Comprehensive analysis based in silico study of alternative bisphenols - Environmental explanation of prostate cancer progression.

Industries have begun to shift their focus on exploring substitute chemicals for BPA due to their concerns about safety and environmental pollution. In recent years, alternative bisphenols, including BPS, BPF, and BPAF have been extensively used as BPA substitutes. Based on previous studies, BPA is considered a risk factor for prostate cancer. This work aims to explore the interactive genes related to alternative bisphenols and prostate cancer using the TCGA, CTD, and GEO databases. After performing the GO and KEGG enrichment analysis, a correlation between alternative bisphenols and prostate cancer was detected using bioinformatics analysis. Among the interactive genes of alternative bisphenols, ferroptosis-related genes revealed strong correlations with prostate cancer. Moreover, the prognostic predictive model, ROC curve, and survival analysis confirmed that ferroptosis-related genes displayed a strong correlation in the prognosis of prostate cancer. We successfully evaluated the relationship between prostate cancer and alternative bisphenols; as a result, a novel approach was proposed to explore the damaging effect of environmental endocrine disruptors.

No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy.

BACKGROUND: In March 2014, the European Commission issued a new regulation restricting the content of hexavalent chromium (Cr) in leather to no more than 3 mg/kg. We previously performed a questionnaire study in January 2014 to characterize our patients with Cr contact allergy prior to regulatory intervention. OBJECTIVES: To assess whether clinical characteristics, self-reported sources of Cr exposure, and burden of disease changed in patients with Cr allergy over time. METHODS: A questionnaire study was performed among 172 adult dermatitis patients with Cr allergy and 587 age- and sex-matched dermatitis patients without Cr allergy. A questionnaire was sent to all dermatitis patients patch tested from 2003 to 2018 in August 2019. RESULTS: The overall response rate was 61.2% (759/1241). Patients with Cr allergy were still more commonly affected by current foot dermatitis (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.07-7.08) and hand dermatitis (OR 1.98, 95% CI 1.13-3.49) compared with controls diagnosed during 2013 to 2018. The proportion of patients with Cr allergy reporting dermatitis caused by leather exposure did not change during 2003 to 2012 vs 2013 to 2018 (71.0% vs 66.2%, P = .5). Furthermore, estimates on occupational performance and disease severity (eg, current dermatitis), number of anatomical locations with dermatitis, worst-case dermatitis, and effect on work were similar in patients with Cr allergy for 2003 to 2012 vs 2013 to 2018. CONCLUSION: No immediate sign of improvement was found in patients with Cr allergy concerning severity of disease and dermatitis from leather exposures 5 years after adoption of the regulation against hexavalent Cr in leather. The regulation may have to be revised for better protection of those already sensitized.

The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Miner studies and radiological protection against radon.

Fundamental estimates of radon-associated health risk have been provided by epidemiological studies of miners. In total, approximately 15 studies have been conducted worldwide since the 1960s. These results have contributed directly to radiological protection against radon. The present article summarises the main results, with a focus on analyses of miners exposed more recently, estimates of radon lifetime attributable risk, and interaction between radon and smoking. The potential for the upcoming Pooled Uranium Miner Analysis project to further improve our knowledge is discussed.

Treating the Disease, Not the Symptom: Beyond NSAIDs.

Mitigating inflammation is clearly important in cancer prevention and control. Traditionally, pharmaceuticals have taken the lead in this problem. In an attempt to 'head them off at the pass', this Forum takes a hard look at the concept of 'better living through chemicals' and limiting proinflammatory chemicals entering the body.

Novel DNA methylation biomarkers for hexavalent chromium exposure: an epigenome-wide analysis.

Aim: We aimed to identify differential methylation of genes that could illuminate the biological mechanisms of chromium (VI) toxicity in this exposure-control study. Materials & methods: DNA methylation was measured in blood samples collected from electroplating workers and controls using a combination of Infinium Methylation450K Chip and targeted-bisulfite sequencing. QuantiGene assay was used to detect the mRNA expression of differentially methylated genes. Inductively coupled plasma-mass spectrometry was used to quantify metals in blood and urine samples. The cytosine-phosphate-guanine sites methylation and gene expression were confirmed in a human lymphoblastoid cell line. Results & conclusion: A total of 131 differentially methylated cytosine-phosphate-guanine sites were found between exposures and controls. DNA methylation of SEMA4B may serve as a potential biomarker for chromium (VI) exposure.

Understanding mechanisms of cancer initiation and development supports the need for an implementation of primary and secondary cancer prevention.

The burden of cancer is increasing worldwide, with a continuous rise of the annual total cases. Although mortality rates due to cancer are declining in developed countries, the total number of cancer deaths continues to rise due to the increase in the number of aged people. Three main causes of cancer have been described, represented by environmental factors, hereditary factors and random factors related to defects originated during cell replication. The frequency of cancers is very different for the various tissues and there is great debate on the extent of the specific contribution of environmental factors and random factors (due to "bad luck") to cancer development. However, there is consensus that about 50% of all cases of cancer are related to environment and are preventable. Although a part of cancers is related to intrinsic mechanisms non preventable of genetic instability, it is evident that implementation of primary and secondary prevention measures is the only affordable strategy to meet from a medical and economic point of view the tremendous pressure created on healthcare structures by the increased cancer burden. It is time to bypass the paradox of disease prevention: celebrated in principle, resisted in practice.

Can intravesical application of paracetamol benefit the chemotherapy treatment of bladder cancer?

Bladder cancer is one of the most common urogenital tumors. Its prevalence is increasing worldwide, especially men. The cyclooxygenase-2 (COX-2) enzyme has been shown to increase in bladder cancer and has a direct relationship with tumor progression. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the growth of the tumor by inhibiting the COX-2 enzyme. NSAIDs have other effects unrelated to COX that provide anticancer properties. Also, similar to NSAIDs, anticancer effects of paracetamol have been shown in many studies. Therefore we hypothesize intravesical paracetamol application will have beneficial effects in the treatment of non-muscle invasive bladder cancer (NMBIC).

"Nondetected": The Politics of Measurement of Asbestos in Talc, 1971-1976.

The recent lawsuits against Johnson & Johnson have raised the issue of what and when talcum powder manufacturers knew about the presence of asbestos in their products and what they did or did not do to protect the public. Low-level exposure to asbestos in talc is said to result in either mesothelioma or ovarian cancer. Johnson & Johnson has claimed that there was "no detectable asbestos" in their products and that any possible incidental presence was too small to act as a carcinogen. But what exactly does "nondetected" mean? Here, we examine the historical development of the argument that asbestos in talcum powder was "nondetected." We use a unique set of historical documents from the early 1970s, when low-level pollution of talc with asbestos consumed the cosmetics industry. We trace the debate over the Food and Drug Administration's efforts to guarantee that talc was up to 99.99% free of chrysotile and 99.9% free of amphibole asbestos. Cosmetic talc powder manufacturers, through their trade association, pressed for a less stringent methodology and adopted the term "nondetected" rather than "asbestos-free" as a term of art.

Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression.

PURPOSE: A 'risk reversal' has been observed for several human carcinogens following cessation of exposure, but it is unclear whether it also exists for asbestos-related mesothelioma. METHODS: We conducted a systematic review of the literature and identified nine studies that reported information on risk of mesothelioma after cessation of asbestos exposure, and performed a meta-regression based on random effects models. As comparison we analyzed results on lung cancer risk from four of these studies. RESULTS: A total of six risk estimates from five studies were included in the meta-analysis. The summary relative risk (RR) of mesothelioma for 10-year interval since cessation of exposure was 1.02 [95% confidence interval (CI) 0.87-1.19; p-heterogeneity 0.01]. The corresponding RR of lung cancer was 0.91 (95% CI 0.84-0.98). CONCLUSIONS: This analysis provides evidence that the risk of mesothelioma does not decrease after cessation of asbestos exposure, while lung cancer risk does.

A Compendium of Mutational Signatures of Environmental Agents.

Whole-genome-sequencing (WGS) of human tumors has revealed distinct mutation patterns that hint at the causative origins of cancer. We examined mutational signatures in 324 WGS human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. Additionally, six agents produced double-substitution signatures and eight produced indel signatures. Investigating mutation asymmetries across genome topography revealed fully functional mismatch and transcription-coupled repair pathways. DNA damage induced by environmental mutagens can be resolved by disparate repair and/or replicative pathways, resulting in an assortment of signature outcomes even for a single agent. This compendium of experimentally induced mutational signatures permits further exploration of roles of environmental agents in cancer etiology and underscores how human stem cell DNA is directly vulnerable to environmental agents. VIDEO ABSTRACT.

Environmental risk factors for cancer - review paper.

The cancerous process is result of disturbed cell function. This is due to the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which leads to genetic instability. It is difficult to assess the validity of individual aetiological factors, but it can be concluded that interaction of various risk factors has the largest contribution to the cancer development. Environmental, exogenous and endogenous factors as well as individual factors, including genetic predisposition contribute to the development of cancer. Epidemiological research on the development of malignant tumors has focused over the years on the determinants of environmental and genetic factors of cancer incidence and mortality rate. According to current state of knowledge, 80-90% of malignant tumors are caused by external environmental factors (carcinogens). Epidemiological studies have proved that the main factors responsible for the development of malignant neoplasia among humans are environmental factors arising from human behaviour. It has been confirmed that smoking, excessive alcohol consumption, diet, and reproductive behaviour are important for the development of malignant neoplasia in the human population. According to the World Health Organization, in 2020 we may expect about 10 million deaths, including 7-8 million in the developing countries, while this number in the developed countries will not change and will be 2-3 million. The aim this study was systematization of knowledge concerning the risk factors of malignant tumours and supplementing them with the latest research results.

Systematic review: the etiology of esophageal squamous cell carcinoma in low-income settings.

INTRODUCTION: Esophageal carcinoma causes over 380 000 deaths per year, ranking sixth worldwide in mortality amongst all malignancies. Globally, the squamous cell subtype is most common and accounts for 80% of esophageal cancers. Nonetheless, esophageal squamous cell carcinoma is much more poorly understood than esophageal adenocarcinoma, including what is driving such high prevalences, why it often presents in young patients, and shows such marked geographical delineations Areas covered: The current literature was searched for articles focusing on aetiopathogenesis of squamous cell esophageal carcinoma via a systematic review, particularly in low-resource settings. This was supplemented by papers of interest known to the authors. Expert commentary: Current putative mechanisms include polycyclic aromatic hydrocarbons, nitrosamines, acetaldehyde, cyclo-oxygenase-2 pathways, androgen and their receptor levels, as well as smoking & alcohol, micronutrient deficiencies and diet, mycotoxins, thermal damage, oral hygiene and microbiotal factors, inhaled smoke, viral infections such as HPV, and chronic irritative states. Etiology is likely multifactorial and varies geographically. Though smoking and alcohol play a predominant role in high-income settings, there is strong evidence that mycotoxins, diet and temperature effects may play an under-recognized role in low and middle-income settings.

Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018.

CONTEXT: Bladder cancer (BC) is a significant health problem, and understanding the risk factors for this disease could improve prevention and early detection. OBJECTIVE: To provide a systematic review and summary of novel developments in epidemiology and risk factors for BC. EVIDENCE ACQUISITION: A systematic review of original articles was performed by two pairs of reviewers (M.G.C., I.J., F.E., and K.P.) using PubMed/Medline in December 2017, updated in April 2018. To address our primary objective of reporting contemporary studies, we restricted our search to include studies from the last 5yr. We subdivided our review according to specific risk factors (PICO [Population Intervention Comparator Outcome]). EVIDENCE SYNTHESIS: Our search found 2191 articles, of which 279 full-text manuscripts were included. We separated our manuscripts by the specific risk factor they addressed (PICO). According to GLOBOCAN estimates, there were 430000 new BC cases and 165000 deaths worldwide in 2012. Tobacco smoking and occupational exposure to carcinogens remain the factors with the highest attributable risk. The literature was limited by heterogeneity of data. CONCLUSIONS: Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures. In some populations, incidence rates are declining, which may reflect a decrease in smoking. Standardisation of reporting may help improve epidemiologic evaluation of risk. PATIENT SUMMARY: Bladder cancer is common worldwide, and the main risk factors are tobacco smoking and exposure to certain chemicals in the working and general environments. There is ongoing research to identify and reduce risk factors, as well as to understand the impact of genetics on bladder cancer risk.

The impact of p53 function on the metabolic activation of the carcinogenic air pollutant 3-nitrobenzanthrone and its metabolites 3-aminobenzanthrone and N-hydroxy-3-aminobenzanthrone in human cells.

The tumour suppressor p53, encoded by TP53, is a key player in a wide network of signalling pathways. We investigated its role in the bioactivation of the environmental carcinogen 3-nitrobenzanthrone (3-NBA)found in diesel exhaust and its metabolites 3-aminobenzanthrone (3-ABA) and N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) in a panel of isogenic human colorectal HCT116 cells differing only with respect to their TP53 status [i.e. TP53(+/+), TP53(+/-), TP53(-/-), TP53(R248W/+) or TP53(R248W/-)]. As a measure of metabolic competence, DNA adduct formation was determined using 32P-postlabelling. Wild-type (WT) p53 did not affect the bioactivation of 3-NBA; no difference in DNA adduct formation was observed in TP53(+/+), TP53(+/-) and TP53(-/-) cells. Bioactivation of both metabolites 3-ABA and N-OH-3-ABA on the other hand was WT-TP53 dependent. Lower 3-ABA- and N-OH-3-ABA-DNA adduct levels were found in TP53(+/-) and TP53(-/-) cells compared to TP53(+/+) cells, and p53's impact was attributed to differences in cytochrome P450 (CYP) 1A1 expression for 3-ABA whereas for N-OH-3-ABA, an impact of this tumour suppressor on sulphotransferase (SULT) 1A1/3 expression was detected. Mutant R248W-p53 protein function was similar to or exceeded the ability of WT-p53 in activating 3-NBA and its metabolites, measured as DNA adducts. However, identification of the xenobiotic-metabolising enzyme(s) (XMEs), through which mutant-p53 regulates these responses, proved difficult to decipher. For example, although both mutant cell lines exhibited higher CYP1A1 induction after 3-NBA treatment compared to TP53(+/+) cells, 3-NBA-derived DNA adduct levels were only higher in TP53(R248W/-) cells but not in TP53(R248W/+) cells. Our results show that p53's influence on carcinogen activation depends on the agent studied and thereby on the XMEs that mediate the bioactivation of that particular compound. The phenomenon of p53 regulating CYP1A1 expression in human cells is consistent with other recent findings; however, this is the first study highlighting the impact of p53 on sulphotransferase-mediated (i.e. SULT1A1) carcinogen metabolism in human cells.

Cancer risk assessment for occupational exposure to chromium and nickel in welding fumes from pipeline construction, pressure container manufacturing, and shipyard building in Taiwan.

OBJECTIVE: We assessed the cancer risks resulting from the exposure to chromium, hexavalent chromium (Cr (VI) ), oxidic nickel (Ni), and soluble Ni in welding fumes during pipeline and shipyard construction and pressure container manufacturing in Taiwan. We also determined the roles of welding performance and demographic characteristics during the exposure to Cr and Ni. METHODS: Personal air samples were collected for the analysis of Cr and Ni, and the concentrations of Cr (VI), oxidic Ni, and soluble Ni were quantified. We assessed cancer slope factors for Cr, Cr (VI), oxidic Ni, and soluble Ni, and we used the Incremental Lifetime Cancer Risk model proposed by the United States Environmental Protection Agency to calculate excess risk. RESULTS: The risks of exposure to Cr and Cr (VI) in welding fumes exceeded the acceptable level of occupational exposure (10-3). We ranked the excess cancer risk in three industries in decreasing order as follows: pipeline construction, shipyard construction, and pressure container manufacturing. The most sensitive parameters for the risk assessment were Cr and Ni concentrations. Statistically significant determinants of Cr (VI), oxidic Ni, and soluble Ni concentrations were the following: stainless steel as the base metal and the filler metals of shielded metal arc welding (SMAW) and of gas tungsten arc welding (GTAW). CONCLUSION: The study revealed that welders belong to a high cancer-risk group. Furthermore, we demonstrated the roles of filler metals and stainless steel in exposure to Cr and Ni.