Cancer Registry in Ostrava in June 2009 and again in June 2011 with 22 cases of cancer recorded in 2009 and 27 cases of cancer in 2011. There was no statistically significant difference between the incidence of cancer (C 00–C 97, D 00–D 09) in the 1996–2009 cohort and the incidence of cancer in the population of the Czech Republic in the relevant age groups. A statistically significant difference (p = 0.043) was detected in cases of cancer in groups according to % AB.B. The greatest incidence was detected in the group with a higher incidence of (≥4%) AB.B. The reasons for the relatively low incidence of cancer in people exposed to genotoxic agents may be due to reduced exposure to genotoxic agents as a result of measures ordered by the Public Health Authority following demonstrably increased levels of chromosomal aberrations in high-risk environments.
- MeSH
- Cytogenetic Analysis methods MeSH
- Carcinogens, Environmental * metabolism adverse effects MeSH
- Air Pollutants, Occupational * isolation & purification adverse effects MeSH
- Humans MeSH
- Neoplasms * epidemiology etiology genetics chemically induced classification MeSH
- Occupational Exposure * standards prevention & control adverse effects MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Review MeSH
- Keywords
- denzita kostního minerálu,
- MeSH
- Densitometry statistics & numerical data utilization MeSH
- Adult MeSH
- Financing, Organized MeSH
- Body Mass Index MeSH
- Clinical Trials as Topic MeSH
- Bone Density MeSH
- Middle Aged MeSH
- Humans MeSH
- Obesity surgery metabolism MeSH
- Osteoporosis metabolism pathology prevention & control MeSH
- Aged MeSH
- Adipose Tissue MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
