Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation is believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study in healthy individuals in relation to occupational and smoking-related exposure compared to nonexposed referents. The associations (at P < 10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS, and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis, and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, the expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

• Klíčová slova
• DNA repair, cancer, chromosomal damage, double-strand break, genetics,
• MeSH
• celogenomová asociační studie MeSH
• chromozomální aberace * MeSH
• interakce genů a prostředí * MeSH
• lidé MeSH
• lymfocyty MeSH
• oprava DNA genetika   MeSH
• poškození DNA MeSH
• pracovní expozice škodlivé účinky   MeSH
• vystavení vlivu životního prostředí * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

• MeSH
• dieta MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• index tělesné hmotnosti MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   epidemiologie   MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• pití alkoholu MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Understanding the formation of risk preferences is crucial for elucidating the roots of economic, social, and health inequalities. However, this area remains inadequately explored. This study employs a risk preference measure directly linked to the labor market to examine whether previous experiences with high unemployment rates influence current risk decision-making among the elderly, and whether this impact varies by genotype. The findings indicate that individuals with low genetic predispositions for risk tolerance are more significantly influenced by historical fluctuations in unemployment rates than those with high genetic predispositions for risk tolerance. Consequently, this paper identifies genetic endowment as a crucial moderating factor that shapes how past experiences impact current decision-making processes. This disparity in how past experiences shape risk preferences based on genetic predisposition may further amplify inequalities in health, wealth, income, and other outcomes associated with risk preferences.

• Klíčová slova
• Human capital, Polygenic scores, Risk preferences, Unemployment rate,
• MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• interakce genů a prostředí * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nezaměstnanost * psychologie   MeSH
• postoj MeSH
• riskování MeSH
• rozhodování MeSH
• senioři MeSH
• socioekonomické faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Parental or ancestral environments can induce heritable phenotypic changes, but whether such environment-induced heritable changes are a common phenomenon remains unexplored. Here, we subject 14 genotypes of Arabidopsis thaliana to 10 different environmental treatments and observe phenotypic and genome-wide gene expression changes over four successive generations. We find that all treatments caused heritable phenotypic and gene expression changes, with a substantial proportion stably transmitted over all observed generations. Intriguingly, the susceptibility of a genotype to environmental inductions could be predicted based on the transposon abundance in the genome. Our study thus challenges the classic view that the environment only participates in the selection of heritable variation and suggests that the environment can play a significant role in generating of heritable variations.

• MeSH
• Arabidopsis * genetika   MeSH
• fenotyp * MeSH
• genetická variace MeSH
• genom rostlinný MeSH
• genotyp * MeSH
• interakce genů a prostředí MeSH
• regulace genové exprese u rostlin * MeSH
• transpozibilní elementy DNA * genetika   MeSH
• životní prostředí MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• transpozibilní elementy DNA * MeSH

BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

• MeSH
• celogenomová asociační studie metody   MeSH
• diabetes mellitus * genetika   MeSH
• genetická predispozice k nemoci MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   MeSH
• lidé MeSH
• mikrofilamentové proteiny genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• LRCH1 protein, human MeSH Prohlížeč
• mikrofilamentové proteiny MeSH

The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics.

• Klíčová slova
• SNPs, antioxidants, cholinergic enzymes, organophosphates, toxicogenetics,
• MeSH
• acetylcholinesterasa genetika   MeSH
• butyrylcholinesterasa genetika   MeSH
• dospělí MeSH
• glutathion-S-transferasa fí genetika   MeSH
• glutathion MeSH
• glutathiontransferasa genetika   MeSH
• GPI-vázané proteiny genetika   MeSH
• interakce genů a prostředí * MeSH
• jednonukleotidový polymorfismus * MeSH
• katalasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malondialdehyd MeSH
• mladiství MeSH
• mladý dospělý MeSH
• organofosforové sloučeniny škodlivé účinky   MeSH
• oxidační stres genetika   MeSH
• sirtuin 1 genetika   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Kamerun MeSH
• Pákistán MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• ACHE protein, human MeSH Prohlížeč
• BCHE protein, human MeSH Prohlížeč
• butyrylcholinesterasa MeSH
• glutathion-S-transferasa fí MeSH
• glutathion MeSH
• glutathione S-transferase M1 MeSH Prohlížeč
• glutathione S-transferase T1 MeSH Prohlížeč
• glutathiontransferasa MeSH
• GPI-vázané proteiny MeSH
• GSTP1 protein, human MeSH Prohlížeč
• katalasa MeSH
• malondialdehyd MeSH
• organofosforové sloučeniny MeSH
• SIRT1 protein, human MeSH Prohlížeč
• sirtuin 1 MeSH

Colorectal cancer (CRC) incidence changes with time and by variations in diet and lifestyle, as evidenced historically by migrant studies and recently by extensive epidemiologic evidence. The worldwide heterogeneity in CRC incidence is strongly suggestive of etiological involvement of environmental exposures, particularly lifestyle and diet. It is established that physical inactivity, obesity and some dietary factors (red/processed meats, alcohol) are positively associated with CRC, while healthy lifestyle habits show inverse associations. Mechanistic evidence shows that lifestyle and dietary components that contribute to energy excess are linked with increased CRC via metabolic dysfunction, inflammation, oxidative stress, bacterial dysbiosis and breakdown of gut barrier integrity while the reverse is apparent for components associated with decreased risk. This chapter will review the available evidence on lifestyle and dietary factors in CRC etiology and their underlying mechanisms in CRC development. This short review will also touch upon available information on potential gene-environment interactions, molecular sub-types of CRC and anatomical sub-sites within the colorectum.

• Klíčová slova
• Colorectal cancer, Diet, Environment, Etiology, Genetic interactions, Lifestyle, Mechanisms, Obesity,
• MeSH
• dieta * MeSH
• genetická predispozice k nemoci MeSH
• hodnocení rizik MeSH
• interakce genů a prostředí MeSH
• interakce hostitele a patogenu MeSH
• kolorektální nádory epidemiologie   etiologie   MeSH
• léky na předpis škodlivé účinky   MeSH
• lidé MeSH
• náchylnost k nemoci * MeSH
• obezita komplikace   metabolismus   MeSH
• rizikové faktory MeSH
• životní prostředí * MeSH
• životní styl * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• léky na předpis MeSH

BACKGROUND: Alcohol intake and tobacco smoking have significant negative health consequences and both are influenced by genetic predispositions. Some studies suggest that the FTO gene is associated with alcohol consumption. We investigated whether a tagging variant (rs17817449) within the FTO gene is associated with alcohol intake, problem drinking and smoking behaviour. METHODS: We analysed data from 26,792 Caucasian adults (47.2% of males; mean age 58.9 (±7.3) years), examined through the prospective cohort HAPIEE study. The primary outcomes were daily alcohol consumption, binge drinking, problem drinking (CAGE score 2+) and smoking status in relation to tagging variants within the FTO and ADH1B genes. RESULTS: We found no significant association of the FTO polymorphism with smoking status in either sex. The associations of the FTO polymorphism with drinking pattern were inconsistent and differed by gender. In men, GG homozygote carriers had lower odds of problem drinking (OR 0.85, 95% CI 0.75-0.96, p = 0.03). In women, the combination of the FTO/ADH1B GG/+A genotypes doubled the risk of binge drinking (OR 2.10, 95% CI 1.19-3.71, p < 0.05), and the risk was further increased among smoking women (OR 4.10, 95% CI 1.64-10.24, p = 0.008). CONCLUSIONS: In this large population study, the FTO gene appeared associated with binge and problem drinking, and the associations were modified by sex, smoking status and the ADH1B polymorphism.

• Klíčová slova
• ADH1B, Alcohol intake, Binge drinking, FTO, Polymorphism, Sex, Smoking,
• MeSH
• alkoholdehydrogenasa genetika   MeSH
• alkoholismus genetika   MeSH
• běloši genetika   MeSH
• gen pro FTO genetika   MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus * MeSH
• kouření genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nárazové pití alkoholu genetika   MeSH
• pití alkoholu genetika   MeSH
• prospektivní studie MeSH
• senioři MeSH
• sexuální faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADH1B protein, human MeSH Prohlížeč
• alkoholdehydrogenasa MeSH
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype-environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype-environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms.

• Klíčová slova
• disease, environment, health, pathosome, phenotype, preconditioning,
• MeSH
• čas MeSH
• epidemiologické metody MeSH
• genetická predispozice k nemoci MeSH
• genetická variace MeSH
• genotyp * MeSH
• interakce genů a prostředí * MeSH
• lidé MeSH
• modely genetické * MeSH
• nemoc genetika   MeSH
• patologie metody   MeSH
• stárnutí genetika   MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans. This was the first evidence that tick glycoproteins play a major role in allergy development with the potential to cause fatal delayed anaphylaxis to α-Gal-containing foods and drugs and immediate anaphylaxis to tick bites. Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles. The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick. Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites. The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th2 cell-mediated immunity induced by tick saliva. The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS. The presence of blood type B reduces the capacity of the immune system to produce anti-α-Gal Abs, presumably due to tolerance to α-Gal, which is very similar in structure to blood group B antigen. Therefore, individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS. Specific immunity to tick α-Gal is linked to host immunity to tick bites. Basophil activation and release of histamine have been implicated in IgE-mediated acquired protective immunity to tick infestations and chronic itch. Basophil reactivity was also found to be higher in patients with AGS when compared to asymptomatic α-Gal sensitized individuals. In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection. Anti-α-Gal IgM and IgG Abs protect humans against vector-borne pathogens and blood group B individuals seem to be more susceptible to vector-borne diseases. The link between blood groups and anti-α-Gal immunity which in turn affects resistance to vector-borne pathogens and susceptibility to AGS, suggests a trade-off between susceptibility to AGS and protection to some infectious diseases. The understanding of the environmental and molecular drivers of the immune mechanisms involved in AGS is essential to developing tools for the diagnosis, control, and prevention of this growing health problem.

• Klíčová slova
• IgE, food allergy, red meat allergy, ticks, α-Gal syndrome (AGS),
• MeSH
• alergeny imunologie   MeSH
• anafylaxe etiologie   MeSH
• červené maso MeSH
• genetická predispozice k nemoci MeSH
• hmyzí proteiny imunologie   MeSH
• imunoglobulin E metabolismus   MeSH
• interakce genů a prostředí MeSH
• klíšťata MeSH
• kousnutí klíštětem komplikace   imunologie   MeSH
• lidé MeSH
• potravinová alergie komplikace   etiologie   imunologie   MeSH
• tvorba protilátek MeSH
• zkřížené reakce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alergeny MeSH
• hmyzí proteiny MeSH
• imunoglobulin E MeSH