Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome\'s q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.

To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities.
Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking.
From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm.
In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

BACKGROUND: Since high rates of congenital anomalies (CAs), including facial CAs (FCAs), causally attributed to antenatal and community cannabis use have been reported in several recent series, it was of interest to examine this subject in detail in Europe.
METHODS: CA data were taken from the EUROCAT database. Drug exposure data were downloaded from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Income was taken from the World Bank\'s online sources.
RESULTS: On the bivariate maps of both orofacial clefts and holoprosencephaly against resin, the Δ9-tetrahydrocannabinol concentration rates of both covariates increased together in France, Bulgaria, and the Netherlands. In the bivariate analysis, the anomalies could be ranked by the minimum E-value (mEV) as congenital glaucoma > congenital cataract > choanal atresia > cleft lip ± cleft palate > holoprosencephaly > orofacial clefts > ear, face, and neck anomalies. When nations with increasing daily use were compared to those without, the former had generally higher rates of FCAs (p = 0.0281). In the inverse probability weighted panel regression, the sequence of anomalies-orofacial clefts, anotia, congenital cataract, and holoprosencephaly-had positive and significant cannabis coefficients of p = 2.65 × 10-5, 1.04 × 10-8, 5.88 × 10-16, and 3.21 × 10-13, respectively. In the geospatial regression, the same series of FCAs had positive and significant regression terms for cannabis of p = 8.86 × 10-9, 0.0011, 3.36 × 10-8, and 0.0015, respectively. Some 25/28 (89.3%) E-value estimates and 14/28 (50%) mEVs were >9 (considered to be in the high range), and 100% of both were >1.25 (understood to be in the causal range).
CONCLUSIONS: Rising cannabis use is associated with all the FCAs and fulfils the epidemiological criteria for causality. The data indicate particular concerns relating to brain development and exponential genotoxic dose-responses, urging caution with regard to community cannabinoid penetration.

BACKGROUND: Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred.
METHODS: CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank.
RESULTS: CARs were higher in countries with increasing daily use overall (p = 9.99 × 10-14, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 × 10-15, mEV = 3.04). In inverse probability weighted panel regression models the series of anomalies: all anomalies, VACTERL, foetal alcohol syndrome, situs inversus (SI), lateralization (L), and teratogenic syndromes (TS; AAVFASSILTS) had cannabis metric p-values from: p < 2.2 × 10-16, 1.52 × 10-12, 1.44 × 10-13, 1.88 × 10-7, 7.39 × 10-6 and <2.2 × 10-16. In a series of spatiotemporal models this anomaly series had cannabis metric p-values from: 8.96 × 10-6, 6.56 × 10-6, 0.0004, 0.0019, 0.0006, 5.65 × 10-5. Considering E-values, the cannabis effect size order was VACTERL > situs inversus > teratogenic syndromes > FAS > lateralization syndromes > all anomalies. 50/64 (78.1%) E-value estimates and 42/64 (65.6%) mEVs > 9. Daily cannabis use was the strongest predictor for all anomalies.
CONCLUSIONS: Data confirmed laboratory, preclinical and recent epidemiological studies from Canada, Australia, Hawaii, Colorado and USA for teratological links between cannabis exposure and AAVFASSILTS anomalies, fulfilled epidemiological criteria for causality and underscored importance of cannabis teratogenicity. VACTERL data are consistent with causation via cannabis-induced Sonic Hedgehog inhibition. TS data suggest cannabinoid contribution. SI&L data are consistent with results for cardiovascular CAs. Overall, these data show that cannabis is linked across space and time and in a manner which fulfills epidemiological criteria for causality not only with many CAs, but with several multiorgan teratologic syndromes. The major clinical implication of these results is that access to cannabinoids should be tightly restricted in the interests of safeguarding the community\'s genetic heritage to protect and preserve coming generations, as is done for all other major genotoxins.

Recent reports linking prenatal and community cannabis exposure to elevated uronephrological congenital anomaly (UCA) rates (UCAR\'s) raise the question of its European epidemiology given recent increases in community cannabinoid penetration there.
UCAR data from Eurocat. Drug use data from European Monitoring Centre for Drugs and Drug Addiction. Income from World bank.
UCAR increased across Spain, Netherlands, Poland and France. UCAR\'s and cannabis resin THC increased simultaneously in France, Spain, Netherlands and Bulgaria. At bivariate analysis all UCA\'s were related to cannabis herb and resin THC concentrations. All UCAR\'s were bivariately related to cannabis metrics ordered by median minimum E-value (mEV) as hypospadias > multicystic renal disease > bilateral renal agenesis > UCA\'s > hydronephrosis > posterior urethral valve > bladder exstrophy/epispadias. At inverse probability weighted multivariable analysis terms including cannabis were significant for the following series of anomalies: UCA\'s, multicystic renal disease, bilateral renal agenesis, hydronephrosis, congenital posterior urethral valves from P = 1.91 × 10-5, 2.61 × 10-8, 4.60 × 10-15, 4.60 × 10-15 and 2.66 × 10-10. At geospatial analysis the same series of UCA\'s were significantly related to cannabis from P = 7.84 × 10-15, 7.72 × 10-5, 0.0023, 6.95 × 10-5, and 8.82 × 10-5. 45/51 (88.2%) of E-value estimates and 31/51 (60.8%) of mEV\'s >9.
Analysis confirms a close relationship between cannabis metrics and all seven UCA\'s and fulfill formal criteria for quantitative causal inference. Given the exponential cannabinoid genotoxicity dose-response relationship results provide a powerful stimulus to constrain community cannabinoid exposure including protection of the food chain to preserve the genome and epigenome of coming generations.

Cannabinoid exposure is increasing in some European nations. Europe therefore provides an interesting test environment for the recently reported link between cannabis exposure and congenital limb anomaly (CLA) rates (CLARs). Exponential genotoxic dose-response relationships make this investigation both intriguing and imperative. Annual CLAR in 14 nations were from Epidemiological Surveillance of Congenital Anomalies. Drug use rates were from European Monitoring Centre for Drugs and Drug Dependency. Median household income was from the World Bank. E-values provide a quantitative measure of robustness of results to confounding by extraneous covariates. Inverse probability weighting is an important technique for equalizing exposures across countries and removing sources of bias. Rates of CLA, hip dysplasia and the whole group of limb anomalies were higher in countries with increasing daily cannabis use (P = 1.81 × 10-16, 0.0005 and 2.53 × 10-6, respectively). In additive inverse-probability-weighted panel models, the limb reduction-resin Δ9-tetrahydrocannabinol (THC) concentration E-value estimate was 519.93 [95% lower bound (mEV) 49.56], order Resin > Herb ≫ Tobacco > Alcohol. Elevations were noted in 86% E-value estimates and 70.2% of mEVs from 57 E-value pairs from inverse-probability-weighted panel models and from spatial models. As judged by the mEV the degree of association with metrics of cannabis exposure was hip dysplasia > polydactyly > syndactyly > limb anomalies > limb reductions with median E-value estimates from 3.40 × 1065 to 7.06 and median mEVs from 6.14 × 1033 to 3.41. Daily cannabis use interpolated was a more powerful metric of cannabis exposure than herb or resin THC exposure. Data indicate that metrics of cannabis exposure are closely linked with CLAR and satisfy epidemiological criteria for causality. Along with Hawaii and the USA, Europe now forms the third international population in which this causal link has been demonstrated. Cannabis as a predictor of limb anomalies was more potent than tobacco or alcohol. Cannabinoid access should be restricted to protect public health and the community genome/epigenome transgenerationally.

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, vascular disruptions, double outlet right ventricle, transposition of the great vessels, hypoplastic right heart, and mitral valve anomalies from 1.75 × 10-19, 4.20 × 10-11, <2.2 × 10-16, <2.2 × 10-16, 1.58 × 10-12, 4.30 × 10-9, 4.36 × 10-16, 3.50 × 10-8, 5.35 × 10-12, <2.2 × 10-16, 5.65 × 10-5 and 6.06 × 10-10. At spatial regression, terms including cannabis were positive and significant for this same list of anomalies from 0.0038, 1.05 × 10-10, 0.0215, 8.94 × 10-6, 1.23 × 10-5, 2.05 × 10-5, 1.07 × 10-6, 8.77 × 10-5, 9.11 × 10-6, 0.0001, 3.10 × 10-7 and 2.17 × 10-7. 92.6% and 75.2% of 149 E-value estimates and minimum E-values were in high zone >9; 100.0% and 98.7% >1.25. Data show many congenital cardiac anomalies exhibit strong bivariate relationships with metrics of cannabis exposure. Causal inferential modelling for the twelve anomalies selected demonstrated convincing evidence of robust relationships to cannabis which survived adjustment and fulfilled epidemiological criteria for causal relationships. Space-time regression was similarly confirmatory. Epigenomic pathways constitute viable potential mechanisms. Given exponential genotoxic dose-response effects, careful and astute control of cannabinoid penetration is indicated.

The use of Δ8THC is increasing at present across the USA in association with widespread cannabis legalization and the common notion that it is \"legal weed\". As genotoxic actions have been described for many cannabinoids, we studied the cancer epidemiology of Δ8THC. Data on 34 cancer types was from the Centers for Disease Control Atlanta Georgia, substance abuse data from the Substance Abuse and Mental Health Services Administration, ethnicity and income data from the U.S. Census Bureau, and cannabinoid concentration data from the Drug Enforcement Agency, were combined and processed in R. Eight cancers (corpus uteri, liver, gastric cardia, breast and post-menopausal breast, anorectum, pancreas, and thyroid) were related to Δ8THC exposure on bivariate testing, and 18 (additionally, stomach, Hodgkins, and Non-Hodgkins lymphomas, ovary, cervix uteri, gall bladder, oropharynx, bladder, lung, esophagus, colorectal cancer, and all cancers (excluding non-melanoma skin cancer)) demonstrated positive average marginal effects on fully adjusted inverse probability weighted interactive panel regression. Many minimum E-Values (mEVs) were infinite. p-values rose from 8.04 × 10-78. Marginal effect calculations revealed that 18 Δ8THC-related cancers are predicted to lead to a further 8.58 cases/100,000 compared to 7.93 for alcoholism and -8.48 for tobacco. Results indicate that between 8 and 20/34 cancer types were associated with Δ8THC exposure, with very high effect sizes (mEVs) and marginal effects after adjustment exceeding tobacco and alcohol, fulfilling the epidemiological criteria of causality and suggesting a cannabinoid class effect. The inclusion of pediatric leukemias and testicular cancer herein demonstrates heritable malignant teratogenesis.

Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as \'legal weed\'. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum E-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.

With reports from Australia, Canada, USA, Hawaii and Colorado documenting a link between cannabis and congenital anomalies (CAs), this relationship was investigated in Europe. Data on 90 CAs were accessed from Eurocat. Tobacco and alcohol consumption and median household income data were from the World Bank. Amphetamine, cocaine and last month and daily use of cannabis from the European Monitoring Centre for Drugs and Drug Addiction. Cannabis herb and resin Δ9-tetrahydrocannabinol concentrations were from published reports. Data were processed in R. Twelve thousand three hundred sixty CA rates were sourced across 16 nations of Europe. Nations with a higher or increasing rate of daily cannabis use had a 71.77% higher median CA rates than others [median ± interquartile range 2.13 (0.59, 6.30) v. 1.24 (0.15, 5.14)/10 000 live births (P = 4.74 × 10-17; minimum E-value (mEV) = 1.52]. Eighty-nine out of 90 CAs in bivariate association and 74/90 CAs in additive panel inverse probability weighted space-time regression were cannabis related. In inverse probability weighted interactive panel models lagged to zero, two, four and six years, 76, 31, 50 and 29 CAs had elevated mEVs (< 2.46 × 1039) for cannabis metrics. Cardiovascular, central nervous, gastrointestinal, genital, uronephrology, limb, face and chromosomalgenetic systems along with the multisystem VACTERL syndrome were particularly vulnerable targets. Data reveal that cannabis is related to many CAs and fulfil epidemiological criteria of causality. The triple convergence of rising cannabis use prevalence, intensity of daily use and Δ9-tetrahydrocannabinol concentration in herb and resin is powerfully implicated as a primary driver of European teratogenicity, confirming results from elsewhere.